BASAL CELL CARCINOMA AND ITS VARIANTS. !
CARCINOMA BASOCELULAR Y SUS VARIANTES. !
PUBLICADO 2017-ACTUALIZADO 2025
EDITORIAL ESPAÑOL
==================
Hola amigos de la red, DERMAGIC hoy con el apasionante tema:
CARCINOMA BASO CELULAR.
Hace mucho tiempo se creía que este tumor NO se presentaba en
NIÑOS, que NO tenia relación con VIRUS, que era BENIGNO, que que
NO producía METÁSTASIS., que NO tenia relación con la GENÉTICA
(Antígenos HLA).
En esta actualización año 2025, vamos a descifrar estas
incógnitas:
El CARCINOMA BASOCELULAR (CBC) fue descrito por primera vez por el cirujano Irlandés Arthur Jacob en 1827, quien reportó una lesion tipo úlcera peculiar que afectaba el párpado y otras áreas faciales.
Antes de eso, se encuentran indicios ancestrales en papiros de
Egipto, de hace miles de años, donde se hacen referencias a estas
lesiones bajo los nombres "no me toques", por su rechazo a la curación
y recurrencia.
En 1903, el alemán Odon Krompecher (patólogo), hizo la primera descripción microscópica de la lesion, y
propuso el término de "epitelioma basocelular" por su semejanza con
las células basales epidérmicas.
En el transcurso del siglo XX, se clarificó su origen celular y
también se aclaro el comportamiento de la las lesiones, siendo
reconocido como un tumor
"semi-maligno" debido a su lento crecimiento y rara metástasis.
Para 1974, la OMS ratifica el nombre de CARCINOMA o EPITELIOMA BASOCELULAR (CBC).
CARACTERÍSTICAS CLÍNICAS:
La lesion se presenta clínicamente como una lesion nodular perlada o
tipo placa con un borde en rodete, traslucido y perlado con
telangiectasias, la cual puede ulcerarse con el tiempo.
Típicamente la lesion se presenta con mayor frecuencia en zonas
expuestas al sol como cabeza, cuello y rostro, especialmente en
personas blancas y mayores de 60 años.
Este criterio de personas mayores de 60 años, fue aclarado con el tiempo, hoy dia el CARCINOMA BASOCELULAR, se puede presentar en adolescentes, adultos jóvenes e incluso niños, también en personas de color, ciertamente con menor frecuencia.
El crecimiento de las lesiones es lento y localizado, y se ha estimado un tiempo que oscila entre 9 a 11 años para producir metastasis, aun produciendo destrucción importante de los tejidos circundantes, es por ello que se le considera "semi maligno".
El factor de riesgo mas importante es la exposición prolongada a la luz ultravioleta, es decir luz solar: frecuente en personas que trabajan con una
exposición solar excesiva: pescadores agricultores, alpinistas,
deportistas, etc.
CLASIFICACIÓN: (Ver fotos)
CLASIFICACIÓN: (Ver fotos)
El CARCINOMA BASOCELULAR se clasifica según su aspecto clínico y
patron histológico especifico para cada tipo, y de ello depende su
agresividad y manejo terapéutico.
1.) NODULAR:
Es una lesion en forma de nódulo, o papula (al comienzo), elevada con
telagiectasias y aspecto perlado.
2.) EXTENSION SUPERFICIAL: Es una macula que luego evoluciona a placa eritematosa con escamas de borde irregular, la cual se extiende lentamente en forma centrifuga (hacia los lados).
2.) EXTENSION SUPERFICIAL: Es una macula que luego evoluciona a placa eritematosa con escamas de borde irregular, la cual se extiende lentamente en forma centrifuga (hacia los lados).
3.) MORFEIFORME:
(esclerodermiforme o atrófico): Se presenta como una placa endurecida
al tacto, algo deprimida (hundida), de aspecto cicatricial, color
pardo, infiltrada, siendo mas agresivo que los anteriores.
4.) ULCERADO: La lesion típica es una ulcera con costras; por lo general esta
variante es la evolución crónica de todos los CARCINOMAS
BASOCELULARES, es decir con el tiempo tienden a ulcerarse si no son
tratados a tiempo.
5.) PIGMENTADO: La lesion es una placa similar al CBC clásico, pero el borde es hiper-pigmentado, incluso toda la lesion puede presentarse pigmentada.
6.) HIPERPIGMENTADO DE PINKUS: con pigmentación oscura, puede parecer un melanoma.
El epitelioma O CARCINOMA BASOCELULAR DE PINKUS, también se le conoce
con el nombre de
"FIBROEPITELIOMA DE PINKUS", es una variante poco frecuente del carcinoma basocelular (CBC), que
presenta una clínica y características histopatológicas
distintivas.
Fue descrito por por Hermann Pinkus, en 1953 por primera vez, quien lo denominó “tumor fibroepitelial premaligno”.
Originalmente fue considerado una entidad separada del CBC, pero hoy dia se acepta que es una variante del CARCINOMA BASOCELULAR.
Fue descrito por por Hermann Pinkus, en 1953 por primera vez, quien lo denominó “tumor fibroepitelial premaligno”.
Originalmente fue considerado una entidad separada del CBC, pero hoy dia se acepta que es una variante del CARCINOMA BASOCELULAR.
Aunque sigue existiendo controversia en el medio científico y
literatura, quienes afirman que la lesion es similar a un
TRICOBLASTOMA, el cual es un tumor benigno que se origina el el folículo
piloso.
Se presenta por lo general en adultos entre
40 y 60 años, sin preferencia marcada por sexo masculino o femenino, y
suele localizarse principalmente en la region lumbo sacra, pero al
igual que el CARCINOMA BASOCELULAR, también se presenta en cabeza,
abdomen, extremidades y raramente en genitales.
Clínicamente hay dos tipos: se presenta como una lesión nodular única, pediculada o sésil, de 1.) color piel, o color rosada, y 2.) la forma pigmentada, también pediculada o tipo placa, con superficie lisa y a veces erosionada, muy similar al CBC PIGMENTADO (ver foto).
Clínicamente hay dos tipos: se presenta como una lesión nodular única, pediculada o sésil, de 1.) color piel, o color rosada, y 2.) la forma pigmentada, también pediculada o tipo placa, con superficie lisa y a veces erosionada, muy similar al CBC PIGMENTADO (ver foto).
La gran diferencia con el CARCINOMA BASOCELULAR PIGMENTADO esta en la
BIOPSIA de la lesion, la cual muestra cordones finos y alargados de
células basaloides que se anastomosan formando una estructura típica
en “panal de abejas”. También se usan marcadores
inmunohistoquímicos para diferenciarlo.
INDICIOS DE MALIGNIZACION DEL CARCINOMA BASOCELULAR:
1.) Crecimiento rápido:
la lesion que por lo generalmente crece lentamente, evoluciona a un
crecimiento "violento", en el curso de meses.
2.) Sangramiento: Por lo general el CBC no sangra, a excepción del tipo ULCERADO.
Sangramientos frecuentes, o con leves traumatismos son señal de una
evolución torpida.
3.) Telangiectasias aumentadas: las telagiectasias que son vasos sanguíneos pequeños que se ven en la
superficie de la lesion y con el tiempo aumentan
considerablemente de tamaño.
4.) Cambios de coloración:
aparecen en la lesion cambios en la tonalidad del color, areas
azuladas, negruzcas, o marrones.
5.) Aparición de placas induradas: con bordes irregulares.
6.) Tiempo de evolución: un CARCINOMA BASOCELULAR con mas de 9 a 11 años de evolución sin
tratamiento, puede dar metastasis o evolucionar a un CARCINOMA
ESPINOCELULAR, el cual si es maligno.
TRATAMIENTOS:
El tratamiento del CARCINOMA BASOCELULAR (CBC) depende principalmente
del riesgo tumoral (bajo vs. alto), la localización de la lesion, el
tamaño, el tipo histológico del tumor, y las características del
paciente.
1. ) TRATAMIENTOS QUIRÚRGICOS:
A.- Escisión quirúrgica estándar con bisturi:
Es el tratamiento de primera línea para la mayoría de los CBC,
especialmente los de bajo riesgo. La tasa de recurrencia es
baja(alrededor del 3-4%). Se recomienda márgenes de mínimo 1 Cm
incluso 2 Cm para lesiones bien delimitadas.
B.- Cirugía micrográfica de Mohs: Este tipo de cirugía se realiza en pabellón quirúrgico y esta indicada en CBC de alto riesgo y recurrentes, localizados en áreas anatómicamente críticas (por ejemplo, la “zona H” facial), o con bordes mal definidos.
B.- Cirugía micrográfica de Mohs: Este tipo de cirugía se realiza en pabellón quirúrgico y esta indicada en CBC de alto riesgo y recurrentes, localizados en áreas anatómicamente críticas (por ejemplo, la “zona H” facial), o con bordes mal definidos.
Consiste en eliminar el tumor principal, el cual se "congela" con
nitrógeno liquido, y se van haciendo cortes, que en el mismo quirófano
un patólogo especializado observa al microscopio, y determina hasta
donde debe llegar la escisión, hasta llegar a piel sana.
Este método permite la evaluación intraoperatoria de los márgenes y
maximiza la conservación del tejido, con tasas de recurrencia
similares o menores a la escisión estándar (bisturí), en tumores
faciales de alto riesgo.
2.) TRATAMIENTOS NO QUIRÚRGICOS:
A.- Electrodesecación y curetaje: Útil en CBC superficiales o nodulares pequeños, en zonas no críticas. La tasa de curación es alta, siendo uno de los métodos mas utilizados en lesiones de pequeño tamaño.
A.- Electrodesecación y curetaje: Útil en CBC superficiales o nodulares pequeños, en zonas no críticas. La tasa de curación es alta, siendo uno de los métodos mas utilizados en lesiones de pequeño tamaño.
B.- Crioterapia:
Menos utilizada, consiste en enfriar el tumor con nitrógeno liquido,
colocando debajo del mismo una aguja que mide la temperatura, hasta
que el punto de enfriamiento alcance una temperatura entre -40 y
-60 grados centígrados.
Esto provoca la destrucción de las células tumorales. La
recurrencia en estos casos esta estimada en un 22%, y los resultados
cosméticos son variables, porque los principales efectos secundarios
son la formación de ampollas (quemaduras por frio), en el sitio del
procedimiento, que pueden dejar secuelas
cicatriciales.
C.- Radioterapia:
Alternativa para pacientes no candidatos a cirugía, especialmente en
tumores localizados en áreas donde la cirugía sería desfigurante o en
pacientes de edad avanzada.
La tasa de recurrencia ES comparables a la cirugía en los CBC de bajo
riesgo, pero los resultados cosméticos pueden ser inferiores. También
existe riesgo de telangiectasias y perdida de la coloración de
la piel (radio dermitis).
D.- Terapia fotodinámica (TFD): Indicada en CBC superficiales y algunos nodulares de bajo riesgo. Utiliza agentes fotosensibilizantes (por ejemplo, metil-aminolevulinato, conocido como MAL) y luz ultravioleta para destruir el tumor.
D.- Terapia fotodinámica (TFD): Indicada en CBC superficiales y algunos nodulares de bajo riesgo. Utiliza agentes fotosensibilizantes (por ejemplo, metil-aminolevulinato, conocido como MAL) y luz ultravioleta para destruir el tumor.
Como funciona este metodo?:
El metil-aminolevulinato (MAL) es un agente fotosensibilizante,
precursor de la protoporfirina IX (PpIX), una sustancia que se acumula
selectivamente en las células tumorales.
Este se aplica tópicamente en las lesiones en forma de crema, se deja unas 2 a 3 horas y
luego se expone a a una luz roja con una longitud de onda entre 570nm
y 670nm. La luz activa
la protoporfirina IX (PpIX) produciendo esta la liberación de
radicales libres que causan la destrucción de las células
tumorales.
Presenta una tasa de recurrencia superior a la cirugía, pero mejores
resultados cosméticos.
3.) TRATAMIENTOS TÓPICOS:
A.- Imiquimod 5%: Aprobado para su uso en los CBC superficiales y algunos nodulares de bajo riesgo. Consiste en aplicar la crema en la lesion durante 6 semanas. La aplicación NO SUELE SER DIARIA, puede ser cada 2 o 3 días. Las tasa de recurrencia es mayor que la cirugía, pero el resultado cosmético es aceptable.
B.-) 5-fluorouracilo: Este medicamento viene en presentación al 2.5% en crema y al 5% en ungüento, y representa una alternativa tópica en los CBC superficiales, con eficacia inferior a la cirugía.
3.) TRATAMIENTOS TÓPICOS:
A.- Imiquimod 5%: Aprobado para su uso en los CBC superficiales y algunos nodulares de bajo riesgo. Consiste en aplicar la crema en la lesion durante 6 semanas. La aplicación NO SUELE SER DIARIA, puede ser cada 2 o 3 días. Las tasa de recurrencia es mayor que la cirugía, pero el resultado cosmético es aceptable.
B.-) 5-fluorouracilo: Este medicamento viene en presentación al 2.5% en crema y al 5% en ungüento, y representa una alternativa tópica en los CBC superficiales, con eficacia inferior a la cirugía.
Se puede utilizar en preparaciones MAGISTRALES e intercalar su uso
con el IMIQUIMOD, bajo el siguiente esquema: 3 días IMIQUIMOD, 2
días 5-FLUORACILO.
4.) TRATAMIENTOS SISTÉMICOS: (enfermedad avanzada):
4.) TRATAMIENTOS SISTÉMICOS: (enfermedad avanzada):
A.- Inhibidores de la vía Hedgehog (Vismodegib, Sonidegib): Aprobados por la FDA en USA. para los CBC localmente avanzados, CBC metastásico en los cuales la cirugía o radioterapia no es la apropiada o indicada.
La vía Hedgehog es una ruta de señalización celular fundamental para el desarrollo
embrionario y el mantenimiento celular. En la mayoría de los
carcinomas basocelulares esta via se encuentra activada, provocando un
crecimiento descontrolado de las células tumorales.
Que son el Vismodegib, Sonidegib, y como actuan:
Son dos medicamentos que vienen en presentación oral, y de primera
línea en estos casos, aunque presentan efectos adversos significativos
como: espasmos musculares, alopecia, molestias gastrointestinales y
alteración sensorial del gusto.
- Vismodegib: cápsulas orales, comúnmente en dosis de 150 mg.
- Sonidegib: cápsulas orales, típicamente en dosis de 200 mg.
Ambos inhibidores actúan bloqueando una proteína llamada
Smoothened (SMO), logrando con esto el bloqueo de de la vía
Hedgehog, por lo tanto se frena la proliferación y crecimiento del
tumor.
B.- Inmunoterapia (Cemiplimab, inhibidor de PD-1):
El Cemiplimab es un anticuerpo monoclonal de tipo inmunoglobulina G4
el cual bloquea el receptor PD-1 (programmed cell death protein 1), en
las células T del sistema inmunitario.
Al presentarse este bloqueo de PD-1
impide que las células tumorales disminuyan o "apaguen" la respuesta
inmune, logrando con ello una reactivación del sistema inmune, para
detectar y destruir las células tumorales o cancerosas.
Esta indicado en pacientes adultos con CARCINOMA BASOCELULAR (CBC) localmente avanzado, o con metastasis, en aquellos que la radioterapia no es viable, o no toleran los inhibidores de la via Hedgehog (Vismodegib, Sonidegib).
Esta inmunoterapia es la primera aprobada para tratar el CBC avanzado en estos contextos.
Administración y dosis:
El Cemiplimab viene en presentación de viales bajo el nombre comercial de LIBTAYO, y se administra mediante infusión intravenosa, generalmente 350 mg cada 3 semanas.
Esta indicado en pacientes adultos con CARCINOMA BASOCELULAR (CBC) localmente avanzado, o con metastasis, en aquellos que la radioterapia no es viable, o no toleran los inhibidores de la via Hedgehog (Vismodegib, Sonidegib).
Esta inmunoterapia es la primera aprobada para tratar el CBC avanzado en estos contextos.
Administración y dosis:
El Cemiplimab viene en presentación de viales bajo el nombre comercial de LIBTAYO, y se administra mediante infusión intravenosa, generalmente 350 mg cada 3 semanas.
El tratamiento puede extenderse hasta casi 2 años (93 semanas)
o hasta que la enfermedad progrese o se presente toxicidad
importante.
Los efectos secundarios mas frecuentes de esta terapia son:
Dolor musculo esquelético, fatiga, picazón, diarrea y erupciones cutáneas, pero también pueden
presentarse efectos severos orgánicos en: intestino, pulmón, riñón,
piel, y glándulas endocrinas, debido a un descontrol inmunitario.
CONCLUSIONES:
El CARCINOMA BASOCELULAR es el CANCER DE PIEL MAS COMÚN, y si se trata
a tiempo el riesgo de malignidad es bajo, puede presentarse tanto en
mujeres como hombres, mayormente adultos.
La exposición al sol es determinante en su aparición, y se ha descrito
en algunos casos asociación con los Antígenos de Histocompatibilidad
(HLA), lo que pudiera indicar predisposición genética.
El tiempo para convertirse en maligno es LARGO, entre 9 y 11 años, pero
si tienes una lesion sospechosa, no tardes en consultar al
medico.
En las 95 referencias los hechos..
Saludos a todos.
Dr, Jose Lapenta.
Dr. José M. Lapenta.
EDITORIAL ENGLISH
=================
Hello friends of the network, DERMAGIC today with the fascinating
topic: BASAL CELL CARCINOMA.
Long ago, it was believed that this tumor did not occur in children, that it was not related to viruses, that it was benign, that it did not produce metastases, that it was not related to genetics (HLA antigens).
In this 2025 update, we will decipher these mysteries:
HISTORY:
BASAL CELL CARCINOMA (BCC) was first described by the Irish surgeon Arthur Jacob in 1827, who reported a peculiar ulcer-like lesion affecting the eyelid and other facial areas.
Before that, ancient evidence can be found in Egyptian papyri dating back thousands of years, where these lesions are referred to as "touch me not," due to their refusal to heal and recurrence.
In 1903, the German pathologist Odon Krompecher made the first microscopic description of the lesion and proposed the term "basal cell epithelioma" due to its resemblance to epidermal basal cells.
During the 20th century, its cellular origin and the behavior of the lesions became clearer, and it was recognized as a "semi-malignant" tumor due to its slow growth and rare metastasis.
In 1974, the WHO ratified the name BASAL CELL CARCINOMA (EPITHELIOMA) (BCC).
Long ago, it was believed that this tumor did not occur in children, that it was not related to viruses, that it was benign, that it did not produce metastases, that it was not related to genetics (HLA antigens).
In this 2025 update, we will decipher these mysteries:
HISTORY:
BASAL CELL CARCINOMA (BCC) was first described by the Irish surgeon Arthur Jacob in 1827, who reported a peculiar ulcer-like lesion affecting the eyelid and other facial areas.
Before that, ancient evidence can be found in Egyptian papyri dating back thousands of years, where these lesions are referred to as "touch me not," due to their refusal to heal and recurrence.
In 1903, the German pathologist Odon Krompecher made the first microscopic description of the lesion and proposed the term "basal cell epithelioma" due to its resemblance to epidermal basal cells.
During the 20th century, its cellular origin and the behavior of the lesions became clearer, and it was recognized as a "semi-malignant" tumor due to its slow growth and rare metastasis.
In 1974, the WHO ratified the name BASAL CELL CARCINOMA (EPITHELIOMA) (BCC).
CLINICAL FEATURES:
The lesion presents clinically as a pearly nodular or plaque-like lesion with a translucent, pearly, ridged border with telangiectasias, which may ulcerate over time.
Typically, the lesion most frequently occurs in sun-exposed areas such as the head, neck, and face, especially in white people and those over 60 years of age.
This criterion for people over 60 years of age was clarified over time. Today, BASAL CELL CARCINOMA can occur in adolescents, young adults, and even children, and also in people of color, although less frequently.
The growth of the lesions is slow and localized, and it has been estimated that it takes 9 to 11 years to metastasize, even though it causes significant destruction of surrounding tissues. This is why it is considered "semi-malignant."
The most important risk factor is prolonged exposure to ultraviolet light, i.e., sunlight: common in people who work with excessive sun exposure: fishermen, farmers, mountaineers, athletes, etc.
CLASSIFICATION: (See photos)
BASAL CELL CARCINOMA is classified according to its clinical appearance and specific histological pattern for each type, which determines its aggressiveness and therapeutic management.
1.) NODULAR: This is a nodule-shaped lesion, or papule (at first), raised with telangiectasias and a pearly appearance.
2.) SUPERFICIAL EXTENSION or SPREAD: This is a macule that later evolves into an erythematous plaque with irregularly bordered scales, which slowly spreads centrifugally (laterally).
3.) MORPHEIFORM (sclerodermiform or atrophic): It presents as a plaque that is hardened to the touch, somewhat depressed (sunken), scarred, brown, infiltrated, and more aggressive than the previous ones.
4.) ULCERATED: The typical lesion is a crusted ulcer; this variant is generally the chronic evolution of all BASAL CELL CARCINOMAS, meaning they tend to ulcerate over time if not treated promptly.
5.) PIGMENTED: The lesion is a plaque similar to classic BCC, but the border is hyperpigmented, and the entire lesion may even appear pigmented.
6.) HYPERPIGMENTED OF PINKUS: With dark pigmentation, it may resemble melanoma.
PINKUS EPITHELIOMA, also known as PINKUS FIBROEPITHELIOMA, is a rare variant of basal cell carcinoma (BCC) with distinctive clinical and histopathological features.
It was first described by Hermann Pinkus in 1953, who called it a "premalignant fibroepithelial tumor."
Originally considered a separate entity from BCC, it is now accepted as a variant of BASAL CELL CARCINOMA.
Although there is still controversy in the scientific community and literature, some claim that the lesion is similar to a TRICHOBLASTOMA, a benign tumor originating in the hair follicle.
It usually presents in adults between 40 and 60 years of age, with no marked preference for male or female sex. It is usually located primarily in the lumbosacral region. However, like BASAL CELL CARCINOMA, it also presents on the head, abdomen, extremities, and rarely on the genitals.
Clinically, there are two types: it presents as a single, pedunculated, or sessile nodular lesion, 1.) skin-colored or pinkish, and 2.) the pigmented form, also pedunculated or plaque-like, with a smooth and sometimes eroded surface, very similar to pigmented BCC (see photo).
The main difference with pigmented basal cell carcinoma is in the biopsy of the lesion, which shows thin, elongated cords of basaloid cells that anastomose, forming a typical "honeycomb" structure. Immunohistochemical markers are also used to differentiate it.
SIGNS OF MALIGNANCY IN BASAL CELL CARCINOMA:
1.) Rapid growth: The lesion, which usually grows slowly, evolves into "violent" growth over the course of months.
2.) Bleeding: BCC usually does not bleed, except for the ulcerated type. Frequent bleeding or bleeding with minor trauma is a sign of a slow progression.
3.) Increased telangiectasias: Telangiectasias are small blood vessels that appear on the surface of the lesion and increase considerably in size over time.
4.) Color changes: Changes in color appear on the lesion, with bluish, blackish, or brown areas.
5.) Appearance of indurated plaques: with irregular borders.
6.) Time of progression: A BASAL CELL CARCINOMA that has progressed for more than 9 to 11 years without treatment can metastasize or evolve into SQUAMOUS CELL CARCINOMA, which is malignant.
TREATMENTS:
Treatment of BASAL CELL CARCINOMA (BCC) depends primarily on tumor risk (low vs. high), the location of the lesion, its size, the histological type of the tumor, and the patient's characteristics.
1.) SURGICAL TREATMENTS:
A. Standard surgical excision with a scalpel: This is the first-line treatment for most BCCs, especially low-risk ones. The recurrence rate is low (around 3-4%). Margins of at least 1 cm, even 2 cm, are recommended for well-defined lesions.
B. Mohs micrographic surgery: This type of surgery is performed in the operating room and is indicated for high-risk and recurrent BCCs located in anatomically critical areas (e.g., the facial "H zone") or with poorly defined borders.
It involves removing the primary tumor, which is "frozen" with liquid nitrogen. Incisions are made in the operating room. A specialized pathologist observes them under a microscope and determines the extent of the excision, reaching healthy skin.
This method allows for intraoperative evaluation of margins and maximizes tissue preservation, with recurrence rates similar to or lower than standard excision (scalpel) in high-risk facial tumors.
2.) NON-SURGICAL TREATMENTS:
A. Electrodesiccation and curettage: Useful for superficial or small nodular BCCs in non-critical areas. The cure rate is high, making it one of the most commonly used methods for small lesions.
B. Cryotherapy: Less commonly used, it consists of cooling the tumor with liquid nitrogen, placing a temperature-measuring needle underneath it until the cooling point reaches a temperature between -40 and -60 degrees Celsius.
This causes the destruction of tumor cells. Recurrence in these cases is estimated at 22%, and cosmetic results are variable, as the main side effects are blistering (frost burns) at the procedure site, which can leave scarring.
C. Radiotherapy: An alternative for patients who are not candidates for surgery, especially for tumors located in areas where surgery would be disfiguring or for elderly patients.
The recurrence rate is comparable to surgery in low-risk BCCs, but cosmetic results may be inferior. There is also a risk of telangiectasias and loss of skin color (radiation dermatitis).
D. Photodynamic therapy (PDT): Indicated for superficial and some low-risk nodular BCCs. It uses photosensitizing agents (e.g., methylaminolevulinate, known as MAL) and ultraviolet light to destroy the tumor.
How does this method work? Methylaminolevulinate (MAL) is a photosensitizing agent and a precursor to protoporphyrin IX (PpIX), a substance that selectively accumulates in tumor cells.
This is applied topically to the lesions in the form of a cream, left on for 2 to 3 hours, and then exposed to red light with a wavelength between 570 and 670 nm. The light activates protoporphyrin IX (PpIX), producing the release of free radicals that cause the destruction of tumor cells.
It has a higher recurrence rate than surgery, but better cosmetic results.
3.) TOPICAL TREATMENTS:
A. Imiquimod 5%: Approved for use in superficial and some low-risk nodular BCCs. It consists of applying the cream to the lesion for 6 weeks. Application is NOT USUALLY DAILY; it can be every 2 or 3 days. The recurrence rate is higher than surgery, but the cosmetic result is acceptable.
B. 5-Fluorouracil: This medication comes in 2.5% cream and 5% ointment forms and represents a topical alternative for superficial BCCs, with lower efficacy than surgery.
It can be used in COMPOUND preparations and alternated with IMIQUIMOD, using the following regimen: 3 days IMIQUIMOD, 2 days 5-FLUOROURACIL.
4.) SYSTEMIC TREATMENTS (advanced disease):
A.- Hedgehog pathway inhibitors (Vismodegib, Sonidegib): Approved by the FDA in the USA for locally advanced BCC and metastatic BCC in which surgery or radiation therapy is not appropriate or indicated.
The Hedgehog pathway is a cell signaling pathway essential for embryonic development and cell maintenance. In most basal cell carcinomas, this pathway is activated, causing uncontrolled tumor cell growth.
What are Vismodegib and Sonidegib, and how do they work?
These are two oral medications and are first-line in these cases, although they present significant adverse effects such as muscle spasms, hair loss, gastrointestinal discomfort, and taste disturbances.
- Vismodegib: oral capsules, usually at a dose of 150 mg.
- Sonidegib: oral capsules, typically at a dose of 200 mg.
Both inhibitors work by blocking a protein called Smoothened (SMO), thereby blocking the Hedgehog pathway and thereby slowing tumor proliferation and growth.
B.- Immunotherapy (Cemiplimab, PD-1 inhibitor):
Cemiplimab is an immunoglobulin G4 monoclonal antibody that blocks the PD-1 (programmed cell death protein 1) receptor on T cells of the immune system.
When this PD-1 blockade occurs, it prevents tumor cells from diminishing or "turning off" the immune response, thereby reactivating the immune system to detect and destroy tumor or cancer cells.
It is indicated for adult patients with locally advanced or METASTATIC CARCINOMA (BCC), in whom radiotherapy is not feasible, or who cannot tolerate Hedgehog pathway inhibitors (Vismodegib, Sonidegib).
This immunotherapy is the first approved for the treatment of advanced BCC in these settings.
Administration and Dosage:
Cemiplimab comes in vials under the brand name LIBTAYO and is administered by intravenous infusion, usually 350 mg every 3 weeks.
Treatment can be extended for up to almost 2 years (93 weeks) or until disease progression or significant toxicity occurs.
The most common side effects of this therapy are musculoskeletal pain, fatigue, itching, diarrhea, and rashes. Severe organ effects may also occur in the intestines, lungs, kidneys, skin, and endocrine glands due to immune imbalance.
CONCLUSIONS:
Basal cell carcinoma is the MOST COMMON SKIN CANCER, and if treated early, the risk of malignancy is low. It can occur in both women and men, mostly adults.
Sun exposure is a determining factor in its development, and in some cases, an association with Histocompatibility Antigens (HLA) has been described, which could indicate a genetic predisposition.
The time to malignancy is long, between 9 and 11 years, but if you have a suspicious lesion, consult your doctor as soon as possible.
A. Imiquimod 5%: Approved for use in superficial and some low-risk nodular BCCs. It consists of applying the cream to the lesion for 6 weeks. Application is NOT USUALLY DAILY; it can be every 2 or 3 days. The recurrence rate is higher than surgery, but the cosmetic result is acceptable.
B. 5-Fluorouracil: This medication comes in 2.5% cream and 5% ointment forms and represents a topical alternative for superficial BCCs, with lower efficacy than surgery.
It can be used in COMPOUND preparations and alternated with IMIQUIMOD, using the following regimen: 3 days IMIQUIMOD, 2 days 5-FLUOROURACIL.
4.) SYSTEMIC TREATMENTS (advanced disease):
A.- Hedgehog pathway inhibitors (Vismodegib, Sonidegib): Approved by the FDA in the USA for locally advanced BCC and metastatic BCC in which surgery or radiation therapy is not appropriate or indicated.
The Hedgehog pathway is a cell signaling pathway essential for embryonic development and cell maintenance. In most basal cell carcinomas, this pathway is activated, causing uncontrolled tumor cell growth.
What are Vismodegib and Sonidegib, and how do they work?
These are two oral medications and are first-line in these cases, although they present significant adverse effects such as muscle spasms, hair loss, gastrointestinal discomfort, and taste disturbances.
- Vismodegib: oral capsules, usually at a dose of 150 mg.
- Sonidegib: oral capsules, typically at a dose of 200 mg.
Both inhibitors work by blocking a protein called Smoothened (SMO), thereby blocking the Hedgehog pathway and thereby slowing tumor proliferation and growth.
B.- Immunotherapy (Cemiplimab, PD-1 inhibitor):
Cemiplimab is an immunoglobulin G4 monoclonal antibody that blocks the PD-1 (programmed cell death protein 1) receptor on T cells of the immune system.
When this PD-1 blockade occurs, it prevents tumor cells from diminishing or "turning off" the immune response, thereby reactivating the immune system to detect and destroy tumor or cancer cells.
It is indicated for adult patients with locally advanced or METASTATIC CARCINOMA (BCC), in whom radiotherapy is not feasible, or who cannot tolerate Hedgehog pathway inhibitors (Vismodegib, Sonidegib).
This immunotherapy is the first approved for the treatment of advanced BCC in these settings.
Administration and Dosage:
Cemiplimab comes in vials under the brand name LIBTAYO and is administered by intravenous infusion, usually 350 mg every 3 weeks.
Treatment can be extended for up to almost 2 years (93 weeks) or until disease progression or significant toxicity occurs.
The most common side effects of this therapy are musculoskeletal pain, fatigue, itching, diarrhea, and rashes. Severe organ effects may also occur in the intestines, lungs, kidneys, skin, and endocrine glands due to immune imbalance.
CONCLUSIONS:
Basal cell carcinoma is the MOST COMMON SKIN CANCER, and if treated early, the risk of malignancy is low. It can occur in both women and men, mostly adults.
Sun exposure is a determining factor in its development, and in some cases, an association with Histocompatibility Antigens (HLA) has been described, which could indicate a genetic predisposition.
The time to malignancy is long, between 9 and 11 years, but if you have a suspicious lesion, consult your doctor as soon as possible.
The facts are in the 95 references...
Greetings to all.
Dr. José Lapenta.
Dr. José M. Lapenta.
==================================================================
REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES
==================================================================
REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES
==================================================================
O.- Photodynamic therapy with methyl-5-aminolevulinate for basal cell
carcinoma: A systematic review and meta-analysis
(2020).
==================================================================
==================================================================
1.) Basal Cell Carcinoma in Children Report of 3 Cases
2.) Papillomaviruses in non-melanoma skin cancer: epidemiological aspects.
3.) Reconstruction of the scalp and cranium using multiple free-tissue transfers following recurrent basal cell carcinoma.
4.) Prognostic value of apoptotic index in cutaneous basal cell carcinomas of head and neck.
5.) Low levels of urokinase plasminogen activator components in basal cell carcinoma of the skin.
6.) Folliculotropic T cells in regressive basal cell carcinoma of skin.
7.) Repeated 5-aminolevulinic acid-based photodynamic therapy following electro-curettage for pigmented basal cell carcinoma.
8.) Sporadic Bazex-Dupre-Christol-like Syndrome: Early Onset Basal Cell Carcinoma, Hypohidrosis, Hypotrichosis, and Prominent Milia.
9.) Reporting basal cell carcinoma: a survey of the attitudes of histopathologists.
10.) Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an italian case-control study.
11.) Collagenolytic and gelatinolytic matrix metalloproteinases and their inhibitors in basal cell carcinoma of skin: comparison with normal skin.
12.) A Cancer-Registry-Assisted Evaluation of the Accuracy of Digital Epiluminescence Microscopy Associated with Clinical Examination ofPigmented Skin Lesions.
13.) Expression of p53 in arsenic-related and sporadic basal cell carcinoma.
14.) Decision support software to help primary care physicians triage skin cancer: a pilot study.
15.) A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study.
16.) Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate.
17.) Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells.
18.) Expression of desmoglein I and plakoglobin in skin carcinomas.
19.) Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous basal and squamous cell carcinomas.
20.) Detoxifying enzyme genotypes and susceptibility to cutaneous malignancy.
21.) Tumors arising in nevus sebaceus: A study of 596 cases.
22.) Liposome-mediated gene transfer into human basal cell carcinoma.
23.) Proliferative Actinic Keratosis: Three Representative Cases.
24.) Diet and basal cell carcinoma of the skin in a prospective cohort of men.
25.) Preliminary observations on the use of topical tazarotene to treat basal-cell carcinoma.
26.)HLA phenotypes and multiple basal cell carcinomas.
27.) Multiple non-melanoma skin cancer: evidence that different MHC genes are associated with different cancers.
28.) HLA DR4 is associated with the development of multiple basal cell carcinomas and malignant melanoma.
29.) Multiple basal cell carcinoma in tropical Australia.
30.) HLA-DR1 is not a sign of poor prognosis for the development of multiple basal cell carcinomas.
31.) Multiple basal cell carcinomas and HLA frequencies in southern Australia.
32.) Expression of human lymphocyte antigen (HLA)-DR on tumor cells in basal cell carcinoma.
33.) Human leukocyte antigen associations in basal cell carcinoma.
34.) Translocation (4; 14) and concomitant inv(14) in a basal cell carcinoma.
35.) Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group [see comments]
36.) Treatment and prevention of basal cell carcinoma with oral isotretinoin.
37.) Chemoprevention of basal cell carcinoma with isotretinoin.
38.) Chemoprevention of skin cancer in xeroderma pigmentosum.
39.) Relative importance of prior basal cell carcinomas, continuing sun
exposure, and circulating T lymphocytes on the development of basal cell carcinoma.
40.) Topical tretinoin in actinic keratosis and basal cell carcinoma.
41.) Margin assessment of selected basal cell carcinomas utilizing laser Doppler velocimetry.
42.) Carbon dioxide laser vaporization and curettage in the treatment of large or multiple superficial basal cell carcinomas.
43.) The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma.
44.) Cryosurgery and topical fluorouracil: a treatment method for widespread basal cell epithelioma in basal cell nevus syndrome.
45.) Selective cytotoxic effect of topical 5-fluorouracil.
46.) Nodular superficial pigmented basal cell epitheliomas.
47.) Metastatic basal cell carcinoma: response to chemotherapy.
48.) Basal cell carcinoma of the vulva with lymph node and skin metastasis--report of a case and review of 20 Japanese cases.
49.) Basal cell carcinoma of the scalp resulting in spine metastasis in a black patient.
50.) Long-term survival following bony metastases from basal cell carcinoma. Report of a case.
51.)Giant basal cell carcinoma with metastasis and secondary amyloidosis: report of case.
52.) Pulmonary metastases from a basal cell carcinoma.
53.) Nonrecurrent primary basal cell carcinoma of the lower extremity with late metastasis.
54.) [Metastatic basal cell carcinoma]
55.) Metastatic basal cell carcinoma: report of twelve cases with a review of the literature [see comments]
56.) Rapid development of metastases from basal cell carcinoma presenting as cranial nerve palsies.
57.) Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study.
58.) Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmstead County, Minnesota.
59.) Does wound healing contribute to the eradication of basal cell carcinoma following curettage and electrodessication?
60.)Does inflammation contribute to the eradication of basal cell carcinoma following curettage and electrodesiccation?
61.) Cryosurgery in dermatology.
62.) [The treatment of basal cell carcinoma patients by dermatologists in Netherland].
63.) [Therapy of non-melanocytic skin tumors].
64.) [High resolution ultrasound imaging: value in treatment of basocellular carcinoma by cryosurgery].
65.) Recurrent basal cell carcinoma treated with cryosurgery.
66.) Fractional cryosurgery. A new technique for basal cell carcinoma of the eyelids and periorbital area.
67.) Long-term follow-up of cryosurgery of basal cell carcinoma of the eyelid.
68.) Five-year results of curettage-cryosurgery of selected large primarybasal cell carcinomas on the nose: an alternative treatment in a geographical area underserved by Mohs' surgery.
69.) Laser microsurgery for superficial T1-T2 basal cell carcinoma of the eyelid margins.
70.)[Use of Nd:YAG laser for treatment of basal-cell carcinomas and some
premalignant conditions].
71.) Laser therapy of skin tumors.
72.) Treatment of superficial basal cell carcinoma and squamous cell carcinoma in situ with a high-energy pulsed carbon dioxide laser.
73.) Prediction of subclinical tumor infiltration in basal cell carcinoma.
74.) Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision.
75.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
76.) Occurrence of human papillomavirus type 16 DNA in cutaneous squamous and basal cell neoplasms.
77.) Basal cell carcinoma of the genitalia.
78.) Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers.
79.)Premalignant lesions and cancers of the skin in the general population:
evaluation of the role of human papillomaviruses.
80.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
============================================================
2.) Papillomaviruses in non-melanoma skin cancer: epidemiological aspects.
3.) Reconstruction of the scalp and cranium using multiple free-tissue transfers following recurrent basal cell carcinoma.
4.) Prognostic value of apoptotic index in cutaneous basal cell carcinomas of head and neck.
5.) Low levels of urokinase plasminogen activator components in basal cell carcinoma of the skin.
6.) Folliculotropic T cells in regressive basal cell carcinoma of skin.
7.) Repeated 5-aminolevulinic acid-based photodynamic therapy following electro-curettage for pigmented basal cell carcinoma.
8.) Sporadic Bazex-Dupre-Christol-like Syndrome: Early Onset Basal Cell Carcinoma, Hypohidrosis, Hypotrichosis, and Prominent Milia.
9.) Reporting basal cell carcinoma: a survey of the attitudes of histopathologists.
10.) Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an italian case-control study.
11.) Collagenolytic and gelatinolytic matrix metalloproteinases and their inhibitors in basal cell carcinoma of skin: comparison with normal skin.
12.) A Cancer-Registry-Assisted Evaluation of the Accuracy of Digital Epiluminescence Microscopy Associated with Clinical Examination ofPigmented Skin Lesions.
13.) Expression of p53 in arsenic-related and sporadic basal cell carcinoma.
14.) Decision support software to help primary care physicians triage skin cancer: a pilot study.
15.) A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study.
16.) Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate.
17.) Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells.
18.) Expression of desmoglein I and plakoglobin in skin carcinomas.
19.) Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous basal and squamous cell carcinomas.
20.) Detoxifying enzyme genotypes and susceptibility to cutaneous malignancy.
21.) Tumors arising in nevus sebaceus: A study of 596 cases.
22.) Liposome-mediated gene transfer into human basal cell carcinoma.
23.) Proliferative Actinic Keratosis: Three Representative Cases.
24.) Diet and basal cell carcinoma of the skin in a prospective cohort of men.
25.) Preliminary observations on the use of topical tazarotene to treat basal-cell carcinoma.
26.)HLA phenotypes and multiple basal cell carcinomas.
27.) Multiple non-melanoma skin cancer: evidence that different MHC genes are associated with different cancers.
28.) HLA DR4 is associated with the development of multiple basal cell carcinomas and malignant melanoma.
29.) Multiple basal cell carcinoma in tropical Australia.
30.) HLA-DR1 is not a sign of poor prognosis for the development of multiple basal cell carcinomas.
31.) Multiple basal cell carcinomas and HLA frequencies in southern Australia.
32.) Expression of human lymphocyte antigen (HLA)-DR on tumor cells in basal cell carcinoma.
33.) Human leukocyte antigen associations in basal cell carcinoma.
34.) Translocation (4; 14) and concomitant inv(14) in a basal cell carcinoma.
35.) Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group [see comments]
36.) Treatment and prevention of basal cell carcinoma with oral isotretinoin.
37.) Chemoprevention of basal cell carcinoma with isotretinoin.
38.) Chemoprevention of skin cancer in xeroderma pigmentosum.
39.) Relative importance of prior basal cell carcinomas, continuing sun
exposure, and circulating T lymphocytes on the development of basal cell carcinoma.
40.) Topical tretinoin in actinic keratosis and basal cell carcinoma.
41.) Margin assessment of selected basal cell carcinomas utilizing laser Doppler velocimetry.
42.) Carbon dioxide laser vaporization and curettage in the treatment of large or multiple superficial basal cell carcinomas.
43.) The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma.
44.) Cryosurgery and topical fluorouracil: a treatment method for widespread basal cell epithelioma in basal cell nevus syndrome.
45.) Selective cytotoxic effect of topical 5-fluorouracil.
46.) Nodular superficial pigmented basal cell epitheliomas.
47.) Metastatic basal cell carcinoma: response to chemotherapy.
48.) Basal cell carcinoma of the vulva with lymph node and skin metastasis--report of a case and review of 20 Japanese cases.
49.) Basal cell carcinoma of the scalp resulting in spine metastasis in a black patient.
50.) Long-term survival following bony metastases from basal cell carcinoma. Report of a case.
51.)Giant basal cell carcinoma with metastasis and secondary amyloidosis: report of case.
52.) Pulmonary metastases from a basal cell carcinoma.
53.) Nonrecurrent primary basal cell carcinoma of the lower extremity with late metastasis.
54.) [Metastatic basal cell carcinoma]
55.) Metastatic basal cell carcinoma: report of twelve cases with a review of the literature [see comments]
56.) Rapid development of metastases from basal cell carcinoma presenting as cranial nerve palsies.
57.) Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study.
58.) Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmstead County, Minnesota.
59.) Does wound healing contribute to the eradication of basal cell carcinoma following curettage and electrodessication?
60.)Does inflammation contribute to the eradication of basal cell carcinoma following curettage and electrodesiccation?
61.) Cryosurgery in dermatology.
62.) [The treatment of basal cell carcinoma patients by dermatologists in Netherland].
63.) [Therapy of non-melanocytic skin tumors].
64.) [High resolution ultrasound imaging: value in treatment of basocellular carcinoma by cryosurgery].
65.) Recurrent basal cell carcinoma treated with cryosurgery.
66.) Fractional cryosurgery. A new technique for basal cell carcinoma of the eyelids and periorbital area.
67.) Long-term follow-up of cryosurgery of basal cell carcinoma of the eyelid.
68.) Five-year results of curettage-cryosurgery of selected large primarybasal cell carcinomas on the nose: an alternative treatment in a geographical area underserved by Mohs' surgery.
69.) Laser microsurgery for superficial T1-T2 basal cell carcinoma of the eyelid margins.
70.)[Use of Nd:YAG laser for treatment of basal-cell carcinomas and some
premalignant conditions].
71.) Laser therapy of skin tumors.
72.) Treatment of superficial basal cell carcinoma and squamous cell carcinoma in situ with a high-energy pulsed carbon dioxide laser.
73.) Prediction of subclinical tumor infiltration in basal cell carcinoma.
74.) Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision.
75.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
76.) Occurrence of human papillomavirus type 16 DNA in cutaneous squamous and basal cell neoplasms.
77.) Basal cell carcinoma of the genitalia.
78.) Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers.
79.)Premalignant lesions and cancers of the skin in the general population:
evaluation of the role of human papillomaviruses.
80.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
============================================================
============================================================
1.) Basal Cell Carcinoma in Children Report of 3 Cases
============================================================
Arch Dermatol. 2000;136:370-372
Benjamin W. LeSueur, BS; Nancy G. Silvis, MD; Ronald C. Hansen, MD
Background The peak incidence of basal cell carcinoma occurs in the seventh decade of life and is rare in children. When found in the pediatric age group, basal cell carcinoma is usually associated with a genetic defect, such as basal cell nevus syndrome, xeroderma pigmentosum, or nevus sebaceus. In areas of intense UV radiation exposure, such as the
southwestern United States, children may be at increased risk of developing this malignancy de novo.
Observations Three children (2 boys, aged 8 and 16 years, and an 11-year-old girl) from Tucson, Ariz, with isolated basal cell carcinoma unassociated with any other disease or syndrome are described.
Conclusions Basal cell carcinoma in children is probably the result of a combination of UV radiation exposure and genetic background. Early recognition in children can prevent extensive tissue destruction and excess scarring after excision. A higher index of suspicion for basal cell carcinoma may also aid in prompt diagnosis of a possible genetic disorder, such as basal cell nevus syndrome.
BASAL CELL carcinoma (BCC) in children is rare. Cases of BCC in the pediatric population have been reported in association with basal cell nevus syndrome,1 xeroderma pigmentosum,2 and nevus sebaceus3 and after high-dose radiotherapy.4 Isolated cases of BCC unrelated to one of these
causes are seldom reported in pediatric patients. Consequently, clinicians often have a low index of suspicion, leading to delay in diagnosis. We report 3 cases of de novo BCC in children who presented to the dermatology clinic at the University of Arizona Medical Center, Tucson. These children
had no known genetic syndromes and had not undergone radiotherapy.
COMMENT
=========
Non melanoma skin cancers are the most common malignant neoplasms in the United States, representing one third of all cancers diagnosed every year.5, 6 Basal cell carcinoma represents 75% of nonmelanoma skin cancers and has an estimated annual incidence of more than 700,000 cases nationally.7, 8 The US average annual incidence of BCC in whites is currently 191 per 100,000 and is increasing at a rate of 3% to 7% per year.7, 9
Ultraviolet radiation exposure is partly responsible for both BCC and squamous cell carcinoma, as evidenced by their increased prevalence after chronic exposure to sunlight and the preponderance of these lesions on sun-damaged skin. Although squamous cell carcinoma is associated with cumulative sun exposure, BCC in younger patients does not show this association.10, 11 D'Errico et al10 report that BCC arising before the age of 40 years corresponds with childhood or recreational sun exposure but does not correlate directly with cumulative sun damage. Thus, in areas of the world where the UV radiation is most intense, such as the Sunbelt in
the United States, childhood sun exposure is at a maximum and younger patients are at a higher risk of developing BCC.
Other factors besides sunlight are reported to influence the development of BCC. Gailani et al11 note a strong association between BCC and the inactivation of a gene at chromosome 9q22, which is thought to be a tumor suppressor. Inactivation of this gene was found in tumor tissue in 68% of BCCs examined and did not correlate directly with sun exposure or age. The cause of this mutation is unknown, but possible factors may include ionizing radiation, arsenicals, and polyaromatic hydrocarbons. Basal cell nevus syndrome and xeroderma pigmentosum represent inherited genetic mutations that predispose those affected to BCC. Patients with basal cell nevus syndrome are found to have a germline mutation on chromosome 9.12
The peak incidence of BCC occurs in the seventh decade of life.13 In the pediatric age group, BCC usually occurs in the setting of a known genetic defect (Table 1). Although uncommon, isolated BCC in children without these conditions has been reported.14-29 Price et al14 described a 17-year-old
boy with a solitary BCC of the nose. The patient had a history of sunburns 1 or 2 times per year since the age of 9 years. His mother had a BCC removed at the age of 44 years. Histologically, the tumor was described as superficial BCC. Scobie and Preston17 described a 4-year-old boy with a BCC of the scalp. The patient presented with a small "cyst" on the occipital
region of the scalp and a family history of skin cancer. The lesion, described histologically as well defined, recurred 8 months after excision. Excision was repeated without recurrence of tumor, based on follow-up 1 year later.17 A 12-year-old boy living in Arizona was described by Comstock et al18 with a BCC on the nose. The lesion had been present since his
nose was scratched by a cat 1 year earlier. The youngest patient with BCC, a 27-month-old infant, was described by Keramidas and Anagnostou.21 In this case, the lesion grew rapidly and ulcerated after a 4-month delay in diagnosis.
It is debatable whether BCC is more aggressive in children. Leffell et al30 defined aggressive-growth BCC as sclerosing, morpheaform, infiltrative, or invasive into nerves. Their retrospective review showed an increased occurrence of aggressive-growth BCC in patients younger than 35 years old compared with older patients. In contrast, Betti et al13 and Dinehart et al16 found no increase in the frequency of the morpheaform pattern in younger patients. All 3 of our patients had histologically less aggressive forms of BCC.
As total incidence rates of BCC continue to rise, childhood cases may become more common. This increase in pediatric BCC may be especially true in areas of high-level UV radiation exposure. The percentage of sunny days during the year, higher altitude, and location closer to the equator may
place children in these areas at increased risk. Early recognition can prevent extensive tissue destruction and scarring after excision and aid in prompt diagnosis of a possible genetic syndrome. We recommend that clinicians have a higher index of suspicion for BCC when evaluating questionable lesions in children.
REFERENCES
============
1. Gorlin RJ, Goltz RW. Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib.
N Engl J Med. 1960;262:908-912. 2.
Leibowitz E, Janniger CK, Schwartz RA, Lambert WC.
Xeroderma pigmentosum. Cutis. 1997;60:75-77, 81-84.
3. Goldstein GD, Whitaker DC, Argenyi ZB, Bardach J. Basal cell carcinoma arising in a sebaceous nevus during childhood.
J Am Acad Dermatol.1988;18:429-430.
4. Garcia-Silva J, Velasco-Benito JA, Pena-Penabad C, Armijo M. Basal cell carcinoma in a girl after cobalt irradiation to the cranium for acute lymphoblastic leukemia: case report and literature review. Pediatr Dermatol.1996;13:54-57.
5. Silverberg E, Lubera JA.
Cancer statistics, 1989. CA Cancer J Clin.1989;39:3-20.
6. Boring CC, Squires TS, Tong T Cancer statistics, 1991. CA Cancer J Clin.1991;41:19-36.
7. Silverberg E, Boring CC, Squires TS. Cancer statistics, 1990. CA Cancer J Clin.1990;40:9-26.
8. Parker SL, Tang T, Bolden S, Wingo PA. Cancer statistics, 1997.
CA Cancer J Clin.1997;47:5-27.
9. Green A. Changing patterns in incidence of nonmelanoma skin cancer. Epithelial Cell Biol.1992;1:47-51.
10. D'Errico M, Calcagnile AS, Corona R, et al. p53 mutations and chromosome instability in basal cell carcinomas
developed at an early or late age. Cancer Res.1997;57:747-752.
11. Gailani MR, Leffell DJ, Zeigler A, Gross EG, Brash DE, Bale AE. Relationship between sunlight exposure and a key genetic alteration in basal cell carcinoma. J Natl Cancer Inst. 1996;88:349-354.
12. Gailani MR, Bale SJ, Leffel DJ, DiGiovanna JJ, Peck GL, Poliak S. Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9. Cell. 1992;69:111-117. MEDLINE
13. Betti R, Inselvini E, Carducci M, Crosti C. Age and site prevalence of histologic subtypes of basal cell carcinomas.
Int J Dermatol. 1995;34:174-176.
14. Price MA, Goldberg LH, Levy ML. Juvenile basal cell carcinoma.
Pediatr Dermatol.1994;11:176-177.
15. Cox NH. Basal cell carcinoma in young adults. Br J Dermatol.1992;127:26-29.
16. Dinehart SM, Dodge R, Stanley WE, Franks HH, Pollack SV. Basal cell carcinoma treated with Mohs surgery: a comparison of 54
younger patients with 1050 older patients. J Dermatol Surg Oncol.1992;18:560-566.
17. Scobie WG, Preston J.
Basal cell carcinoma in children. J R Coll Surg Edinb.1992;37:46-47.
18. Comstock J, Hansen RC, Korc A. Basal cell carcinoma in a 12-year-old boy. Pediatrics.1990;86:460-462.
19. Cullen KW, Bleach NR, Green DM. Juvenile basal cell carcinoma.
Br J Clin Pract.1989;43:419-420.
20. Fliss DM, Hauben DJ, Ben-Meir P, Sion-Vardy N. Solitary basal cell carcinoma in a child. Ann Plast Surg.1989;22:43-46.
21. Keramidas DC, Anagnostou D. Basal cell carcinoma of the lower lid in a 27-month-old child. Z Kinderchir.1987;42:250-251.
22. Rahbari H, Mehregan AH.
Basal cell epithelioma (carcinoma) in children and teenagers. Cancer. 1982;49:350-353.
23. Henriksson C, Eldh J, Hersle K, Suurkula M. Basal cell carcinoma in children: case report. Scand J Plast Reconstr Surg.1981;15:157-158.
24. Hernandez-Perez E.
Basal cell carcinoma in children. Dermatologica.1975;150:311-315.
25. Milstone EB, Helwig EB.
Basal cell carcinoma in children. Arch Dermatol.1973;108:523-527.
26. Coskey RJ, Chow C.
Basal cell epitheliomas in children and young adolescents. Cutis.1973;12:224-226.
27. Botvinick I, Mehregan AH, Weissman F. Morphea-like basal cell epithelioma in a child. Arch Dermatol.1967;95:67-68.
28. Murray JE, Cannon B.
Basal-cell cancer in children and young adults.
N Engl J Med.1960;262:440-443.
29. Sewell RL. Basal cell carcinoma in youth. Arch Surg. 1941;42:909-912.
30. Leffel DJ, Headington JT, Wong DS, Swanson NA. Aggressive-growth basal cell carcinoma in young adults. Arch Dermatol.1991;127:1663-1667.
============================================================
2.) Papillomaviruses in non-melanoma skin cancer: epidemiological aspects.
============================================================
Semin Cancer Biol 1999 Dec;9(6):397-403
Kiviat NB
Department of Pathology, University of Washington, Seattle, WA, 98103,
USA
[Record supplied by publisher]
Worldwide, non-melanoma skin cancers (NMSCs), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are the most commonly diagnosed cancers among Caucasians. It is well established that ultraviolet radiation (UVR) plays a central role in the development of these cancers, and more recently, a role for specific genetic mutations in the pathogenesis of BCC has been identified. The possibility that certain types of HPV, either alone or in conjunction with UVR, may play a role in the pathogenesis of these cancers is suggested by several lines of evidence reviewed below.*9 @2depidemiology / non-melanoma skin cancer / papillomavirus Copyright 2000 Academic Press.
============================================================
3.) Reconstruction of the scalp and cranium using multiple free-tissue transfers following recurrent basal cell carcinoma.
============================================================
J Reconstr Microsurg 2000 Feb;16(2):89-93
Anderson PJ, Ragbir M, Berry RB, McLean NR
Department of Plastic and Reconstructive Surgery, Shotley Bridge General
Hospital, Durham, UK.
It is well-recognised that recurrent disease can occur following surgery
for malignancy in the head and neck region. This is particularly true of
basal cell carcinoma in which recurrences may occur over many years and despite the use of different treatment modalities. Reconstruction of large defects may become increasingly difficult and can be optimally managed by free tissue transfer. The authors report a case of basal cell carcinoma that has required treatment for over 20 years, unique in that on five different occasions, free flaps have been used for reconstruction.
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4.) Prognostic value of apoptotic index in cutaneous basal cell carcinomas of head and neck.
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Oral Oncol 1999 Nov 1;35(6):541-547
Staibano S, Lo Muzio L, Mezza E, Argenziano G, Tornillo L, Pannone G, De
Rosa G
Department of Biomorphological and Functional Sciences, Pathology
Section,
Faculty of Medicine and Surgery, University "Federico II", Naples, Italy
Basal cell carcinoma (BCC) is the most common type of human cancer, often locally invasive, and following a benign clinical course. However, a proportion of BCCs do recur after treatment, causing extensive local tissue destruction, seldom metastasizing. Morphological methods to unequivocally distinguish the aggressive forms of these tumors (BCC2) from the ordinary ones (BCC1) have so far been lacking. Apoptosis, or programmed cell death, is thought to be important for the death of tumor cells in various stages of carcinogenesis. We analyzed the extent of apoptosis in BCCs of head and neck in a morphological, morphometric, and electron-microscopic study, to estabilish on a retrospective basis, the relative frequency of recurrence of tumors showing different apoptotic rates. We found that BCC1 showed lower apoptotic index (AI) than BCC2 [BCC1: AI from 2.03 to 10.45% (mean
value: 5.98%) BCC2: AI from 21.91 up to 43.82% (mean value: 39.82%)]. The morphometric analysis of both BCC1 and BCC2 revealed significant differences between the values concerning nuclear area, length, perimeter, and roundness of the apoptotic cells with respect to the 'viable' neoplastic cells. Electron-microscopy confirmed that the features of morphological apoptotic cells were characteristic of programmed cell death. We hypothesized that low apoptotic rates in BCC1 could be indicative of a good prognosis. In fact, this corresponded to an 'expansive' but not still invasive neoplastic state. In this phase, however, the tumor cells may constitute the target for genetic changes triggered by enviromental physical or chemical mutagenic agents, such as UV rays. BCC2, then, could be the result of newly selected mutated neoplastic cellular clones, with
more aggressive biological behavior. The high apoptotic level found in BCC2 could thus be used as an indirect alarm signal from pathologists. This hypothesis seems to be supported by most of the current data in the literature and by the clinical outcome of BCC2 of our series. In our opinion, routine evaluation of apoptosis in BCCs could be proposed to facilitate their sub-classification, contributing toward the evaluation of the prospective outcome of the individual patients.
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5.) Low levels of urokinase plasminogen activator components in basal cell carcinoma of the skin.
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Int J Cancer 2000 Feb;85(4):457-459
Maguire T, Chin D, Soutar D, Duffy MJ
Department of Surgery, St. Vincent's Hospital, Dublin, Ireland.
Basal cell carcinoma of the skin (BCC) is the most common cancer worldwide. Unlike most other human malignancies, BCCs rarely metastasise. In this investigation, we show that the serine protease urokinase plasminogen activator (u-PA), which is causally involved in metastasis, is expressed at lower levels in BCCs compared to other skin cancers, such as squamous-cell carcinomas (SCCs) or malignant melanomas. Similarly, the u-PA receptor as well as the inhibitor PAI-1 were present at lower levels in BCCs relative to both SCCs and melanomas. In contrast to u-PA, tissue-plasminogen activator, which is not thought to be involved in metastasis, was present at similar levels in the different types of skin lesion investigated. We
conclude that the failure of BCCs to metastasise may at least be partially related to low expression of components of the u-PA system. Copyright 2000 Wiley-Liss, Inc.
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6.) Folliculotropic T cells in regressive basal cell carcinoma of skin.
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Am J Dermatopathol 2000 Feb;22(1):30-3
Lespi PJ, Gregorini SD
Department of Pathology, HIGA Dr Jose Penna, Bahia Blanca, Buenos Aires,
Argentina.
The histologic features of regression may be found in some basal cell carcinomas (BCCs), and it is known that T-cell infiltrates have a significant role in host defense against this tumor. We examined 945 hair follicles (HFs) adjacent to 150 regressing BCCs of skin for the presence of inflammatory infiltrates and compared the results against 315 HFs in 50 samples of normal skin. Focal T-cell infiltrates localized mainly to the
upper portion of the HFs were found in 14.5% of the follicles adjacent to regressing BCCs. A statistically significant increase of inflammation in
HFs was observed in BCCs with active regression compared with BCCs with inactive and mixed regression (P < 0.05). An increase in the number of HFs involved by T lymphocytes was also found in regressing BCCs compared to normal skin ( P < 0.00005). These data suggest that the damage to the follicles is concordant with active regression of BCCs. We speculate that the immune-mediated regression of BCCs is not only specifically directed to the cells of the tumor but may also induce activated lymphocytes with cytotoxic capability to cross react with the follicular epithelium.
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7.) Repeated 5-aminolevulinic acid-based photodynamic therapy following electro-curettage for pigmented basal cell carcinoma.
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J Dermatol 2000 Jan;27(1):10-5
Itoh Y, Henta T, Ninomiya Y, Tajima S, Ishibashi A
Department of Dermatology, National Defense Medical College, Tokorozawa,
Japan.
5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) in the
standard
manner is ineffective for pigmented basal cell carcinoma (pBCC), because
melanin absorbs the photoactivating light interred for protoporphyrin
IX. The objective of this study was to assess the therapeutic outcome of pBCCs with repeated ALA-PDT following removal of pigmentation with electro-curettage. After electro-curettage, 16 pBCCs were treated with a
combination of topical application of 20% ALA in O/W emulsion and topical instillation of 10% ALA solution, followed by photoactivating light. ALA-PDT was performed more than three times. Fourteen of 16 pBCCs showed
CR. Two pBCCs showing PR or NR were excised. Repeated ALA-PDT following electro-curettage was effective for pBCC.
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8.) Sporadic Bazex-Dupre-Christol-like Syndrome: Early Onset Basal Cell Carcinoma, Hypohidrosis, Hypotrichosis, and Prominent Milia.
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Dermatol Surg 2000 Feb;26(2):152-154
Glaessl A, Hohenlautner U, Landthaler M, Vogt T
Department of Dermatology, University of Regensburg, Regensburg,
Germany.
BACKGROUND: We present the case of a 32-year-old woman with a large recurrent multifocal basal cell carcinoma on the scalp. Conspicuous accompanying symptoms were multiple periorbital milia, hypotrichosis of the body and the scalp, and hypohidrosis. The sparse hair of the scalp showed further abnormalities such as pili torti, as well as flattened, irregularly curly hairs. OBJECTIVE: In 1964, Bazex et al. described a syndrome characterized by congenital hypotrichosis, follicular atrophoderma, and basocellular neoplasms that included basal cell nevi and early onset basal cell carcinomas. The Bazex-Dupre-Christol syndrome is a rare X-linked dominant disease. A sporadic occurrence with the typical constellation of these symptoms has not yet been reported. The lack of a positive family history and no signs of follicular atrophoderma argues for a sporadic occurrence of a Bazex-Dupre-Christol-like syndrome. The case reported shares several features with the classic Bazex-Dupre-Christol syndrome. CONCLUSION: Our report documents the necessity to look for early development of basal cell carcinomas in patients who show signs of the epidermal malformations described.
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9.) Reporting basal cell carcinoma: a survey of the attitudes of histopathologists.
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J Clin Pathol 1999 Nov;52(11):867-9
Milroy CJ, Richman PI, Wilson GD, Sanders R
Restoration of Function and Appearance Trust, Mount Vernon Hospital,
Northwood, Middlesex, UK. milroy@graylab.ac.uk
AIMS: To investigate the histopathological reporting of basal cell carcinoma. METHODS: Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). RESULTS: 24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of different classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were differences in methods of processing and reporting biopsies. CONCLUSIONS: There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for
uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer.
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10.) Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an italian case-control study.
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J Am Acad Dermatol 2000 Mar;42(3):446-52
Naldi L, DiLandro A, D'Avanzo B, Parazzini F
[Medline record in process]
BACKGROUND: Despite its frequency, there is a paucity of data on risk factors for basal cell carcinoma. OBJECTIVE: We assessed potential risk factors for basal cell carcinoma in a population from southern Europe. METHODS: This multicenter case-control study involved 528 newly diagnosed cases and 512 controls. RESULTS: In the multivariate analysis, red hair,
lighter colored eyes, high nevus counts on the upper limbs, and the presence of solar lentigines and actinic keratoses were all associated with basal cell carcinoma. The risk of the tumor increased in subjects who reported burning easily and experiencing sunburn episodes before 15 years of age. An association was documented with indices of recreational sun exposure but no clear evidence of exposure-effect relationship was found. No relation was found with occupational sun exposure. Finally, basal cell carcinoma appeared to be significantly associated with a family history of skin tumors, a personal history of tumors other than those on skin, and radiotherapy. CONCLUSION: Genetic and environmental factors appear to be
involved in the onset of basal cell carcinoma.
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11.) Collagenolytic and gelatinolytic matrix metalloproteinases and their inhibitors in basal cell carcinoma of skin: comparison with normal skin.
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Br J Cancer 2000 Feb;82(3):657-65
Varani J, Hattori Y, Chi Y, Schmidt T, Perone P, Zeigler ME, Fader DJ,
Johnson TM
Department of Pathology, The University of Michigan Medical School, Ann
Arbor 48109, USA.
Tissue from 54 histologically-identified basal cell carcinomas of the skin was obtained at surgery and assayed using a combination of functional and immunochemical procedures for matrix metalloproteinases (MMPs) with collagenolytic activity and for MMPs with gelatinolytic activity. Collagenolytic enzymes included MMP-1 (interstitial collagenase), MMP-8 (neutrophil collagenase) and MMP-13 (collagenase-3). Gelatinolytic enzymes included MMP-2 (72-kDa gelatinase A/type IV collagenase) and MMP-9 (92-kDa gelatinase B/type IV collagenase). Inhibitors of MMP activity including tissue inhibitor of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) were
also assessed. All three collagenases and both gelatinases were detected
immunochemically. MMP-1 appeared to be responsible for most of the functional collagenolytic activity while gelatinolytic activity reflected both MMP-2 and MMP-9. MMP inhibitor activity was also present, and appeared, based on immunochemical procedures, to reflect the presence of
TIMP-1 but not TIMP-2. As a group, tumours identified as having aggressive-growth histologic patterns were not distinguishable from basal cell carcinomas with less aggressive-growth histologic patterns. In normal skin, the same MMPs were detected by immunochemical means. However, only
low to undetectable levels of collagenolytic and gelatinolytic activities were present. In contrast, MMP inhibitor activity was comparable to that
seen in tumour tissue. In previous studies we have shown that exposure of normal skin to epidermal growth factor in organ culture induces MMP up-regulation and activation. This treatment concomitantly induces stromal invasion by the epithelium (Varani et al (1995) Am J Pathol 146: 210-217; Zeigler et al (1996b) Invasion Metastasis 16: 11-18). Taken together with these previous data, the present findings allow us to conclude that the same profile of MMP/MMP inhibitors that is associated with stromal invasion in the organ culture model is expressed endogenously in basal cell carcinomas of skin.
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12.) A Cancer-Registry-Assisted Evaluation of the Accuracy of Digital Epiluminescence Microscopy Associated with Clinical Examination of Pigmented Skin Lesions.
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Dermatology 2000;200(1):11-16
Stanganelli I, Serafini M, Bucch L
Skin Cancer Clinic, Center for Cancer Prevention, Department of
Prevention,
Ravenna Health Care District, Ravenna, Italy.
BACKGROUND: The accuracy of digital epiluminescence microscopy (D-ELM) as an adjunct to clinical examination for the diagnosis of pigmented skin lesions (PSLs) has seldom been evaluated. OBJECTIVE: To compare the accuracy of the combined clinical/D-ELM (C/D-ELM) examination with that of the clinical examination alone. METHODS: A total of 3,372 PSLs from 1,556 consecutive patients referred to a skin cancer clinic underwent clinical
examination and a combined C/D-ELM examination. The reference diagnosis was established using the histology report of known surgical excisions plus a cancer-registry-based follow-up (duration 18 months) of benign C/D-ELM diagnoses. The two diagnostic approaches were compared for sensitivity, predictive value and false-positive rate. RESULTS: The series included 55 melanomas and 43 basal cell carcinomas. About 50% of malignant misdiagnosed cases were identified solely through the cancer registry. The C/D-ELM diagnosis showed a greater sensitivity for melanoma <0.76 mm thick (83 vs. 46% for clinical examination alone; ratio, 1.82) and basal cell carcinoma (79 vs. 49%; ratio, 1.62), a greater predictive value for melanoma (81 vs. 53%; ratio, 1.53) and a reduced total false-positive rate (0.3 vs. 0.9%;
ratio, 0.31). CONCLUSION: D-ELM showed a potential to improve the clinical diagnosis of PSL. Copyright (R) 2000 S.Karger AG, Basel
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13.) Expression of p53 in arsenic-related and sporadic basal cell carcinoma.
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Arch Dermatol 2000 Feb;136(2):195-8
Boonchai W, Walsh M, Cummings M, Chenevix-Trench G
The Queensland Institute of Medical Research, University of Queensland,
Brisbane, Australia.
BACKGROUND: The TP53 gene has been shown to have an important role in the genesis of sporadic, presumably mainly sunlight-related, basal cell carcinoma (BCC). However, its role in arsenic-related BCCs is not clear,
although the trivalent form of arsenic has been long recognized as a cause of BCC. Arsenic treatment has been shown to cause hypermethylation of the TP53 gene in lung carcinoma cell lines, but it is not known if this occurs in vivo in arsenic-related BCCs. OBJECTIVE: To compare the immunohistochemical expression of the p53 protein in arsenic-related and
sporadic BCCs to determine if the expression pattern is consistent with gene silencing. SETTING: A research institute and hospital in Australia.
CASES: One hundred seventeen white patients with 121 sporadic BCCs and 21 white patients with 92 arsenic-related BCCs. MAIN OUTCOME MEASURES: The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi2 test. RESULTS: Arsenic-related BCCs express p53 less often and at a lower intensity than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpression of p53 than those from less-exposed areas (P = .004; 2-tailed test). T
he more aggressive subtypes of BCC show a higher level of expression of p53 than the less aggressive forms (P = .04; 2-tailed chi2 test). CONCLUSIONS: These results are consistent with the hypothesis that the TP53 gene is down-regulated by methylation in arsenic-related BCC, particularly those from less-exposed sites. However, an alternative possibility is that mutations in TP53 that stabilize the protein are less common in arsenic-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.
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14.) Decision support software to help primary care physicians triage skin cancer: a pilot study.
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Arch Dermatol 2000 Feb;136(2):187-92
Gerbert B, Bronstone A, Maurer T, Hofmann R, Berger T
Division of Behavioral Sciences, School of Dentistry, University of California, San Francisco 94111, USA. gerbert@itsa.ucsf.edu
OBJECTIVE: To determine whether decision support software can help primary care physicians proficiently triage lesions suggestive of basal cell and squamous cell carcinoma. DESIGN/MEASURES: Physicians selected triage options for 15 digitized images of skin lesions, with and without use of the decision support software.
PARTICIPANTS/SETTINGS:
Twenty primary care physicians practicing in a health maintenance organization or a city health clinic.
INTERVENTION:
Decision support software designed to help physicians arrive at a triage recommendation consisted of a clinical information form, a decision tree, and support features (teaching points, example images, and diagrams).
RESULTS: Without using the decision support software, physicians chose the wrong triage decision 36.7% of the time; using the decision support software, they chose the wrong response only 13.3% of the time. Not using the decision support software, they failed to correctly perform a biopsy on or refer patients with cancerous lesions 22.1% of the time; using the software, they failed to correctly perform a biopsy on or refer patients with cancerous lesions only 3.6% of the time. Physicians scored an average of 3 points (of a possible 15 points) higher when they used the software (signed rank, 101.0; P<.001). They scored an average of 1 point
higher on the 7 cancerous lesions when they used the software (signed rank, 65.5; P<.001).
CONCLUSIONS:
Use of decision support software could improve primary care physicians' triage decisions for lesions suggestive of nonmelanoma skin cancer, and potentially reduce morbidity and health care costs. We are designing a larger study to evaluate the accuracy and utility of the software with patients seen in clinical practice.
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15.) A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study.
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Arch Dermatol 2000 Feb;136(2):179-84
Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard
Medical School, Boston, Mass, USA.
CONTEXT: Although basic research provides plausible mechanisms for benefits of beta carotene supplementation on nonmelanoma skin cancer (NMSC) primarily consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), observational studies are inconsistent. Randomized trial data are limited to 1 trial of secondary prevention that showed no effect of beta carotene on the incidence of NMSC after 5 years.
OBJECTIVE: To test whether supplementation with beta carotene reduces the risk for development of a first NMSC, including BCC and SCC.
DESIGN: Randomized, double-blind, placebo-controlled trial with 12 years of beta carotene supplementation and follow-up. SETTING: Physicians' Health Study in the United States.
PARTICIPANTS: Apparently healthy male physicians aged 40 to 84 years in 1982 (N = 22 071). INTERVENTION: Beta carotene, 50 mg, on alternate days. MAIN OUTCOME MEASURE: Relative risk (RR) and 95% confidence interval (CI) for a first NMSC, BCC, and SCC. RESULTS: After adjusting for age and randomized aspirin assignment, there was no effect of beta carotene on the incidence of a first NMSC (RR, 0.98; 95% CI, 0.92-1.05), BCC (RR, 0.99; 95% CI, 0.92-1.06), or SCC (RR, 0.97; 95% CI, 0.84-1.13). There was also no significant evidence of beneficial or harmful effects of beta carotene on NMSC by smoking status (current, past, or never).
CONCLUSION: This large-scale, randomized, primary prevention trial among apparently healthy well-nourished men indicates that an average of 12 years of supplementation with beta carotene does not affect the development of a first NMSC, including BCC and SCC.
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16.) Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate.
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Cancer Res 2000 Feb 1;60(3):525-9
Henderson BW, Busch TM, Vaughan LA, Frawley NP, Babich D, Sosa TA, Zollo
JD, Dee AS, Cooper MT, Bellnier DA, Greco WR, Oseroff AR
Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New
York 14263, USA.
At high fluence rates in animal models, photodynamic therapy (PDT) can photochemically deplete ambient tumor oxygen through the generation of singlet oxygen, causing acute hypoxia and limiting treatment effectiveness. We report that standard clinical treatment conditions (1 mg/kg Photofrin, light at 630 nm and 150 mW/cm2), which are highly effective for treating
human basal cell carcinomas, significantly diminished tumor oxygen levels during initial light delivery in a majority of carcinomas. Oxygen depletion could be found during at least 40% of the total light dose, but tumors appeared well oxygenated toward the end of treatment. In contrast, initial light delivery at a lower fluence rate of 30 mW/cm2 increased tumor oxygenation in a majority of carcinomas. Laser treatment caused an intensity- and treatment time-dependent increase in tumor temperature. The data suggest that high fluence rate treatment, although effective, may be inefficient.
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17.) Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells.
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Jpn J Cancer Res 1999 Dec;90(12):1351-7
Fujii K, Miyashita T, Takanashi J, Sugita K, Kohno Y, Nishie H, Yasumoto
S,
Furue M, Yamada M
Department of Genetics, National Children's Medical Research Center,
Tokyo.
The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that gamma-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell
lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after gamma-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after gamma-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after gamma-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.
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18.) Expression of desmoglein I and plakoglobin in skin carcinomas.
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J Cutan Pathol 2000 Jan;27(1):24-9
Tada H, Hatoko M, Tanaka A, Kuwahara M, Muramatsu T
Division of Plastic Surgery, Nara Medical University, Japan.
Reduction or absence of cell-cell adhesion molecules has been reported in various carinomas and the abnormal expression of these molecules contributes to the invasive and metastatic behavior of malignant tumor cells. In epidermal keratinocytes, the main cell-cell adhesion systems are adherens junctions and desmosomes. Previous studies have shown that, in skin carcinomas, the decreased expression of E-cadherin, major constitutional glycoprotein of adherens junctions, is associated with the invasive and metastatic ability of the tumor cells. In the present study, we examined the expression of desmoglein I and plakoglobin, the constitutional components of desmosomes, in various skin carcinomas such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), extramammary Paget's disease and Bowen's disease by an immunofluorescence method. In normal human skin, desmoglein I and plakoglobin were strongly expressed in the intercellular space of the epidermis except for the basal cell layer. In BCC and SCC, the expression of desmoglein I and plakoglobin was markedly reduced or absent in tumor cells.
In carcinoma in situ of Paget's disease, compared with the normal epidermal cells surrounding tumor cell nests, the expression of these molecules was reduced in tumor cells. In Paget's disease with dermal infiltration of tumor cells, the expression of these molecules was almost absent throughout the epidermis. In Bowen's disease, the expression of desmoglein I was reduced in the dumping cells and dyskeratotic cells. These results suggest that the expression of desmosomal cadherin is reduced or absent in human skin carcinomas, and that reduction of these molecules may also contribute to the invasiveness and metastasis of skin carcinomas.
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19.) Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous basal and squamous cell carcinomas.
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Anticancer Res 1999 Jul-Aug;19(4B):2929-38
Dumas V, Kanitakis J, Charvat S, Euvrard S, Faure M, Claudy A
INSERM U346, Lyon, France.
BACKGROUND: Basement membrane (BM) antigens and matrix metalloproteinases (MMP) are involved in tumor invasion and metastasis. Basal (BCC) and squamous cell carcinomas (SCC) differ with respect to their biological behavior since the former are only locally aggressive whereas the latter
have a metastatic potential. MATERIALS AND METHODS:
We studied the immunohistochemical expression of several BM antigens and of MMP2 and MMP9, in 13 BCC, 13 SCC, and 8 in situ skin carcinomas. RESULTS: The expression of most BM antigens was reduced in the tumors in comparison with normal skin. Hemidesmosome- and lamina lucida-associated antigens (plectin, NUT2, alpha 6/CD49f and laminin-5) were more decreased in BCC, whereas collagens type VII and IV were more decreased in SCC as compared with BCC; in BCC and SCC both collagens tended to be decreased on the leading edge of invasive tumor masses. In situ carcinomas showed a slightly diminished expression of alpha 6/CD49f integrin, plectin and NUT2. The expression of both MMP2 and MMP9 was increased in SCC as compared with BCC.
CONCLUSION: Our findings further upheld the role of BM antigens and MMPs in the process of tumor aggressiveness. The reduced expression of collagen IV, combined with an increased expression of both MMP2 and MMP9 could account for the increased metastatic potential of SCC vs BCC through an increased invasion of the extracellular matrix and the vascular space.
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20.) Detoxifying enzyme genotypes and susceptibility to cutaneous malignancy.
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Br J Dermatol 2000 Jan;142(1):8-15
Lear JT, Smith AG, Strange RC, Fryer AA
Department of Dermatology, Clinic 6, Bristol Royal Infirmary, Bristol
BS2
8HW, U.K.; *Department of Dermatology, North Staffordshire NHS Trust, Stoke on Trent ST4 7PA, U.K.; Department of Dermatology, Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke on Trent ST4 7PA, U.K.
While ultraviolet (UV) exposure is thought to be a major risk factor for basal cell carcinoma (BCC) and squamous cell carcinoma, more recent research has focused on genetic factors predisposing to these cancers. UV constitutes an oxidative stress with generation of free radicals, leading to lipid and DNA damage and gene mutation. It could therefore be hypothesized that individual ability to deal with these products may be important in cutaneous carcinogenesis. It is clear from recent studies that polymorphisms in detoxifying enzyme genes are important in determining susceptibility to skin cancer.
The magnitude of effect in BCC is similar to that seen with many other previously described risk factors. However, uncertainties exist regarding the phenotypic consequences of some of these polymorphisms and relevant substrates. This review describes the influence of polymorphisms in detoxifying enzymes in determining susceptibility to skin cancer (in particular to BCC) and give a brief overview of the biochemistry of the detoxification process.
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21.) Tumors arising in nevus sebaceus: A study of 596 cases.
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J Am Acad Dermatol 2000 Feb;42(2 Pt 1):263-8
Cribier B, Scrivener Y, Grosshans E
Laboratoire d'Histopathologie Cutanee, Clinique Dermatologique des
Hopitaux
Universitaires de Strasbourg, France.
BACKGROUND: Prophylactic surgical excision of nevus sebaceus (NS) during childhood is often recommended because various neoplasms can occur on NS. The proportion of malignant tumors occurring on NS is highly variable among the published series, and there are controversies on the nature of these neoplasms because many of the previously described basal cell carcinomas could actually be trichoblastomas, which are benign follicular tumors.
OBJECTIVE: We retrospectively analyzed all cases of NS of our collection, excised during the period from 1932 through 1998, and recorded all associated epithelial and nonepithelial changes. We especially differentiated basal cell carcinomas from trichoblastomas by silhouette analysis and examination of the stroma. These findings were analyzed according to gender, age, and localization.
METHODS:
Microscopic analysis of NS by two examiners was performed independently of clinical data.
RESULTS:
A total of 596 cases were included from 290 females and 306 males, mean age 25.4 years (range, 1 month to 87 years); 232 were excised in children younger than 16 years. NSs were located on the scalp in 49.8% of cases. Basal cell carcinomas were found in 5 cases (0.8%, mean age 39.3 years) and benign tumors in 81 cases (13.6%, mean age 46.3 years). Syringocystadenoma papilliferum (n = 30, 15 males, 15 females) and trichoblastoma (n = 28, 7 males, 21 females) were the most frequent benign tumors. NS with associated tumors were located on the scalp in 79% of cases. Only 4 benign tumors (1.7%) and 2 warts were observed in patients younger than 16 years. Various types of epithelial hyperplasia were noted that could not be considered neoplasms, as well as epidermal and apocrine cysts.
CONCLUSION:
The rate of malignant tumors arising on NS was very low and we did not observe such cases in children, who had associated benign tumors in only 1.7% of cases. Benign neoplasms were common and most of them occurred on the scalp; this was not a bias resulting from a longer duration before surgery. Trichoblastoma and not basal cell carcinoma was the most frequent follicular tumor associated with NS and showed a striking female predominance. Most trichoblastomas had previously been misdiagnosed but could actually be easily recognized by typical histologic features. Because most tumors occurred in adults older than 40 years, our study suggests that prophylactic surgery in young children is of uncertain benefit. Clinical follow-up is probably sufficient, and even those cases with clinical changes often proved to be benign tumors or warts.
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22.) Liposome-mediated gene transfer into human basal cell carcinoma.
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Gene Ther 1999 Dec;6(12):1929-35
Hottiger MO, Dam TN, Nickoloff BJ, Johnson TM, Nabel GJ Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, Ann Arbor, MI, USA.
Direct intralesional injection of DNA encoding interferon-alpha2 (IFN-alpha2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%). Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-alpha2 using this method resulted in sustained production of IFN-alpha2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-alpha protein may therefore be applicable to the treatment of cutaneous BCC.
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23.) Proliferative Actinic Keratosis: Three Representative Cases.
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Dermatol Surg 2000 Jan;26(1):65-69
Goldberg LH, Chang JR, Baer SC, Schmidt JD
OBJECTIVE:
This article describes a new subtype of actinic keratosis that exhibits proliferative characteristics both histologically and clinically. We describe three representative cases occuring in the presence of infiltrative squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC).
METHODS: Histories of each lesion in the three cases discussed were obtained. The lesions were removed by Mohs micrographic surgery. Permanent sections, stained with hematoxylin and eosin, were examined and studied under light microscopy.
RESULTS: All three lesions had failed conventional treatment with liquid nitrogen and/or 5-fluorouracil (5-FU). Histologic examination of the lesions revealed sheets of dysplastic cells growing along the basal layer of the epidermis and migrating down hair follicles and sweat ducts. An associated infiltrative SCC and/or BCC was found in each case.
CONCLUSIONS: Proliferative actinic keratosis is resistant to standard therapies because of deep migration of abnormal cells along hair follicles and sweat ducts. It has a strong propensity to develop infiltrative SCC and may occur concomitantly with BCC.
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24.) Diet and basal cell carcinoma of the skin in a prospective cohort of men.
============================================================
Am J Clin Nutr 2000 Jan;71(1):135-41
van Dam RM, Huang Z, Giovannucci E, Rimm EB, Hunter DJ, Colditz GA, Stampfer MJ, Willett WC Departments of Nutrition and Epidemiology, Harvard School of Public Health,
Boston, MA 02115, USA.
BACKGROUND: Low intake of fat and high intake of specific vitamins have been hypothesized to reduce risk of basal cell carcinoma of the skin (BCC).
OBJECTIVE:
Our objective was to examine intakes of fat, antioxidant nutrients, retinol, folate, and vitamin D in relation to risk of BCC. DESIGN: In 1986, diet was assessed by a validated food-frequency questionnaire in 43217 male participants of the Health Professionals Follow-up Study who were 40-75 y of age and free of cancer. During 8 y of follow-up, we ascertained 3190 newly diagnosed cases of BCC.
RESULTS:
Total fat consumption was associated with a lower risk of BCC [relative risk (RR): 0.81; 95% CI: 0.72, 0.90 for the highest compared with the lowest quintile of intake; P for trend < 0.001). Simultaneous modeling of specific fatty acids suggested that this inverse association was limited to monounsaturated fat (RR: 0.79; 95% CI: 0.65, 0.96; P for trend = 0. 02); saturated and polyunsaturated fat were not associated with BCC risk. Folate intake was associated with a slightly higher risk of BCC (RR: 1.19; 95% CI: 1.01, 1.40; P for trend = 0.11), whereas alpha-carotene was associated with a slightly lower risk (RR: 0.88; 95% CI: 0.79, 0.99; P for trend = 0.01). Intakes of long-chain n-3 fatty acids, retinol, vitamin C, vitamin D, or vitamin E were not materially related to BCC risk.
CONCLUSIONS:
These findings do not support the hypothesis that diets low in fat or high in specific vitamins lower risk of BCC.
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25.) Preliminary observations on the use of topical tazarotene to treat basal-cell carcinoma.
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N Engl J Med 1999 Dec 2;341(23):1767-8
Peris K, Fargnoli MC, Chimenti S
Publication Types:
Letter
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============================================================
26.)HLA phenotypes and multiple basal cell carcinomas.
============================================================
SO - Dermatology 1994;189(3):222-4
AU - Rompel R; Petres J; Kaupert K; Mueller-Eckhardt G
PT - JOURNAL ARTICLE
AB - BACKGROUND: Previous investigators noted an association of multiple
basal cell carcinomas (BCC) with certain HLA antigens; however, these findings were contradictory, and the associations were only weak.
OBJECTIVE: The aim of the study was to objectify the previously found associations.
METHODS: Serologic HLA typing for class I and class II antigens was performed in 49 unrelated patients with 5 or more BCCs. RESULTS: HLA-DR4 showed decreased frequencies in the patient group as compared with healthy controls (n = 716). Cw7 was found to be increased in the total group of patients as well as in a subgroup with multiple BCCs of the face (n = 24), while a subgroup with BCCs mainly on the trunk (n = 25) revealed increased frequencies of HLA-A11, -B17, -B22 and -Cw3. However, none of these deviations appeared significant after correction of p values.
CONCLUSION: We conclude that, if at all, the HLA system plays only a minor role in the development of multiple BCCs.
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27.) Multiple non-melanoma skin cancer: evidence that different MHC genes are associated with different cancers.
============================================================
SO - Dermatology 1994;188(2):88-90
AU - Czarnecki D; Tait B; Nicholson I; Lewis A
PT - JOURNAL ARTICLE
AB - HLA DR frequencies of patients with multiple non-melanoma skin cancers were analysed. There were significant differences in the frequencies of HLA DR1, DR4 and DR7 between patients who only had basal cell carcinomas and patients who had both basal and squamous cell carcinomas. There were significant differences in the frequency of HLA DR53 between the two groups. This antigen is in linkage disequilibrium with HLA DR4 and DR7, and it is not possible to distinguish the primary susceptibility locus.
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28.) HLA DR4 is associated with the development of multiple basal cell carcinomas and malignant melanoma.
============================================================
SO - Dermatology 1993;187(1):16-8
AU - Czarnecki D; Nicholson I; Tait B; Nash C
PT - JOURNAL ARTICLE
AB -
An association between HLA DR4 and the development of multiple basal cell carcinomas (BCC) and malignant melanoma (MM) was detected in southern Australia. There were highly significant differences in HLA DR frequencies between patients with multiple BCCs and MM and matched patients with multiple BCCs only. These findings suggest that hereditary factors associated with the HLA system influence what types of multiple skin cancers people develop.
============================================================
29.) Multiple basal cell carcinoma in tropical Australia.
============================================================
SO - Int J Dermatol 1992 Sep;31(9):635-6
AU - Czarnecki D; Collins N; Chow P; Nicholson I; Tait B
PT - JOURNAL ARTICLE
AB - No association between HLA DR1 and the development of multiple basal cell carcinomas (BCC) was found among patients who had lived at least two-thirds of their lives in the tropics. The percentage of patients with multiple BCCs increased with age; this was different from what has been found in people living in the temperate zone of Australia.
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30.) HLA-DR1 is not a sign of poor prognosis for the development of multiple basal cell carcinomas.
============================================================
SO - J Am Acad Dermatol 1992 May;26(5 Pt 1):717-9
AU - Czarnecki D; Lewis A; Nicholson I; Tait B; Nash C
PT - JOURNAL ARTICLE
AB - BACKGROUND: HLA-DR1 is associated with the development of multiple basal cell carcinomas (BCC). However, the association is weak.
OBJECTIVE: The purpose of our study was to determine whether HLA-DR1 is a marker for susceptibility to the development of many BCCs during a lifetime.
METHODS: Persons with multiple BCCs were placed into two groups: those with less than 10 and those with 20 or more. In addition, the HLA-DR1 frequencies were analyzed. RESULTS: HLA-DR1 was associated with multiple BCCs in the
group with less than 10 BCCs but not with the other group. These patients were significantly younger on average than those with 20 or more BCCs.
CONCLUSION: HLA-DR1 is associated with the development of multiple BCCs at an early age but it is not associated with development of large numbers of BCCs. The amount of UV light a person receives appears to be more important.
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31.) Multiple basal cell carcinomas and HLA frequencies in southern Australia.
============================================================
SO - J Am Acad Dermatol 1991 Apr;24(4):559-61
AU - Czarnecki D; Lewis A; Nicholson I; Tait B
PT - JOURNAL ARTICLE
AB
- An association between HLA-DR1 and the development of multiple basal cell carcinomas was detected in southern Australia. A reduction in HLA-DR4 was found in patients with basal cell carcinoma compared with a local control group. The relative risk for HLA-DR1 was 2.1, which was lower than that for persons in farther countries from the equator.
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32.) Expression of human lymphocyte antigen (HLA)-DR on tumor cells in basal cell carcinoma.
============================================================
SO - J Am Acad Dermatol 1987 Apr;16(4):833-8
AU - Kohchiyama A; Oka D; Ueki H
PT - JOURNAL ARTICLE
AB - Immunohistologic studies of eight patients with basal cell carcinoma were undertaken using a series of monoclonal antibodies. In all of the patients, the majority of dermal infiltrates reacted with OKT3 and OKIa1
(HLA-DR), with a slight predominance of OKT4+ helper/inducer T cells (the mean OKT4/OKT8 ratio was 1.8). Both OKT4+ and OKT8+ cells were seen infiltrating the tumor masses. In addition, in five cases, human lymphocyte antigen (HLA)-DR was demonstrated on some tumor cells close to a vast number of HLA-DR+ infiltrates surrounding the carcinoma, but not on epidermal keratinocytes and tumor cells devoid of the HLA-DR+ infiltrates. A considerable number of OKT6+ dendritic cells were also observed surrounding the carcinoma. Staining with OKB7 and OKM1 revealed negligible reactive cells, and virtually none of the dermal infiltrates reacted with Leu-7 (HNK-1). These findings suggest that in addition to varied immunologically competent cells, expression of HLA-DR antigen on tumor cells may participate in a cellular immune reaction, a defense mechanism against tumor cell proliferation in basal cell carcinoma.
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33.) Human leukocyte antigen associations in basal cell carcinoma.
============================================================
SO - J Am Acad Dermatol 1985 Jun;12(6):997-1000
AU - Myskowski PL; Pollack MS; Schorr E; Dupont B; Safai B
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma is the most common form of skin cancer and is
one in which both host and environmental factors are thought to play a
role in its pathogenesis. For an investigation of the role of human leukocyte antigen (HLA)-associated variations in genetic susceptibility, thirty-one patients with multiple basal cell carcinomas were typed for HLA-A, B, C, and DR antigens. Patients were compared with both local and appropriate ethnic group controls. No statistically significant association with HLA-A, B, or C antigens was noted in any group. However, a significant increase in HLA-DR1 was noted in non-Irish, non-Ashkenazi patients. A tendency toward a decrease in HLA-DR3 was also noted among patients of Irish or Ashkenazi Jewish descent. The role of HLA-associated genetic factors in this form of skin cancer needs further investigation.
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34.) Translocation (4; 14) and concomitant inv(14) in a basal cell carcinoma.
============================================================
SO - Cancer Genet Cytogenet 1991 Oct 15;56(2):177-80
AU - Kawasaki RS; Caldeira LF; Andre FS; Gasques JA; Castilho WH;
Bozola
AR; Thome JA; Tajara EH
PT - JOURNAL ARTICLE
AB - Chromosome analysis of short-term cultures from a basal cell carcinoma was performed. The analyzed karyotypes showed a pseudodiploid clone characterized by a der(4)t(4; 14) (p14; p11) and a concomitant inversion of the same chromosome 4 involved in the t(4; 14) with the breakpoints at p14 and q25.
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35.) Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group [see comments]
============================================================
SO - J Natl Cancer Inst 1992 Mar 4;84(5):328-32
AU - Tangrea JA; Edwards BK; Taylor PR; Hartman AM; Peck GL; Salasche SJ;
Menon PA; Benson PM; Mellette JR; Guill MA; et al
PT - CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
AB - BACKGROUND:
High-dose isotretinoin has been reported to have a prophylactic effect on nonmelanoma skin cancer, although it is associated with significant toxicity. PURPOSE: To test the effectiveness of the long-term administration of low-dose isotretinoin in reducing the occurrence of basal cell carcinoma at a new site in patients with previously treated basal cell carcinomas and to measure the toxicity associated with this regimen, we conducted a clinical trial at eight cancer centers.
METHODS: Nine hundred and eighty-one patients with two or more previously confirmed basal cell carcinomas were randomly assigned to receive either 10 mg of isotretinoin or a placebo daily. Patients were followed for 36 months and monitored at 6-month intervals for skin cancer and toxic effects.
RESULTS: After 36 months of treatment, no statistically significant difference in either the cumulative percent of patients with an occurrence of basal cell carcinoma at a new site or the annual rate of basal cell carcinoma formation existed between patients receiving isotretinoin and those receiving the placebo. Elevated serum triglycerides, hyperostotic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P less than .001).
CONCLUSION: This low-dose regimen of isotretinoin not only is ineffective in reducing the occurrence of basal cell carcinoma at new sites in patients with two or more previously treated basal cell carcinomas but also is associated with significant adverse systemic effects.
IMPLICATION: The toxicity associated with the long-term administration of isotretinoin, even at the low dose used in this trial, must be weighted in planning future prevention trials.
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36.) Treatment and prevention of basal cell carcinoma with oral isotretinoin.
============================================================
SO - J Am Acad Dermatol 1988 Jul;19(1 Pt 2):176-85
AU - Peck GL; Di Giovanna JJ; Sarnoff DS; Gross EG; Butkus D; Olsen TG;
Yoder FW
PT - JOURNAL ARTICLE
AB - Twelve patients with multiple basal cell carcinomas resulting from varying causes were treated with high-dose oral isotretinoin (mean daily dosage: 3.1 mg/kg/day) for a mean of 8 months. Of the 270 tumors monitored in these patients, only 8% underwent complete clinical and histologic regression. All patients developed moderate to severe acute toxicities, leading five patients to withdraw from the study. Retinoid skeletal toxicity was identified in two patients who were examined after long-term therapy. Lower doses of isotretinoin (0.25 to 1.5 mg/kg/day) were ineffective for chemotherapy but demonstrated a chemopreventive effect in a subset of three patients who received these lower doses for 3 to 8 years. Two of these three patients have been observed after discontinuation of therapy. In one patient with a history of arsenic exposure, only one new tumor has appeared in a 27-month posttreatment observation period; in the other patient with the nevoid basal cell carcinoma syndrome, 29 new tumors have appeared within a 13-month period. This suggests that the need for long-term maintenance therapy with isotretinoin for chemoprevention of basal cell carcinoma may depend on the underlying cause of the skin cancers.
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37.) Chemoprevention of basal cell carcinoma with isotretinoin.
============================================================
SO - J Am Acad Dermatol 1982 Apr;6(4 Pt 2 Suppl):815-23
AU - Peck GL; Gross EG; Butkus D; Di Giovanna JJ
PT - JOURNAL ARTICLE AB -
Three patients with multiple basal cell carcinomas, due either to excessive sunlight exposure, the nevoid basal cell carcinoma syndrome, or arsenical insecticide exposure, were treated with oral isotretinoin for 2 1/2 to 4 years. Although higher doses were used initially, approximately 1.5 mg/kg/day was used for long-term therapy in all three patients. Therapeutic effects on existing tumors varied between each patient, and only nine of sixty-five lesions underwent complete clinical regression. No tumors enlarged in two patients; a few tumors enlarged slightly in the third patient, particularly during the later courses of therapy when isotretinoin was given at lower dosage. No new lesions have been observed in any of these three patients. With these encouraging preliminary data, it now may be appropriate to perform larger trials for longer periods of time to determine the usefulness of isotretinoin in the chemoprevention of basal cell carcinoma in patients with multiple tumors.
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38.) Chemoprevention of skin cancer in xeroderma pigmentosum.
============================================================
SO - J Dermatol 1992 Nov;19(11):715-8
AU - Kraemer KH; Di Giovanna JJ; Peck GL
PT - JOURNAL ARTICLE
AB - Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000-fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre-existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13-cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5-fold after the drug was discontinued (New Engl J Med 318: 1633-1637, 1988). Toxicity (cutaneous, triglyceride, liver-function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients.
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39.) Relative importance of prior basal cell carcinomas, continuing sun exposure, and circulating T lymphocytes on the development of basal cell carcinoma.
============================================================
SO - J Invest Dermatol 1992 Aug;99(2):227-31
AU - Robinson JK; Rademaker AW
PT - JOURNAL ARTICLE
AB - This 36-month prospective study of a group of 61 people at high risk to develop multiple basal cell carcinomas (BCC) examined the circulating lymphocyte subsets of the population, patterns of sun exposure, and the longitudinal development of basal cell carcinoma. Sun exposure status was highly correlated with immune status defined by the CD4/CD8 T-lymphocyte ratio. There were significantly more BCC at 18 and 36 months in the 35 patients with high sun exposure and low CD4/CD8 ratio than in the 20 patients with low sun exposure and high CD4/CD8 ratio. A multivariate analysis assessed the relative importance of prior basal cell carcinoma, sun exposure, and immune status on the development of the skin cancer. Basal cell carcinoma developing in the previous 18 months and sun exposure during those 18 months were the first and second most important variables in determining development of basal cell carcinoma during the next 18 months. CD4/CD8 ratio had no additional predictive ability once prior skin cancers and sun exposure were accounted for. A low ratio of CD4/CD8 cells correlated with high sun exposure during the preceding 18 months.
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40.) Topical tretinoin in actinic keratosis and basal cell carcinoma.
============================================================
SO - J Am Acad Dermatol 1986 Oct;15(4 Pt 2):829-35
AU - Peck GL
PT - CLINICAL TRIAL; JOURNAL ARTICLE
AB - In several studies between 1962 and 1978, topical tretinoin was proved capable of producing complete regression of actinic keratosis and basal cell carcinoma. But because its efficacy is not comparable to that of other modalities, topical tretinoin is currently used only as an adjunct to topical 5-fluorouracil in the treatment of actinic keratosis. One recent report found topical tretinoin ineffective in the chemoprevention of actinic keratosis. Although the oral synthetic retinoids isotretinoin and etretinate have been used in the prevention and treatment of cutaneous malignancy, the potential exists for chronic toxicity from the prolonged systemic therapy that appears necessary for maintaining the chemopreventive effect. For this reason, it may be appropriate to study further the preventive as well as therapeutic effects of topical tretinoin and other retinoids for actinic keratosis and skin cancer. If they prove safe and effective, the use of topical retinoids in the prevention and treatment of cutaneous tumors may be the most significant clinical application of these drugs.
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41.) Margin assessment of selected basal cell carcinomas utilizing laser
Doppler velocimetry.
============================================================
SO - Int J Dermatol 1993 Apr;32(4):290-2
AU - Kirsner RS; Haiken M; Garland LD
PT - JOURNAL ARTICLE
AB - BACKGROUND. Basal cell carcinomas (BCC) have increased vasculature, therefore, blood flow within the tumor may be greater than normal surrounding skin. We attempted to detect the difference in blood flow between the tumor and uninvolved surrounding skin utilizing laser doppler velocimetry (LDV).
METHODS. Ten patients with 14 BCC were studied. Using LDV, we calculated the size of the tumor based on margin assessment as predicted by the measured difference in blood flow and compared this size with the clinically predicted size and the size of the defect after Mohs micrographic surgery (MMS).
RESULTS. Clinical evaluation of tumor size prior to MMS did not correlate with the size of the surgical defect after MMS; however, correlation was found between the predicted size of the tumor as determined by LDV and the defect after MMS.
CONCLUSIONS. Tumor size of BCC as predicted by measured differences in blood flow using LDV correlated with the size of the surgical defect after MMS. This suggests that LDV was able to detect the difference in blood flow between the tumor and uninvolved surrounding skin.
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42.) Carbon dioxide laser vaporization and curettage in the treatment of large or multiple superficial basal cell carcinomas.
============================================================
SO - J Dermatol Surg Oncol 1987 Feb;13(2):119-25
AU - Wheeland RG; Bailin PL; Ratz JL; Roenigk RK
PT - JOURNAL ARTICLE
AB - Many of the standard forms of therapy for large or multiple superficial basal cell carcinomas are limited by significant postoperative pain, excessive scarring, and prolonged wound healing time. Combining traditional curettage with carbon dioxide laser vaporization creates a procedure that allows excellent visualization, due to the bloodless surgical field produced by the laser, minimal nonspecific thermal damage, rapid healing, and diminished postoperative pain. In addition, the speed and ease with which this procedure can be performed allow successful treatment of many lesions in a single outpatient session. We wish to report our results using this technique for the treatment of 52 patients with 370 superficial basal cell carcinomas.
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43.) The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma.
============================================================
SO - J Am Acad Dermatol 1992 Nov;27(5 Pt 1):723-8
AU - Orenberg EK; Miller BH; Greenway HT; Koperski JA; Lowe N; Rosen T; Brown DM; Inui M; Korey AG; Luck EE
PT - CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
AB - BACKGROUND:
Basal cell carcinomas (BCCs) are usually treated with ablative procedures. A nonsurgical treatment alternative would be of value in selected patients. OBJECTIVE: We evaluated the safety and efficacy of a new preparation for intralesional sustained-release chemotherapy with MPI 5003, 5-Fluorouracil Therapeutic Implant, for treatment of BCCs.
METHODS:
Two doses of intralesional MPI 5003 (0.25 and 0.5 ml) were compared in a double-blind study of 20 patients with biopsy-proven BCC. One BCC per patient was treated weekly for up to 6 weeks and followed up monthly for 3 months until excisional biopsy for histologic examination. Before excision the cosmetic appearance of the test site was graded.
RESULTS:
Eighty percent of 10 BCCs treated with 0.5 ml of MPI 5003 had histologically confirmed cures as compared with 60% of 10 tumors treated with the lower dose (0.25 ml). Cosmetic assessments before excision were typically good to excellent. No systemic side effects occurred.
CONCLUSION:
Results indicate the potential of MPI 5003 for targeted local chemotherapy for BCC.
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44.) Cryosurgery and topical fluorouracil: a treatment method for widespread basal cell epithelioma in basal cell nevus syndrome.
============================================================
SO - J Dermatol 1993 Aug;20(8):507-13
AU - Tsuji T; Otake N; Nishimura M
PT - JOURNAL ARTICLE
AB - A 58-year-old man with basal cell nevus syndrome had variously sized basal cell epitheliomas (BCEs), mostly of the superficial type, on his chest, back, and lumbar areas. BCEs on the lumbar area were treated with 5-fluorouracil (5-FU) cream which was applied daily under occlusive dressings (ODT). Complete erosion occurred in the center, but not at the periphery of the lesions. In the latter regions, BCE remained. Then cryosurgery (cryo) followed by topical 5-FU (cryo + 5-FU) was tried to treat the peripheral, non-eroded lesions; this caused complete erosions. Biopsy specimens obtained 6 months after epithelization did not show any evidence of recurrence. We also tried either cryo alone or cryo + 5-FU on the chest lesions, and either 5-FU alone or cryo + 5-FU on the abdominal lesions. Cryo alone or 5-FU alone could not clear BCE, but cryo + 5-FU could. These results suggest that the cryo + 5-FU was the most effective of these therapies.
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45.) Selective cytotoxic effect of topical 5-fluorouracil.
============================================================
SO - Arch Dermatol 1983 Sep;119(9):774-83
AU - Dillaha CJ; Jansen GT; Honeycutt WM; Bradford AC
PT - JOURNAL ARTICLE
AB - As an investigative procedure, a hydrophilic ointment containing 20% 5-fluorouracil (5-FU) was applied to the skin of patients with extensive actinic keratoses of the face and neck, for a period of four weeks. This resulted in a selective inflammation, erosion, and disappearance of the keratoses without significant alteration of the normal skin. Transitory adverse reactions included corneal and conjunctival irritations, phototoxic reactions, and erosion of the lower lip border. No evidence of systemic absorption was detected. Only preliminary follow-up observations are available, and no conclusion can be drawn as to the long-term results.
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46.) Nodular superficial pigmented basal cell epitheliomas.
============================================================
SO - Arch Dermatol 1982 Nov;118(11):928-30
AU - Shelley WB; Wood MG
PT - JOURNAL ARTICLE
AB - Eradication of multiple nodules, papules, and plaques of pigmented basal cell epitheliomas of the back of one patient was achieved by nine months of daily treatment with 5% fluorouracil cream. Such topical chemotherapy offers the physician an alternative to surgery and radiation in treating patients who have widespread nodular superficial epitheliomas. The need for a prolonged period of treatment and follow-up is emphasized.
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47.) Metastatic basal cell carcinoma: response to chemotherapy.
============================================================
SO - J Am Acad Dermatol 1990 May;22(5 Pt 2):905-8
AU - Bason MM; Grant-Kels JM; Govil M
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma is a common cutaneous neoplasm that rarely metastasizes. Unfortunately, there is little effective treatment available when metastasis does occur. Therefore potentially promising therapies for metastatic basal cell carcinoma should be reported. We report a case of basal cell carcinoma metastatic to bone, bone marrow, and the pleural cavity in a 51-year-old woman who showed a striking, albeit brief, response to treatment with a combination of cisplatin, bleomycin, methotrexate, and 5-fluorouracil.
============================================================
48.) Basal cell carcinoma of the vulva with lymph node and skin metastasis--report of a case and review of 20 Japanese cases.
============================================================
SO - J Dermatol 1995 Jan;22(1):36-42
AU - Mizushima J; Ohara K
PT - JOURNAL ARTICLE; REVIEW (37 references); REVIEW OF REPORTED CASES
AB - A 79-year-old Japanese woman who had basal cell carcinoma presenting as a large ulcer on her vulva with lymph node and skin metastasis is described. Histological examination revealed that tumor nests with peripheral palisading invaded deeply into the subcutaneous tissue and were accompanied by marked mucinous changes and fibrous reaction. Vascular invasion was also observed. There were inguinal lymph node metastases and two papular skin metastases on her right thigh. The primary tumor and the metastases were excised. The defect was repaired by bilateral gracilis musculo cutaneous flaps and a skin graft. We surveyed the literature and found 20 cases of metastasizing basal cell carcinoma in Japan.
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49.) Basal cell carcinoma of the scalp resulting in spine metastasis in a black patient.
============================================================
SO - J Am Acad Dermatol 1994 Nov;31(5 Pt 2):916-20
AU - Oram Y; Orengo I; Alford E; Green LK; Rosen T; Netscher DT
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma (BCC), the most common skin cancer in the United States, is locally invasive but has a low risk of metastasis. BCC is rare in black patients but, regardless of racial origin, most BCC occurs on sun-exposed areas. We describe a 67-year-old black man with a large BCC on the hairy scalp, a relatively sun-protected area, that metastasized to the spine. To our knowledge, this is the first description of a black patient with development of metastatic BCC on an otherwise normal scalp.
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50.) Long-term survival following bony metastases from basal cell carcinoma. Report of a case.
============================================================
SO - Arch Dermatol 1986 Aug;122(8):912-4
AU - Hartman R; Hartman S; Green N
PT - JOURNAL ARTICLE
AB - A patient with recurrent basal cell carcinoma developed cervical-vertebral and epidural metastases. He received palliative irradiation and had a durable remission for three years. With relapse, he underwent a laminectomy and chemotherapy and remained asymptomatic at 54 months following the diagnosis of bony metastases. To our knowledge, he is the longest reported survivor with bony metastases and is illustrative of the potential survival advantage from palliative therapy.
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51.)Giant basal cell carcinoma with metastasis and secondary amyloidosis: report of case.
============================================================
SO - Acta Derm Venereol 1983;63(6):564-7
AU - Beck HI; Andersen JA; Birkler NE; Ottosen PD
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma of the skin is a slow growing relatively benign tumor usually located on the head and neck. Although rare, metastasis to lymph nodes or parenchymatous organs has been reported previously (1-9). We wish to add another case of metastasizing basal cell carcinoma of the skin, which presented certain unique features only rarely reported (1), namely complicating amyloidosis in the kidneys, the lymph nodes, the spleen and probably in the intestinal canal.
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52.) Pulmonary metastases from a basal cell carcinoma.
============================================================
SO - J Cutan Pathol 1981 Jun;8(3):235-40
AU - Keenan R; Hopkinson JM
PT - JOURNAL ARTICLE
AB - Although basal cell carcinomas are the commonest malignant condition of the skin (Borel 1973) pulmonary metastases are rare; it appears that only 30 authenticated cases have been reported (Sakula 1977). A further case is described of a man aged 64 who presented severe dyspnoea and who for 12 years had harbored an untreated ulcerating lesion of the abdominal wall shown histologically to be a basal cell carcinoma. Chest radiography showed metastatic disease confirmed histologically to be identical to the ulcerating skin lesion. Unfortunately, because of the severe respiratory condition, no definitive treatment was indicated and the patient died of respiratory failure 2 weeks following discharge.
============================================================
53.) Nonrecurrent primary basal cell carcinoma of the lower extremity with late metastasis.
============================================================
SO - J Dermatol Surg Oncol 1994 Jul;20(7):490-3
AU - Siegle RJ; Wood T
PT - JOURNAL ARTICLE
AB - BACKGROUND.
Metastatic basal cell carcinoma (MBCC) is rare, with most cases of head and neck origin and from large multi-recurrent tumors. MBCC is very rare from lower extremities and even more rare from primary tumors that were small and treated without local recurrence.
OBJECTIVE.
This paper presents a case of MBCC in a 78-year-old woman who had previously undergone resection without local recurrence of a small lower extremity basal cell carcinoma.
CONCLUSION.
MBCC can present atypically with site of origin on lower extremities, initial tumor size small, and nonrecurrence of the primary tumor site. The clinician should be aware of this as well as understand that prompt and aggressive surgical therapy to localized metastases may extend survival.
============================================================
54.) [Metastatic basal cell carcinoma]
============================================================
SO - Ann Dermatol Venereol 1993;120(2):135-8
AU - Beaulieu-Lacoste I; Joly P; Ruto F; Thomine E; Fusade T; Chevallier B; Ortoli JC; Lauret P
MC - English Abstract
PT - JOURNAL ARTICLE; REVIEW (16 references); REVIEW OF REPORTED CASES
AB - A case of basal cell carcinoma in a 17-year old male patient complicated, 5 years later, by inguinal and pulmonary metastases is reported. This clinical case raises two problems: the reality of the entity and the long-term follow-up of this type of tumours.
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55.) Metastatic basal cell carcinoma: report of twelve cases with a review of the literature [see comments]
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SO - J Am Acad Dermatol 1991 May;24(5 Pt 1):715-9
AU - Lo JS; Snow SN; Reizner GT; Mohs FE; Larson PO; Hruza GJ
PT - JOURNAL ARTICLE; REVIEW (67 references); REVIEW, TUTORIAL
AB - Metastatic basal cell carcinoma was found in 12 patients at the University of Wisconsin Mohs Surgery Clinic during the period 1936 to 1989. All patients were white men. The time of onset of the primary tumor ranged from childhood to 71 years. Eleven patients had previous treatment for basal cell carcinoma; two patients had received x-ray radiation to the face for teenage acne. The locations of the primary basal cell carcinomas were the face (n = 10), back (n = 1), and arm (n = 1). The primary tumors ranged from 3.6 x 3.0 to 20.0 x 7.0 cm. The interval from onset to the first sign of metastases ranged from 7 to 34 years. In all cases, the primary tumor was histologically identical to the metastatic lesion. Perineural extension of the basal cell carcinoma in the primary lesion was found in five cases. Regional lymph nodes were the most frequent site of metastasis. Treatment consisted of a combination of surgery, radiation, and chemotherapy. Only two patients survived more than 5 years after surgical treatment. One patient has survived 25 years and is still alive.
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56.) Rapid development of metastases from basal cell carcinoma presenting as cranial nerve palsies.
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SO - J Dermatol Surg Oncol 1988 Dec;14(12):1410-2
AU - Ambros RA; Standiford SB; Sobel HJ; Haim A; Mohit-Tabatabai MA
PT - JOURNAL ARTICLE
AB - A case is reported of metastatic basal cell carcinoma presenting with multiple neurologic deficits 20 months after excision of the primary lesion with good local control. Many features associated with the development of metastasis from basal cell carcinoma were not present in this case.
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57.) Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study.
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Acta Derm Venereol 1999 May;79(3):204-6
Soler AM, Warloe T, Tausjo J, Berner A
Photodynamic Out-patient Clinic, Department of Surgical Oncology, The Norwegian Radium Hospital, Oslo.
Fifty-eight patients with 119 nodular (2 mm or more in thickness) basal cell carcinomas successfully treated with photodynamic therapy were included in this 1-year follow-up study. The initial cure rate at 3-6 months was 92% after photodynamic therapy, which included an initial debulking procedure and topical application of dimethylsulphoxide in order to enhance penetration of 5-aminolevulinic acid (20% in cream) to which the lesions were exposed for 3 h prior to exposure to light. At examination 12-26 months (mean 17 months) after treatment 113 lesions (95%) were still in complete response. Six lesions (5%) had recurred, located on the face, scalp and ear. The cosmetic outcome was evaluated as excellent to good in 91%. Microscopic examination of biopsies taken from healed areas in 7 patients did not reveal any sign of damage in 5 and only minor alterations in 2.
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58.) Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmstead County, Minnesota.
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Ophthalmology 1999 Apr;106(4):746-50
Cook BE Jr, Bartley GB
Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
OBJECTIVE: To determine the epidemiologic and clinical characteristics of patients with malignant eyelid tumors in an incidence cohort. DESIGN: Cohort series.
PARTICIPANTS: A computerized retrieval system was used to identify all patients residing in Olmsted County, Minnesota, who had a newly diagnosed malignant eyelid tumor during the 15-year interval from 1976 through 1990. The patients' medical records were reviewed for demographic and clinical data.
INTERVENTION: Surgical excision with frozen-section histopathologic analysis, Mohs' micrographic excision, and electrodesiccation and curettage were the primary methods of treatment.
MAIN OUTCOME MEASURES: Survivorship free of tumor.
RESULTS: The incidence cohort included 174 patients who each had 1 tumor; men and women were equally affected, and all patients were white. Tumors developed most commonly on the lower eyelid (n = 85; 48.9%) and in the medial canthal region (n = 48; 27.6%) but involved the right and left sides with equal frequency. Of the 174 tumors, 158 were basal cell carcinomas (90.8%), 15 were squamous cell carcinomas (8.6%), and 1 (0.6%) was a malignant melanoma. The age- and gender-adjusted incidence rates for basal cell carcinoma, squamous cell carcinoma, and malignant melanoma were 14.35, 1.37, and 0.08 per 100,000 individuals per year, respectively. No cases of sebaceous gland carcinoma were identified. The 5- and 10-year recurrence rates for all tumors on the eyelid were 2% and 3%, respectively. The probability of an unrelated malignancy developing elsewhere in the body was approximately 9% at 5 years and 15% at 10 years.
CONCLUSIONS: Basal cell carcinoma is the most common malignant eyelid tumor in whites. The lower eyelid and medial canthus are the most frequent sites of origin. Men and women are equally affected. Recurrence after surgical excision is uncommon.
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59.) Does wound healing contribute to the eradication of basal cell carcinoma following curettage and electrodessication?
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Dermatol Surg 1999 Mar;25(3):183-7; discussion 187-8
Nouri K, Spencer JM, Taylor JR, Hayag M, DeVoursney J, Shah N Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami Veterans Affairs Medical Center, Florida, USA.
BACKGROUND:
Histologic studies indicate that C&D fails to mechanically remove all the tumor in a percentage of cases that far exceeds the 5-year recurrence rate. This raises the question that if C&D does not mechanically remove the tumor in a significant number of patients, why don't we observe tumor recurrence in most of these patients? Our previous study indicates that inflammation occurring over 1 month following C&D does not clear residual tumor. It may be some other process, requiring more time, that clears the residual tumor. Perhaps the proliferative or maturation phase of wound healing or, alternatively, a slow-acting process such as a low-grade immune response set in motion earlier, clears the residual tumor.
OBJECTIVE:
To test the hypothesis that wound healing and maturation following C&D clear residual tumor that has not mechanically removed by the procedure. METHODS: The frequency of residual BCC detected histologically immediately following C&D was compared with the frequency 3 months after
the C&D, an amount of time in which the maturation phase of wound healing is well under way.
RESULTS:
Twenty-two of 29 primary BCC less than 1 cm in size were tumor-free immediately following the procedure (clearance rate 75.9%). Twelve primary BCC <1 cm were treated by C&D, allowed to heal for 3 months, and then excised and checked histologically. Ten of the twelve BCC were free of tumor, for a clearance rate of 83.3%, which is not a statistically significant difference (p = 0.7187).
CONCLUSION:
By 3 months, the proliferative phase of wound healing is complete, and our study indicates that this phase has no effect on clearing the tumor. The maturation phase is well under way three months following C&D, and no statistically significant
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60.)Does inflammation contribute to the eradication of basal cell carcinoma following curettage and electrodesiccation?
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Dermatol Surg 1997 Aug;23(8):625-30; discussion 630-1
Spencer JM, Tannenbaum A, Sloan L, Amonette RA Division of Dermatology, University of Tennessee, Memphis, USA.
BACKGROUND: Curettage and electrodesiccation (C&D) is probably the technique most frequently utilized by dermatologists to treat basal cell carcinomas (BCC). From histologic studies, it appears C&D does not completely mechanically remove all nests of BCC in a substantial number of cases. Nevertheless, the reported 5-year reoccurrence rate following C&D is significantly less than this histologically observed residual tumor frequency immediately following C&D. Among the multiple possibilities that exist to explain why these residual nests do not appear as recurrent tumor more frequently is the theory that inflammation developing after C&D clears residual tumor.
OBJECTIVE: To test the hypothesis that inflammation developing after C&D clears residual tumor not mechanically removed by the procedure.
METHODS: The frequency of residual BCC detected histologically immediately following C&D was compared with the frequency 1 month after the C&D, an amount of time in which an effect (if any) of inflammation could occur.
RESULTS: Twenty-two of 29 primary BCC < 1 cm treated by C&D were tumor free immediately following the procedure (clearance rate, 75.9%). Eleven of 14 primary BCC < 1 cm treated by C&D then allowed to granulate 1 month before excision and histologic analysis were tumor free, for a clearance rate of 78.6%. Examination of larger tumors immediately following C&D revealed size is a significant variable for clearance rates. Eleven primary BCC > 1 cm but < 2 cm were examined histologically immediately following C&D; only three were tumor free for a clearance rate of 27.3%. Only one of five tumors > 2 cm thus treated was tumor free, for a clearance rate of 20%. Nine recurrent BCC of various sizes were treated by C&D and immediately examined histologically. Two were tumor free for a clearance rate of 22.2%. Two recurrent BCC were allowed to heal 1 month following C&D; one of these was tumor free when excised.
CONCLUSION: For primary BCC < 1 cm, no evidence was found that inflammation occurring over 1 month following C&D clears residual tumor. It was also noted that C&D fails to completely remove tumor in a large majority of primary BCC > 1 cm, and in recurrent BCC.
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61.) Cryosurgery in dermatology.
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Eur J Dermatol 1998 Oct-Nov;8(7):466-74
Zouboulis CC Department of Dermatology, University Medical Center Benjamin Franklin,
The Free University of Berlin, Hindenburgdamm 30, D-12 200, Berlin, Germany.
zoubbere@zedat.fu-berlin.de
The aim of this article is to provide current information on the clinical development of cutaneous cryoreaction and the indications, complications and contraindications of cutaneous cryosurgery. Successful cutaneous cryosurgery requires rapid freezing and slow thawing, minimum tissue temperatures of -25 degrees C to -60 degrees C and, in malignant lesions, repeated freeze-thaw cycles. Frozen tissue reacts with peripheral erythema immediately following thawing, and consequently with oedema, bulla formation, exudation, mummification, and usually heals with a fine atrophic scar within a 4-week period. Cryosurgery is now considered the treatment of choice in hypertrophic scars and keloids, granuloma annulare and capillary haemangioma of the newborn. It also represents a valuable alternative therapy for various skin diseases, including common warts, solar lentigo, actinic keratoses, superficial basal cell carcinoma and Kaposi's sarcoma. Cryosurgery is a safe regimen with only a few adverse effects and contraindications. Pain during and/or shortly after treatment, bulla formation and local oedema are the major, temporary adverse effects; lesional hypopigmentation and/or peripheral hyperpigmentation is the most common by occurring long-term complication.
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62.) [The treatment of basal cell carcinoma patients by dermatologists in Netherland].
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Ned Tijdschr Geneeskd 1998 Jul 4;142(27):1563-7
Thissen MR, Neumann HA, Berretty PJ, Ideler AH Academisch Ziekenhuis, afd. Dermatologie, Maastricht.
OBJECTIVE: To determine the policy of dermatologists practising in the Netherlands in the treatment of basal cell carcinoma. DESIGN: Written enquiry.
SETTING: Catharina Hospital, Eindhoven, the Netherlands.
METHOD: All 293 dermatologists practising in the Netherlands were sent a questionnaire in May 1996 containing 15 questions about diagnosis and treatment of basal cell carcinoma.
RESULTS: Eighteen forms dropped off because of termination of the practice or joint completion in group practices. The response was 76% (208/275). The diagnosis was made usually on the basis of histological examination (71% of the respondents; 84% in a tumour recurrence). Excision was the preferred treatment for all subtypes of basal cell carcinoma; second choices were cryosurgery or curettage/electrocoagulation. Roentgen contact therapy has been practically abandoned. New methods such as photodynamic therapy and immunotherapy are being used only sporadically on an experimental basis. Most dermatologists regarded tumour recurrences as a bigger problem than primary tumours. They attempt to reduce the percentage of recurrences by giving advice about risk factors (sunlight).
CONCLUSION: Too little use is being made of diagnostic biopsy to enable an optimal choice of therapy of basal cell carcinomas, especially in cases of recurrence tumours.
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63.) [Therapy of non-melanocytic skin tumors].
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Ther Umsch 1998 Aug;55(8):515-21
Hafner J Dermatologische Klinik und Poliklinik, Universitatsspital Zurich.
Actinic keratosis on sun-damaged skin are very common in individuals with fair complexion. Management encompasses cryosurgery, tretinoin or 5-fluorouracil-cream. Bowen's disease, however, requires surgical excision or radiotherapy. Basal cell carcinoma and squamous cell carcinoma are the two most common malignant skin tumours in Western Europe. Typically these tumours can be managed either by excision and primary wound closure, by cryosurgery or by radiotherapy.
The method of choice is determined by the type and location of the tumour and the general condition of the patient. For more difficult-to-treat malignant skin tumours surgical resection with histological margin control is required. Mohs' micrographic surgery is a specialized procedure. This method entails to a full work-up of the excisional margins.
The defect is closed only after histological verification of tumour-free surgical margins. Difficult-to-treat tumours are recurrent, sclerodermiform and large (diameter more than 20 mm) basal cell carcinomas. Indications for margin control in squamous cell carcinomas are tumours with more than 20 mm of diameter, with more than 5 mm thickness and with poor histologic differentiation (Broders grade III and IV, desmoplastic squamous cell carcinoma). Therefore, a skin biopsy is often required to plan the optimal treatment of a malignant skin tumour. The collaboration of primary care providers and specialists is beneficial in the management of difficult skin tumours.
Renal transplant recipients under immunosuppression are prone to have squamous cell carcinoma of a more aggressive type. Dermatofibrosarcoma protuberans is another good indication for Mohs' micrographic surgery. A regular follow-up for recurrences or secondary tumours, as well as an effective secondary prevention of sun damage are important for skin cancer patients.
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64.) [High resolution ultrasound imaging: value in treatment of basocellular carcinoma by cryosurgery].
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Ann Dermatol Venereol 1998 Aug;125(8):500-4
Vaillant L, Grognard C, Machet L, Cochelin N, Callens A, Berson M, Aboumrad J, Patat F, Lorette G Service de Dermatologie, CHU Tours.
OBJECTIVE: We conducted a prospective evaluation of the contribution of high-resolution ultrasound imaging prior to cryosurgery for basocellular carcinoma and in search for recurrence.
PATIENTS AND METHODS: All patients seen between 1992 and 1994 at the skin tumor clinic and treated by cryosurgery were included. Ultrasound imaging using 20 MHz prototype was performed prior to cryosurgery and 2 months later.
RESULTS: Among 101 patients treated, 112 basocellular carcinomas were treated by cryosurgery. Ultrasound imaging provided good visualization of the tumor limits in all cases. The ultrasound aspect was anechogenic, often with rare areas of highly dense echoes. The tumor limits described by ultrasound imaging were larger than the clinical limits in 32% of the cases. In 8 of the 16 cases of recurrent tumors, the ultrasound examination revealed the recurrence first. In the other 8 cases, clinical manifestations were confirmed by ultrasonography. In our series, recurrence of basocellular carcinoma was statistically more frequent when the depth of the tumor was 3 mm (ultrasonographic measurement) or when the lateral limits established by ultrasound assessment were greater than the clinical evaluation.
DISCUSSION:
These findings demonstrate that high-resolution ultrasound imaging of basocellular carcinomas prior to cryosurgery: 1) visualizes tumor limits allowing adapted cryosurgery, 2) identifies factors with predictive value for recurrence, 3) can identify recurrences early. Ultrasound imaging of the skin is a useful non-invasive technique for pre- and post-therapeutic assessment of skin tumors and could be a particularly useful tool for "blind" cryosurgery destruction of skin tumors.
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65.) Recurrent basal cell carcinoma treated with cryosurgery.
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J Am Acad Dermatol 1997 Jul;37(1):82-4
Kuflik EG, Gage AA Department of Dermatology, University of Medicine and Dentistry, New
Jersey Medical School, Newark, USA.
BACKGROUND: Although there are reports of cure rates achieved by cryosurgery for primary basal cell carcinomas (BCCs), there are few data on the cryosurgical treatment of recurrent BCCs.
OBJECTIVE: Our purpose was to discuss case selection, cryosurgical management, and results of therapy.
METHODS: Cryosurgery was performed in 54 patients with 56 recurrent BCCs. The treatment consisted of aggressive freezing including an adequate margin of surrounding tissue.
RESULTS: Wound healing was favorable and the cosmetic results were excellent. Two recurrences were found and were referred for Mohs micrographic surgery.
CONCLUSION: We conclude that cryosurgical treatment of selected recurrent BCCs yields results that compare favorably with other methods of treatment.
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66.) Fractional cryosurgery. A new technique for basal cell carcinoma of the eyelids and periorbital area.
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Dermatol Surg 1997 Jun;23(6):475-81
Goncalves JC Department of Dermatology, Hospital Distrital de Santarem, Portugal.
BACKGROUND: Cryosurgery is an established method to treat malignant tumors of the eyelids and periorbital area. Nevertheless, it has been abandoned for tumors greater than 10 mm, because it gives irregular esthetic results and, in some cases, lagophthalmos. OBJECTIVE: To devise a new method for the treatment of such tumors.
METHOD: Fractional cryosurgery is performed in stages: the center of the lesion is frozen, resulting in a reduction of the tumor; this procedure is repeated, as necessary, until the lesion's diameter is smaller than 10 mm; the standard cryosurgical procedure is then carried out.
RESULTS: The treatment of the first 20 basal cell carcinomas with diameters between 10 and 24 mm is described, with excellent clinical and cosmetic results.
CONCLUSION: With fractional cryosurgery, the final scar bears no relation to the size of the original tumor but, instead, corresponds to the size of the lesion preceding the final cryosurgical procedure.
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67.) Long-term follow-up of cryosurgery of basal cell carcinoma of the eyelid.
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J Am Acad Dermatol 1997 May;36(5 Pt 1):742-6
Lindgren G, Larko O Department of Ophthalmology Goteborg University, Sahlgrenska Hospital, Sweden.
BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant tumor of the eyelid and its incidence is increasing. It remains to be established which is the best treatment in terms of safety and cost-effectiveness.
OBJECTIVE: Our purpose was to analyze the long-term treatment results and possible side effects of cryosurgery of eyelid BCC.
METHODS: During the last 14 years 219 patients (222 tumors) treated for eyelid BCC with cryosurgery were followed up prospectively for up to 10 years.
RESULTS: The tumors cleared completely after treatment in all patients with no recurrence observed to date. Ninety-two patients were followed up for 5 years or more. Complications were few and minor. In 26 treated eyelids conjunctival overgrowth was noted.
CONCLUSIONS: We conclude that cryosurgery of BCC of the eyelid has a high cure rate, is cost-effective, and is well tolerated.
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68.) Five-year results of curettage-cryosurgery of selected large primary basal cell carcinomas on the nose: an alternative treatment in a geographical area underserved by Mohs' surgery.
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Br J Dermatol 1997 Feb;136(2):180-3
Nordin P, Larko O, Stenquist B Department of Dermatology, Lundby Hospital, Goteborg, Sweden.
Mohs' micrographic surgery (MMS) is the recommended treatment for large basal cell carcinomas (BCCs) of the nose. This 5-year follow-up study attempts to evaluate whether curettage-cryosurgery (CC) could be an alternative therapy in a country where optimal resources for MMS are lacking. All patients with a primary nasal or perinasal BCC, 10 mm or larger in diameter, were assessed at a skin tumour clinic. Sixty-one BCCs of non-morphoeiform type were treated with CC. Most of the tumour was removed by careful curettage with different sized curettes. The tumour area was then frozen with liquid nitrogen in a double freeze-thaw cycle. Fifty patients were followed for at least 5 years with only one recurrence. The cosmetic result was good or acceptable in all patients. A thorough curettage followed by cryosurgery could be a safe and inexpensive alternative therapy even for large primary non-morphoeiform BCCs of the nose.
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69.) Laser microsurgery for superficial T1-T2 basal cell carcinoma of the eyelid margins.
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Ophthalmology 1997 Jul;104(7):1179-84
Bandieramonte G, Lepera P, Moglia D, Bono A, De Vecchi C, Milani F Division of Surgical Semiotics and Ambulatory Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
BACKGROUND:
Basal cell carcinoma (BCC), the most common malignancy of the eyelid margins, poses therapeutic problems. Surgery, radiation therapy, and cryotherapy are the currently accepted methods for the treatment of this affliction. To verify the technical and clinical effectiveness of the surgical laser method, a specific approach was developed by performing laser-combined procedures under microscopic control.
METHODS:
A series of 26 patients underwent carbon dioxide (CO2) laser microsurgical excision of 27 primary superficial BCCs of the eyelid margins. Eighteen tumors were T1 and 9 were T2. The lesions were located at the lid margins in 18 and at the canthus in 9 cases. The eyelash line was involved in all cases, whereas intermarginal space was involved in 17 cases, without extension to the conjunctival border. Six lesions were in the lacrimal region. Median linear extent of the lesion was 5 mm (range, 4-10 mm). Treatment was performed with the patient under local anesthesia in a Day Hospital regimen. The authors used the microscope-mounted CO2 laser as a scalpel to excise the tumor mass, thus obtaining the specimen for histologic evaluation. The authors treated the deep and lateral resection margins with laser vaporization and left the wound bed to heal by secondary intention.
RESULTS:
No significant complications were observed. As full-thickness eyelid resections were avoided, the authors noted conservation of lid function and cosmetic aspect in all patients. With a median follow-up of 73 months (range, 18-118), only one patient had tumor recurrence after 22 months. This tumor, located at the outer canthus, had a second microsurgical laser excision, and the patient is disease free 51 months after the last treatment.
CONCLUSIONS:
Laser microsurgery appears to be a safe and effective treatment method for primary superficial T1 and T2 BCC of the eyelid margins without conjunctival extension.
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70.)[Use of Nd:YAG laser for treatment of basal-cell carcinomas and some premalignant conditions].
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Przegl Dermatol 1990 Nov-Dec;77(6):385-8
Rubisz-Brzezinska J, Bendkowski W Katedry i Kliniki Dermatologii Sl. AM w Katowicach.
In 51 patients, 29 female and 22 male of average 61 years old, 94 lesions were treated with Nd: YAG laser; 70 basal-cell carcinomas, 9 superficial basal-cell carcinomas, 12 actinic keratosis and 3 cutaneous horns. Size of changes varied from 7 to 24 mm. Quantity of energy used in laser-therapy was dependent on diagnosis, focus size, location and amounted from 50 to 240 J/cm2. Authors are of the opinion that Nd:YAG laser-therapy is a very good method for treatment of skin tumors. Moreover, the advantage of this method is its possibility of a single procedure in the conditions of outpatients clinic.
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71.) Laser therapy of skin tumors.
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Recent Results Cancer Res 1995;139:417-21
Landthaler M, Szeimies RM, Hohenleutner U Department of Dermatology, University of Regensburg, Germany.
Malignant skin tumors can be treated by CO2 laser excision or vaporization, neodymium: yttrium aluminum garnet (Nd:YAG) laser coagulation, and systemic or topical photodynamic therapy (PDT). Possible indications for CO2 laser vaporization include superficial basal cell carcinomas, actinic keratoses, Bowen's disease, actinic cheilitis, and leukoplakias. The Nd:YAG laser may be used for coagulation of basal cell carcinomas, squamous cell carcinomas, Kaposi's sarcoma, and metastatic skin tumors. Systemic and topical PDT is still an experimental modality and is mostly applied for treatment of basal cell carcinomas. However, laser treatment of skin tumors is not yet considered as standard therapy and should be confined to selected patients. Further clinical studies are necessary to determine the role of laser therapy in this special indication.
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72.) Treatment of superficial basal cell carcinoma and squamous cell carcinoma in situ with a high-energy pulsed carbon dioxide laser.
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Arch Dermatol 1998 Oct;134(10):1247-52
Humphreys TR, Malhotra R, Scharf MJ, Marcus SM, Starkus L, Calegari K Department of Medicine, University of Massachusetts Medical Center, Worcester, USA.
BACKGROUND:
High-energy pulsed carbon dioxide (CO2) lasers have been used extensively to resurface wrinkled and photodamaged skin with a low risk of scarring. Results of histological studies demonstrate precise ablation depths in treated skin with minimal thermal damage to underlying tissue. Our objective was to determine if a pulsed CO2 laser could effectively ablate superficial malignant cutaneous neoplasms (superficial multifocal basal cell carcinoma [BCC] and squamous cell carcinoma [SCC] in situ).
OBSERVATIONS: Thirty superficial neoplasms (17 BCCs and 13 SCCs) and their surrounding 3-mm margins were treated with either 2 or 3 passes of a pulsed CO2 laser (500 mJ, 2-4 W) using a 3-mm collimated handpiece.
The treated areas were subsequently excised and evaluated histologically by serial sectioning at 5-micron intervals for residual tumor at the deep and lateral margins. Average patient age was greater for those with SCCs than for those with BCCs (76.5 vs 56.7 years; P = .001). The average tumor thickness of SCC in situ was significantly greater than that of superficial BCC (0.57 vs 0.34 mm; P = .01). All (9 of 9 patients) BCCs were completely ablated with 3 passes, and residual tumor in the deep margins was seen in 5 of 8 patients treated with 2 passes of the pulsed CO2 laser (P = .005). Incomplete vaporization of the SCC depth was seen in 3 of 7 patients treated with 3 passes and in 2 of 6 patients treated with 2 passes. Those SCCs incompletely treated were significantly thicker than those completely ablated (0.65 vs 0.41 mm; P = .01). Positive lateral margins were seen in 1 BCC and 3 SCC specimens.
CONCLUSIONS:
Pulsed CO2 laser treatment can be effective in ablating superficial BCC. Treatment of the neoplasm and a minimum of 4-mm margins with 3 passes (500 mJ, 2-4 W) is recommended for complete vaporization using this laser system. Because 3 passes did not completely ablate all SCC in situ, use of this modality alone is not recommended for treatment of thick or keratotic lesions. No direct comparison of efficacy can be made with other destructive modalities that have not been evaluated with comparably sensitive histological techniques. Further study is needed to establish any cosmetic advantage of pulsed CO2 lasers over other destructive modalities for treatment of superficial malignant neoplasms and long-term cure rates.
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73.) Prediction of subclinical tumor infiltration in basal cell carcinoma.
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J Dermatol Surg Oncol 1991 Jul;17(7):574-8
Breuninger H, Dietz K
Department of Dermatology, University Hospital for Dermatology, Tubingen, Federal Republic of Germany.
Two thousand-sixteen basal cell carcinomas (BCCs) were documented in terms of age, anatomic location, tumor diameter, initial excision depth, safety margin, histologic type, and the position of tumor outgrowths as determined by three-dimensional histologic study of the tumor margins in paraffin sections (micrographic surgery). The extent of each subsequent excision was recorded until tumor-free tissue was reached. The results showed that BCCs have a highly irregular infiltration pattern and a predilection for small, fingerlike outgrowths whose bases occupy 1-30 degrees of the tumor circumference. When superficial extension was expressed mathematically, the resulting exponential functions varied highly significantly (P = .001) according to histologic tumor type and diameter. The resulting curves permitted very precise prediction of the probability of tumor-positive margins (ie, subtotal excision), depending on the safety margin, histologic tumor type, and tumor diameter. For example, the probability of tumor-positive margins after excision of a BCC up to 10 mm in diameter is 30% with a safety margin of 2 mm, 16% with a safety margin of 3 mm, and 5% with a safety margin of 5 mm. The probability of tumor-positive margins for fibrosing primary BCCs 10-20 mm in diameter is 48, 34, and 18% with safety margins of 2, 3, and 5 mm, respectively. Recurrent tumors have a significantly higher probability of positive margins (P = .001) than primary ones. Anatomic location and tumor age affect subclinical extension only indirectly.
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74.) Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision.
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J Dermatol Surg Oncol 1992 Jun;18(6):471-6
Silverman MK, Kopf AW, Bart RS, Grin CM, Levenstein MS Department of Dermatology, New York University School of Medicine.
This is the third report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 588 previously untreated (primary) BCCs removed by surgical excision.
The cumulative 5-year recurrence rate was 4.8%. This is a statistically significant lower recurrence rate (P = .034) than 135 previously treated BCCs that had a re-recurrence rate of 11.6%. For the primary BCCs, multivariate analysis showed that location on the head (P = .010) and being male (P = .004) were independent risk factors for recurrence. The patient's age, the duration of the BCC, its maximum diameter, or the time span (1955-1963, 1964-1972, 1973-1982) in which it was treated did not significantly affect the recurrence rate.
The 5-year recurrence rate for BCCs excised from various anatomic sites were as follows: 1) neck, trunk, and extremities = 0.7%; 2) head--less than 6 mm in diameter = 3.2%; 3) head--6 to 9 mm in diameter = 8.0% (treated since 1964 = 5.2%); and 4) head--10 mm or more in diameter = 9.0%. Surgical excision is a highly effective method for removal of BCCs, and achieved a good to excellent cosmetic outcome in about 85% of the recurrence-free treatment sites.
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75.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
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ARTICLE SOURCE: Arch Dermatol (United States), Jun 1988, 124(6) p930-4
AUTHOR(S): Obalek S; Favre M; Jablonska S; Szymanczyk J; Orth G
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Human papillomavirus-2 genomes were detected by molecular hybridization in two cases of basal cell carcinomas that developed in immunosuppressed individuals. This form of human papillomavirus is usually responsible for common warts in the general population. Although it does not appear to have oncogenic potential, it may be, in some cases, associated with cutaneous malignancy.
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76.) Occurrence of human papillomavirus type 16 DNA in cutaneous squamous and basal cell neoplasms.
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ARTICLE SOURCE: J Am Acad Dermatol (United States), Nov 1990, 23(5 Pt 1) p836-42
AUTHOR(S): Eliezri YD; Silverstein SJ; Nuovo GJ
PUBLICATION TYPE:
JOURNAL ARTICLE
ABSTRACT:
Sixty-eight cutaneous squamous cell neoplasms (in situ and invasive) and 26 basal cell carcinomas from 89 patients were analyzed for DNA sequences homologous to the human papillomavirus (HPV) types found predominantly in the genital tract. Thirty-six (53%) of the squamous cell neoplasms contained HPV DNA as detected by filter or in situ hybridization analysis. The frequency of detection of HPV DNA was dependent on the site of the lesion. Of 40 genital squamous cell neoplasms (penile, vulvar, and perianal), 27 (68%) had detectable HPV DNA. In 25 of these, the HPV type was 16 or HPV-16-related, which was similar to the results for the squamous cell neoplasms of the finger (HPV DNA in 9 of 11 tumors with HPV-16 in seven). None of 16 squamous cell neoplasms from sites other than the genital tract or the finger had detectable HPV DNA. HPV DNA was detected in one of the 26 basal cell carcinomas (4%). We conclude that, for cutaneous epithelial malignancies, HPV-16 is restricted to squamous cell neoplasms of the genital tract and finger. These data are consistent with venereal transmission of HPV-16 to the periungual region and suggests a role for this virus in the evolution of squamous cell carcinoma at this site.
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77.) Basal cell carcinoma of the genitalia.
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Dermatol Surg 1998 Dec;24(12):1361-3
Nehal KS, Levine VJ, Ashinoff R Ronald O. Perelman Department of Dermatology, New York University Medical Center, NY 10016, USA.
BACKGROUND: Basal cell carcinomas (BCC) arising on the genitalia are exceedingly rare with an unclear pathogenesis. OBJECTIVE: To better understand risk factors, tumor characteristics, and the possible role of human papillomavirus (HPV) in the development of BCC of the genitalia.
METHODS: 1543 records of Mohs micrographic surgery performed during a 6-year period were reviewed to identify cases of BCC arising on the genitalia. Tumor tissue was analyzed for HPV DNA by in situ hybridization.
RESULTS: Four patients with BCC of the genitalia were treated with Mohs micrographic surgery. The malignancies were located on the scrotum, perineum, and perianal areas in the three male patients and on the vulva in the female patient. The mean age was 67 years. None of the patients had prior history of skin cancers. Histologic evaluation of the tumors revealed two nodular subtypes, one superficial subtype, and one with follicular differentiation. In situ hybridization failed to reveal DNA of HPV types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52.
CONCLUSION: In this small series, genital BCC occurred in an older age group with no identifiable predisposing risk factors and did not show evidence of HPV infection.
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78.) Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers.
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J Invest Dermatol 1998 Jul;111(1):123-7
Harwood CA, Spink PJ, Surentheran T, Leigh IM, Hawke JL, Proby CM, Breuer J, McGregor JM Department of Academic Dermatology, Royal Hospitals NHS Trust, London, UK.
Psoralen and UVA (PUVA) photochemotherapy is associated with a dose-dependent increased risk of nonmelanoma skin cancer in patients treated for psoriasis. Like ultraviolet B radiation, PUVA is both mutagenic and immunosuppressive and may thus act as a complete carcinogen; however, the reversed squamous to basal cell carcinoma ratio (SCC:BCC) in PUVA-treated patients, also seen in immunosuppressed renal transplant recipients, suggests a possible cofactor role for human papillomavirus (HPV) infection. In this study we examine a large series of benign and malignant cutaneous lesions for the presence of HPV DNA from patients treated with high dose (> or =500 J per cm2) ultraviolet A.
A panel of degenerate primers based on the L1 (major capsid protein) open reading frame was employed, designed to detect mucosal, cutaneous, and epidermodysplasia verruciformis HPV types with high sensitivity and specificity. HPV DNA was detected in 15 of 20 (75%) non-melanoma skin cancer, seven of 17 (41.2%) dysplastic PUVA keratoses, four of five (80%) skin warts, and four of 12 (33%) PUVA-exposed normal skin samples. The majority of HPV positive lesions contained epidermodysplasia verruciformis-related HPV including HPV-5, -20, -21, -23, -24, and -38. Possible novel epidermodysplasia verruciformis types were identified in further lesions.
Mixed infection with epidermodysplasia verruciformis, cutaneous, and/or mucosal types was present in six of 30 (20%) of all HPV positive lesions, including in normal skin, warts, dysplastic PUVA keratoses, and squamous cell carcinomas. The prevalence and type of HPV infection in cutaneous lesions from PUVA-treated patients is similar to that previously reported in renal transplant-associated skin lesions, and suggests that the role of HPV in PUVA-associated carcinogenesis merits further study.
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79.)Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses.
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J Invest Dermatol 1990 Nov;95(5):537-42
Kawashima M, Favre M, Obalek S, Jablonska S, Orth G Unite des Papillomavirus, Institut Pasteur, Paris, France.
To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population.
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80.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
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Arch Dermatol 1988 Jun;124(6):930-4
Obalek S, Favre M, Jablonska S, Szymanczyk J, Orth G Department of Dermatology, Warsaw School of Medicine, Poland.
Human papillomavirus-2 genomes were detected by molecular hybridization in two cases of basal cell carcinomas that developed in immunosuppressed individuals. This form of human papillomavirus is usually responsible for common warts in the general population. Although it does not appear to have oncogenic potential, it may be, in some cases, associated with cutaneousmalignancy.
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1.) Basal Cell Carcinoma in Children Report of 3 Cases
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Arch Dermatol. 2000;136:370-372
Benjamin W. LeSueur, BS; Nancy G. Silvis, MD; Ronald C. Hansen, MD
Background The peak incidence of basal cell carcinoma occurs in the seventh decade of life and is rare in children. When found in the pediatric age group, basal cell carcinoma is usually associated with a genetic defect, such as basal cell nevus syndrome, xeroderma pigmentosum, or nevus sebaceus. In areas of intense UV radiation exposure, such as the
southwestern United States, children may be at increased risk of developing this malignancy de novo.
Observations Three children (2 boys, aged 8 and 16 years, and an 11-year-old girl) from Tucson, Ariz, with isolated basal cell carcinoma unassociated with any other disease or syndrome are described.
Conclusions Basal cell carcinoma in children is probably the result of a combination of UV radiation exposure and genetic background. Early recognition in children can prevent extensive tissue destruction and excess scarring after excision. A higher index of suspicion for basal cell carcinoma may also aid in prompt diagnosis of a possible genetic disorder, such as basal cell nevus syndrome.
BASAL CELL carcinoma (BCC) in children is rare. Cases of BCC in the pediatric population have been reported in association with basal cell nevus syndrome,1 xeroderma pigmentosum,2 and nevus sebaceus3 and after high-dose radiotherapy.4 Isolated cases of BCC unrelated to one of these
causes are seldom reported in pediatric patients. Consequently, clinicians often have a low index of suspicion, leading to delay in diagnosis. We report 3 cases of de novo BCC in children who presented to the dermatology clinic at the University of Arizona Medical Center, Tucson. These children
had no known genetic syndromes and had not undergone radiotherapy.
COMMENT
=========
Non melanoma skin cancers are the most common malignant neoplasms in the United States, representing one third of all cancers diagnosed every year.5, 6 Basal cell carcinoma represents 75% of nonmelanoma skin cancers and has an estimated annual incidence of more than 700,000 cases nationally.7, 8 The US average annual incidence of BCC in whites is currently 191 per 100,000 and is increasing at a rate of 3% to 7% per year.7, 9
Ultraviolet radiation exposure is partly responsible for both BCC and squamous cell carcinoma, as evidenced by their increased prevalence after chronic exposure to sunlight and the preponderance of these lesions on sun-damaged skin. Although squamous cell carcinoma is associated with cumulative sun exposure, BCC in younger patients does not show this association.10, 11 D'Errico et al10 report that BCC arising before the age of 40 years corresponds with childhood or recreational sun exposure but does not correlate directly with cumulative sun damage. Thus, in areas of the world where the UV radiation is most intense, such as the Sunbelt in
the United States, childhood sun exposure is at a maximum and younger patients are at a higher risk of developing BCC.
Other factors besides sunlight are reported to influence the development of BCC. Gailani et al11 note a strong association between BCC and the inactivation of a gene at chromosome 9q22, which is thought to be a tumor suppressor. Inactivation of this gene was found in tumor tissue in 68% of BCCs examined and did not correlate directly with sun exposure or age. The cause of this mutation is unknown, but possible factors may include ionizing radiation, arsenicals, and polyaromatic hydrocarbons. Basal cell nevus syndrome and xeroderma pigmentosum represent inherited genetic mutations that predispose those affected to BCC. Patients with basal cell nevus syndrome are found to have a germline mutation on chromosome 9.12
The peak incidence of BCC occurs in the seventh decade of life.13 In the pediatric age group, BCC usually occurs in the setting of a known genetic defect (Table 1). Although uncommon, isolated BCC in children without these conditions has been reported.14-29 Price et al14 described a 17-year-old
boy with a solitary BCC of the nose. The patient had a history of sunburns 1 or 2 times per year since the age of 9 years. His mother had a BCC removed at the age of 44 years. Histologically, the tumor was described as superficial BCC. Scobie and Preston17 described a 4-year-old boy with a BCC of the scalp. The patient presented with a small "cyst" on the occipital
region of the scalp and a family history of skin cancer. The lesion, described histologically as well defined, recurred 8 months after excision. Excision was repeated without recurrence of tumor, based on follow-up 1 year later.17 A 12-year-old boy living in Arizona was described by Comstock et al18 with a BCC on the nose. The lesion had been present since his
nose was scratched by a cat 1 year earlier. The youngest patient with BCC, a 27-month-old infant, was described by Keramidas and Anagnostou.21 In this case, the lesion grew rapidly and ulcerated after a 4-month delay in diagnosis.
It is debatable whether BCC is more aggressive in children. Leffell et al30 defined aggressive-growth BCC as sclerosing, morpheaform, infiltrative, or invasive into nerves. Their retrospective review showed an increased occurrence of aggressive-growth BCC in patients younger than 35 years old compared with older patients. In contrast, Betti et al13 and Dinehart et al16 found no increase in the frequency of the morpheaform pattern in younger patients. All 3 of our patients had histologically less aggressive forms of BCC.
As total incidence rates of BCC continue to rise, childhood cases may become more common. This increase in pediatric BCC may be especially true in areas of high-level UV radiation exposure. The percentage of sunny days during the year, higher altitude, and location closer to the equator may
place children in these areas at increased risk. Early recognition can prevent extensive tissue destruction and scarring after excision and aid in prompt diagnosis of a possible genetic syndrome. We recommend that clinicians have a higher index of suspicion for BCC when evaluating questionable lesions in children.
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1. Gorlin RJ, Goltz RW. Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib.
N Engl J Med. 1960;262:908-912. 2.
Leibowitz E, Janniger CK, Schwartz RA, Lambert WC.
Xeroderma pigmentosum. Cutis. 1997;60:75-77, 81-84.
3. Goldstein GD, Whitaker DC, Argenyi ZB, Bardach J. Basal cell carcinoma arising in a sebaceous nevus during childhood.
J Am Acad Dermatol.1988;18:429-430.
4. Garcia-Silva J, Velasco-Benito JA, Pena-Penabad C, Armijo M. Basal cell carcinoma in a girl after cobalt irradiation to the cranium for acute lymphoblastic leukemia: case report and literature review. Pediatr Dermatol.1996;13:54-57.
5. Silverberg E, Lubera JA.
Cancer statistics, 1989. CA Cancer J Clin.1989;39:3-20.
6. Boring CC, Squires TS, Tong T Cancer statistics, 1991. CA Cancer J Clin.1991;41:19-36.
7. Silverberg E, Boring CC, Squires TS. Cancer statistics, 1990. CA Cancer J Clin.1990;40:9-26.
8. Parker SL, Tang T, Bolden S, Wingo PA. Cancer statistics, 1997.
CA Cancer J Clin.1997;47:5-27.
9. Green A. Changing patterns in incidence of nonmelanoma skin cancer. Epithelial Cell Biol.1992;1:47-51.
10. D'Errico M, Calcagnile AS, Corona R, et al. p53 mutations and chromosome instability in basal cell carcinomas
developed at an early or late age. Cancer Res.1997;57:747-752.
11. Gailani MR, Leffell DJ, Zeigler A, Gross EG, Brash DE, Bale AE. Relationship between sunlight exposure and a key genetic alteration in basal cell carcinoma. J Natl Cancer Inst. 1996;88:349-354.
12. Gailani MR, Bale SJ, Leffel DJ, DiGiovanna JJ, Peck GL, Poliak S. Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9. Cell. 1992;69:111-117. MEDLINE
13. Betti R, Inselvini E, Carducci M, Crosti C. Age and site prevalence of histologic subtypes of basal cell carcinomas.
Int J Dermatol. 1995;34:174-176.
14. Price MA, Goldberg LH, Levy ML. Juvenile basal cell carcinoma.
Pediatr Dermatol.1994;11:176-177.
15. Cox NH. Basal cell carcinoma in young adults. Br J Dermatol.1992;127:26-29.
16. Dinehart SM, Dodge R, Stanley WE, Franks HH, Pollack SV. Basal cell carcinoma treated with Mohs surgery: a comparison of 54
younger patients with 1050 older patients. J Dermatol Surg Oncol.1992;18:560-566.
17. Scobie WG, Preston J.
Basal cell carcinoma in children. J R Coll Surg Edinb.1992;37:46-47.
18. Comstock J, Hansen RC, Korc A. Basal cell carcinoma in a 12-year-old boy. Pediatrics.1990;86:460-462.
19. Cullen KW, Bleach NR, Green DM. Juvenile basal cell carcinoma.
Br J Clin Pract.1989;43:419-420.
20. Fliss DM, Hauben DJ, Ben-Meir P, Sion-Vardy N. Solitary basal cell carcinoma in a child. Ann Plast Surg.1989;22:43-46.
21. Keramidas DC, Anagnostou D. Basal cell carcinoma of the lower lid in a 27-month-old child. Z Kinderchir.1987;42:250-251.
22. Rahbari H, Mehregan AH.
Basal cell epithelioma (carcinoma) in children and teenagers. Cancer. 1982;49:350-353.
23. Henriksson C, Eldh J, Hersle K, Suurkula M. Basal cell carcinoma in children: case report. Scand J Plast Reconstr Surg.1981;15:157-158.
24. Hernandez-Perez E.
Basal cell carcinoma in children. Dermatologica.1975;150:311-315.
25. Milstone EB, Helwig EB.
Basal cell carcinoma in children. Arch Dermatol.1973;108:523-527.
26. Coskey RJ, Chow C.
Basal cell epitheliomas in children and young adolescents. Cutis.1973;12:224-226.
27. Botvinick I, Mehregan AH, Weissman F. Morphea-like basal cell epithelioma in a child. Arch Dermatol.1967;95:67-68.
28. Murray JE, Cannon B.
Basal-cell cancer in children and young adults.
N Engl J Med.1960;262:440-443.
29. Sewell RL. Basal cell carcinoma in youth. Arch Surg. 1941;42:909-912.
30. Leffel DJ, Headington JT, Wong DS, Swanson NA. Aggressive-growth basal cell carcinoma in young adults. Arch Dermatol.1991;127:1663-1667.
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2.) Papillomaviruses in non-melanoma skin cancer: epidemiological aspects.
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Semin Cancer Biol 1999 Dec;9(6):397-403
Kiviat NB
Department of Pathology, University of Washington, Seattle, WA, 98103,
USA
[Record supplied by publisher]
Worldwide, non-melanoma skin cancers (NMSCs), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are the most commonly diagnosed cancers among Caucasians. It is well established that ultraviolet radiation (UVR) plays a central role in the development of these cancers, and more recently, a role for specific genetic mutations in the pathogenesis of BCC has been identified. The possibility that certain types of HPV, either alone or in conjunction with UVR, may play a role in the pathogenesis of these cancers is suggested by several lines of evidence reviewed below.*9 @2depidemiology / non-melanoma skin cancer / papillomavirus Copyright 2000 Academic Press.
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3.) Reconstruction of the scalp and cranium using multiple free-tissue transfers following recurrent basal cell carcinoma.
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J Reconstr Microsurg 2000 Feb;16(2):89-93
Anderson PJ, Ragbir M, Berry RB, McLean NR
Department of Plastic and Reconstructive Surgery, Shotley Bridge General
Hospital, Durham, UK.
It is well-recognised that recurrent disease can occur following surgery
for malignancy in the head and neck region. This is particularly true of
basal cell carcinoma in which recurrences may occur over many years and despite the use of different treatment modalities. Reconstruction of large defects may become increasingly difficult and can be optimally managed by free tissue transfer. The authors report a case of basal cell carcinoma that has required treatment for over 20 years, unique in that on five different occasions, free flaps have been used for reconstruction.
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4.) Prognostic value of apoptotic index in cutaneous basal cell carcinomas of head and neck.
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Oral Oncol 1999 Nov 1;35(6):541-547
Staibano S, Lo Muzio L, Mezza E, Argenziano G, Tornillo L, Pannone G, De
Rosa G
Department of Biomorphological and Functional Sciences, Pathology
Section,
Faculty of Medicine and Surgery, University "Federico II", Naples, Italy
Basal cell carcinoma (BCC) is the most common type of human cancer, often locally invasive, and following a benign clinical course. However, a proportion of BCCs do recur after treatment, causing extensive local tissue destruction, seldom metastasizing. Morphological methods to unequivocally distinguish the aggressive forms of these tumors (BCC2) from the ordinary ones (BCC1) have so far been lacking. Apoptosis, or programmed cell death, is thought to be important for the death of tumor cells in various stages of carcinogenesis. We analyzed the extent of apoptosis in BCCs of head and neck in a morphological, morphometric, and electron-microscopic study, to estabilish on a retrospective basis, the relative frequency of recurrence of tumors showing different apoptotic rates. We found that BCC1 showed lower apoptotic index (AI) than BCC2 [BCC1: AI from 2.03 to 10.45% (mean
value: 5.98%) BCC2: AI from 21.91 up to 43.82% (mean value: 39.82%)]. The morphometric analysis of both BCC1 and BCC2 revealed significant differences between the values concerning nuclear area, length, perimeter, and roundness of the apoptotic cells with respect to the 'viable' neoplastic cells. Electron-microscopy confirmed that the features of morphological apoptotic cells were characteristic of programmed cell death. We hypothesized that low apoptotic rates in BCC1 could be indicative of a good prognosis. In fact, this corresponded to an 'expansive' but not still invasive neoplastic state. In this phase, however, the tumor cells may constitute the target for genetic changes triggered by enviromental physical or chemical mutagenic agents, such as UV rays. BCC2, then, could be the result of newly selected mutated neoplastic cellular clones, with
more aggressive biological behavior. The high apoptotic level found in BCC2 could thus be used as an indirect alarm signal from pathologists. This hypothesis seems to be supported by most of the current data in the literature and by the clinical outcome of BCC2 of our series. In our opinion, routine evaluation of apoptosis in BCCs could be proposed to facilitate their sub-classification, contributing toward the evaluation of the prospective outcome of the individual patients.
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5.) Low levels of urokinase plasminogen activator components in basal cell carcinoma of the skin.
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Int J Cancer 2000 Feb;85(4):457-459
Maguire T, Chin D, Soutar D, Duffy MJ
Department of Surgery, St. Vincent's Hospital, Dublin, Ireland.
Basal cell carcinoma of the skin (BCC) is the most common cancer worldwide. Unlike most other human malignancies, BCCs rarely metastasise. In this investigation, we show that the serine protease urokinase plasminogen activator (u-PA), which is causally involved in metastasis, is expressed at lower levels in BCCs compared to other skin cancers, such as squamous-cell carcinomas (SCCs) or malignant melanomas. Similarly, the u-PA receptor as well as the inhibitor PAI-1 were present at lower levels in BCCs relative to both SCCs and melanomas. In contrast to u-PA, tissue-plasminogen activator, which is not thought to be involved in metastasis, was present at similar levels in the different types of skin lesion investigated. We
conclude that the failure of BCCs to metastasise may at least be partially related to low expression of components of the u-PA system. Copyright 2000 Wiley-Liss, Inc.
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6.) Folliculotropic T cells in regressive basal cell carcinoma of skin.
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Am J Dermatopathol 2000 Feb;22(1):30-3
Lespi PJ, Gregorini SD
Department of Pathology, HIGA Dr Jose Penna, Bahia Blanca, Buenos Aires,
Argentina.
The histologic features of regression may be found in some basal cell carcinomas (BCCs), and it is known that T-cell infiltrates have a significant role in host defense against this tumor. We examined 945 hair follicles (HFs) adjacent to 150 regressing BCCs of skin for the presence of inflammatory infiltrates and compared the results against 315 HFs in 50 samples of normal skin. Focal T-cell infiltrates localized mainly to the
upper portion of the HFs were found in 14.5% of the follicles adjacent to regressing BCCs. A statistically significant increase of inflammation in
HFs was observed in BCCs with active regression compared with BCCs with inactive and mixed regression (P < 0.05). An increase in the number of HFs involved by T lymphocytes was also found in regressing BCCs compared to normal skin ( P < 0.00005). These data suggest that the damage to the follicles is concordant with active regression of BCCs. We speculate that the immune-mediated regression of BCCs is not only specifically directed to the cells of the tumor but may also induce activated lymphocytes with cytotoxic capability to cross react with the follicular epithelium.
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7.) Repeated 5-aminolevulinic acid-based photodynamic therapy following electro-curettage for pigmented basal cell carcinoma.
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J Dermatol 2000 Jan;27(1):10-5
Itoh Y, Henta T, Ninomiya Y, Tajima S, Ishibashi A
Department of Dermatology, National Defense Medical College, Tokorozawa,
Japan.
5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) in the
standard
manner is ineffective for pigmented basal cell carcinoma (pBCC), because
melanin absorbs the photoactivating light interred for protoporphyrin
IX. The objective of this study was to assess the therapeutic outcome of pBCCs with repeated ALA-PDT following removal of pigmentation with electro-curettage. After electro-curettage, 16 pBCCs were treated with a
combination of topical application of 20% ALA in O/W emulsion and topical instillation of 10% ALA solution, followed by photoactivating light. ALA-PDT was performed more than three times. Fourteen of 16 pBCCs showed
CR. Two pBCCs showing PR or NR were excised. Repeated ALA-PDT following electro-curettage was effective for pBCC.
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8.) Sporadic Bazex-Dupre-Christol-like Syndrome: Early Onset Basal Cell Carcinoma, Hypohidrosis, Hypotrichosis, and Prominent Milia.
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Dermatol Surg 2000 Feb;26(2):152-154
Glaessl A, Hohenlautner U, Landthaler M, Vogt T
Department of Dermatology, University of Regensburg, Regensburg,
Germany.
BACKGROUND: We present the case of a 32-year-old woman with a large recurrent multifocal basal cell carcinoma on the scalp. Conspicuous accompanying symptoms were multiple periorbital milia, hypotrichosis of the body and the scalp, and hypohidrosis. The sparse hair of the scalp showed further abnormalities such as pili torti, as well as flattened, irregularly curly hairs. OBJECTIVE: In 1964, Bazex et al. described a syndrome characterized by congenital hypotrichosis, follicular atrophoderma, and basocellular neoplasms that included basal cell nevi and early onset basal cell carcinomas. The Bazex-Dupre-Christol syndrome is a rare X-linked dominant disease. A sporadic occurrence with the typical constellation of these symptoms has not yet been reported. The lack of a positive family history and no signs of follicular atrophoderma argues for a sporadic occurrence of a Bazex-Dupre-Christol-like syndrome. The case reported shares several features with the classic Bazex-Dupre-Christol syndrome. CONCLUSION: Our report documents the necessity to look for early development of basal cell carcinomas in patients who show signs of the epidermal malformations described.
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9.) Reporting basal cell carcinoma: a survey of the attitudes of histopathologists.
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J Clin Pathol 1999 Nov;52(11):867-9
Milroy CJ, Richman PI, Wilson GD, Sanders R
Restoration of Function and Appearance Trust, Mount Vernon Hospital,
Northwood, Middlesex, UK. milroy@graylab.ac.uk
AIMS: To investigate the histopathological reporting of basal cell carcinoma. METHODS: Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). RESULTS: 24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of different classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were differences in methods of processing and reporting biopsies. CONCLUSIONS: There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for
uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer.
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10.) Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an italian case-control study.
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J Am Acad Dermatol 2000 Mar;42(3):446-52
Naldi L, DiLandro A, D'Avanzo B, Parazzini F
[Medline record in process]
BACKGROUND: Despite its frequency, there is a paucity of data on risk factors for basal cell carcinoma. OBJECTIVE: We assessed potential risk factors for basal cell carcinoma in a population from southern Europe. METHODS: This multicenter case-control study involved 528 newly diagnosed cases and 512 controls. RESULTS: In the multivariate analysis, red hair,
lighter colored eyes, high nevus counts on the upper limbs, and the presence of solar lentigines and actinic keratoses were all associated with basal cell carcinoma. The risk of the tumor increased in subjects who reported burning easily and experiencing sunburn episodes before 15 years of age. An association was documented with indices of recreational sun exposure but no clear evidence of exposure-effect relationship was found. No relation was found with occupational sun exposure. Finally, basal cell carcinoma appeared to be significantly associated with a family history of skin tumors, a personal history of tumors other than those on skin, and radiotherapy. CONCLUSION: Genetic and environmental factors appear to be
involved in the onset of basal cell carcinoma.
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11.) Collagenolytic and gelatinolytic matrix metalloproteinases and their inhibitors in basal cell carcinoma of skin: comparison with normal skin.
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Br J Cancer 2000 Feb;82(3):657-65
Varani J, Hattori Y, Chi Y, Schmidt T, Perone P, Zeigler ME, Fader DJ,
Johnson TM
Department of Pathology, The University of Michigan Medical School, Ann
Arbor 48109, USA.
Tissue from 54 histologically-identified basal cell carcinomas of the skin was obtained at surgery and assayed using a combination of functional and immunochemical procedures for matrix metalloproteinases (MMPs) with collagenolytic activity and for MMPs with gelatinolytic activity. Collagenolytic enzymes included MMP-1 (interstitial collagenase), MMP-8 (neutrophil collagenase) and MMP-13 (collagenase-3). Gelatinolytic enzymes included MMP-2 (72-kDa gelatinase A/type IV collagenase) and MMP-9 (92-kDa gelatinase B/type IV collagenase). Inhibitors of MMP activity including tissue inhibitor of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) were
also assessed. All three collagenases and both gelatinases were detected
immunochemically. MMP-1 appeared to be responsible for most of the functional collagenolytic activity while gelatinolytic activity reflected both MMP-2 and MMP-9. MMP inhibitor activity was also present, and appeared, based on immunochemical procedures, to reflect the presence of
TIMP-1 but not TIMP-2. As a group, tumours identified as having aggressive-growth histologic patterns were not distinguishable from basal cell carcinomas with less aggressive-growth histologic patterns. In normal skin, the same MMPs were detected by immunochemical means. However, only
low to undetectable levels of collagenolytic and gelatinolytic activities were present. In contrast, MMP inhibitor activity was comparable to that
seen in tumour tissue. In previous studies we have shown that exposure of normal skin to epidermal growth factor in organ culture induces MMP up-regulation and activation. This treatment concomitantly induces stromal invasion by the epithelium (Varani et al (1995) Am J Pathol 146: 210-217; Zeigler et al (1996b) Invasion Metastasis 16: 11-18). Taken together with these previous data, the present findings allow us to conclude that the same profile of MMP/MMP inhibitors that is associated with stromal invasion in the organ culture model is expressed endogenously in basal cell carcinomas of skin.
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12.) A Cancer-Registry-Assisted Evaluation of the Accuracy of Digital Epiluminescence Microscopy Associated with Clinical Examination of Pigmented Skin Lesions.
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Dermatology 2000;200(1):11-16
Stanganelli I, Serafini M, Bucch L
Skin Cancer Clinic, Center for Cancer Prevention, Department of
Prevention,
Ravenna Health Care District, Ravenna, Italy.
BACKGROUND: The accuracy of digital epiluminescence microscopy (D-ELM) as an adjunct to clinical examination for the diagnosis of pigmented skin lesions (PSLs) has seldom been evaluated. OBJECTIVE: To compare the accuracy of the combined clinical/D-ELM (C/D-ELM) examination with that of the clinical examination alone. METHODS: A total of 3,372 PSLs from 1,556 consecutive patients referred to a skin cancer clinic underwent clinical
examination and a combined C/D-ELM examination. The reference diagnosis was established using the histology report of known surgical excisions plus a cancer-registry-based follow-up (duration 18 months) of benign C/D-ELM diagnoses. The two diagnostic approaches were compared for sensitivity, predictive value and false-positive rate. RESULTS: The series included 55 melanomas and 43 basal cell carcinomas. About 50% of malignant misdiagnosed cases were identified solely through the cancer registry. The C/D-ELM diagnosis showed a greater sensitivity for melanoma <0.76 mm thick (83 vs. 46% for clinical examination alone; ratio, 1.82) and basal cell carcinoma (79 vs. 49%; ratio, 1.62), a greater predictive value for melanoma (81 vs. 53%; ratio, 1.53) and a reduced total false-positive rate (0.3 vs. 0.9%;
ratio, 0.31). CONCLUSION: D-ELM showed a potential to improve the clinical diagnosis of PSL. Copyright (R) 2000 S.Karger AG, Basel
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13.) Expression of p53 in arsenic-related and sporadic basal cell carcinoma.
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Arch Dermatol 2000 Feb;136(2):195-8
Boonchai W, Walsh M, Cummings M, Chenevix-Trench G
The Queensland Institute of Medical Research, University of Queensland,
Brisbane, Australia.
BACKGROUND: The TP53 gene has been shown to have an important role in the genesis of sporadic, presumably mainly sunlight-related, basal cell carcinoma (BCC). However, its role in arsenic-related BCCs is not clear,
although the trivalent form of arsenic has been long recognized as a cause of BCC. Arsenic treatment has been shown to cause hypermethylation of the TP53 gene in lung carcinoma cell lines, but it is not known if this occurs in vivo in arsenic-related BCCs. OBJECTIVE: To compare the immunohistochemical expression of the p53 protein in arsenic-related and
sporadic BCCs to determine if the expression pattern is consistent with gene silencing. SETTING: A research institute and hospital in Australia.
CASES: One hundred seventeen white patients with 121 sporadic BCCs and 21 white patients with 92 arsenic-related BCCs. MAIN OUTCOME MEASURES: The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi2 test. RESULTS: Arsenic-related BCCs express p53 less often and at a lower intensity than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpression of p53 than those from less-exposed areas (P = .004; 2-tailed test). T
he more aggressive subtypes of BCC show a higher level of expression of p53 than the less aggressive forms (P = .04; 2-tailed chi2 test). CONCLUSIONS: These results are consistent with the hypothesis that the TP53 gene is down-regulated by methylation in arsenic-related BCC, particularly those from less-exposed sites. However, an alternative possibility is that mutations in TP53 that stabilize the protein are less common in arsenic-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.
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14.) Decision support software to help primary care physicians triage skin cancer: a pilot study.
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Arch Dermatol 2000 Feb;136(2):187-92
Gerbert B, Bronstone A, Maurer T, Hofmann R, Berger T
Division of Behavioral Sciences, School of Dentistry, University of California, San Francisco 94111, USA. gerbert@itsa.ucsf.edu
OBJECTIVE: To determine whether decision support software can help primary care physicians proficiently triage lesions suggestive of basal cell and squamous cell carcinoma. DESIGN/MEASURES: Physicians selected triage options for 15 digitized images of skin lesions, with and without use of the decision support software.
PARTICIPANTS/SETTINGS:
Twenty primary care physicians practicing in a health maintenance organization or a city health clinic.
INTERVENTION:
Decision support software designed to help physicians arrive at a triage recommendation consisted of a clinical information form, a decision tree, and support features (teaching points, example images, and diagrams).
RESULTS: Without using the decision support software, physicians chose the wrong triage decision 36.7% of the time; using the decision support software, they chose the wrong response only 13.3% of the time. Not using the decision support software, they failed to correctly perform a biopsy on or refer patients with cancerous lesions 22.1% of the time; using the software, they failed to correctly perform a biopsy on or refer patients with cancerous lesions only 3.6% of the time. Physicians scored an average of 3 points (of a possible 15 points) higher when they used the software (signed rank, 101.0; P<.001). They scored an average of 1 point
higher on the 7 cancerous lesions when they used the software (signed rank, 65.5; P<.001).
CONCLUSIONS:
Use of decision support software could improve primary care physicians' triage decisions for lesions suggestive of nonmelanoma skin cancer, and potentially reduce morbidity and health care costs. We are designing a larger study to evaluate the accuracy and utility of the software with patients seen in clinical practice.
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15.) A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study.
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Arch Dermatol 2000 Feb;136(2):179-84
Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard
Medical School, Boston, Mass, USA.
CONTEXT: Although basic research provides plausible mechanisms for benefits of beta carotene supplementation on nonmelanoma skin cancer (NMSC) primarily consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), observational studies are inconsistent. Randomized trial data are limited to 1 trial of secondary prevention that showed no effect of beta carotene on the incidence of NMSC after 5 years.
OBJECTIVE: To test whether supplementation with beta carotene reduces the risk for development of a first NMSC, including BCC and SCC.
DESIGN: Randomized, double-blind, placebo-controlled trial with 12 years of beta carotene supplementation and follow-up. SETTING: Physicians' Health Study in the United States.
PARTICIPANTS: Apparently healthy male physicians aged 40 to 84 years in 1982 (N = 22 071). INTERVENTION: Beta carotene, 50 mg, on alternate days. MAIN OUTCOME MEASURE: Relative risk (RR) and 95% confidence interval (CI) for a first NMSC, BCC, and SCC. RESULTS: After adjusting for age and randomized aspirin assignment, there was no effect of beta carotene on the incidence of a first NMSC (RR, 0.98; 95% CI, 0.92-1.05), BCC (RR, 0.99; 95% CI, 0.92-1.06), or SCC (RR, 0.97; 95% CI, 0.84-1.13). There was also no significant evidence of beneficial or harmful effects of beta carotene on NMSC by smoking status (current, past, or never).
CONCLUSION: This large-scale, randomized, primary prevention trial among apparently healthy well-nourished men indicates that an average of 12 years of supplementation with beta carotene does not affect the development of a first NMSC, including BCC and SCC.
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16.) Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate.
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Cancer Res 2000 Feb 1;60(3):525-9
Henderson BW, Busch TM, Vaughan LA, Frawley NP, Babich D, Sosa TA, Zollo
JD, Dee AS, Cooper MT, Bellnier DA, Greco WR, Oseroff AR
Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New
York 14263, USA.
At high fluence rates in animal models, photodynamic therapy (PDT) can photochemically deplete ambient tumor oxygen through the generation of singlet oxygen, causing acute hypoxia and limiting treatment effectiveness. We report that standard clinical treatment conditions (1 mg/kg Photofrin, light at 630 nm and 150 mW/cm2), which are highly effective for treating
human basal cell carcinomas, significantly diminished tumor oxygen levels during initial light delivery in a majority of carcinomas. Oxygen depletion could be found during at least 40% of the total light dose, but tumors appeared well oxygenated toward the end of treatment. In contrast, initial light delivery at a lower fluence rate of 30 mW/cm2 increased tumor oxygenation in a majority of carcinomas. Laser treatment caused an intensity- and treatment time-dependent increase in tumor temperature. The data suggest that high fluence rate treatment, although effective, may be inefficient.
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17.) Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells.
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Jpn J Cancer Res 1999 Dec;90(12):1351-7
Fujii K, Miyashita T, Takanashi J, Sugita K, Kohno Y, Nishie H, Yasumoto
S,
Furue M, Yamada M
Department of Genetics, National Children's Medical Research Center,
Tokyo.
The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that gamma-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell
lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after gamma-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after gamma-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after gamma-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.
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18.) Expression of desmoglein I and plakoglobin in skin carcinomas.
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J Cutan Pathol 2000 Jan;27(1):24-9
Tada H, Hatoko M, Tanaka A, Kuwahara M, Muramatsu T
Division of Plastic Surgery, Nara Medical University, Japan.
Reduction or absence of cell-cell adhesion molecules has been reported in various carinomas and the abnormal expression of these molecules contributes to the invasive and metastatic behavior of malignant tumor cells. In epidermal keratinocytes, the main cell-cell adhesion systems are adherens junctions and desmosomes. Previous studies have shown that, in skin carcinomas, the decreased expression of E-cadherin, major constitutional glycoprotein of adherens junctions, is associated with the invasive and metastatic ability of the tumor cells. In the present study, we examined the expression of desmoglein I and plakoglobin, the constitutional components of desmosomes, in various skin carcinomas such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), extramammary Paget's disease and Bowen's disease by an immunofluorescence method. In normal human skin, desmoglein I and plakoglobin were strongly expressed in the intercellular space of the epidermis except for the basal cell layer. In BCC and SCC, the expression of desmoglein I and plakoglobin was markedly reduced or absent in tumor cells.
In carcinoma in situ of Paget's disease, compared with the normal epidermal cells surrounding tumor cell nests, the expression of these molecules was reduced in tumor cells. In Paget's disease with dermal infiltration of tumor cells, the expression of these molecules was almost absent throughout the epidermis. In Bowen's disease, the expression of desmoglein I was reduced in the dumping cells and dyskeratotic cells. These results suggest that the expression of desmosomal cadherin is reduced or absent in human skin carcinomas, and that reduction of these molecules may also contribute to the invasiveness and metastasis of skin carcinomas.
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19.) Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous basal and squamous cell carcinomas.
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Anticancer Res 1999 Jul-Aug;19(4B):2929-38
Dumas V, Kanitakis J, Charvat S, Euvrard S, Faure M, Claudy A
INSERM U346, Lyon, France.
BACKGROUND: Basement membrane (BM) antigens and matrix metalloproteinases (MMP) are involved in tumor invasion and metastasis. Basal (BCC) and squamous cell carcinomas (SCC) differ with respect to their biological behavior since the former are only locally aggressive whereas the latter
have a metastatic potential. MATERIALS AND METHODS:
We studied the immunohistochemical expression of several BM antigens and of MMP2 and MMP9, in 13 BCC, 13 SCC, and 8 in situ skin carcinomas. RESULTS: The expression of most BM antigens was reduced in the tumors in comparison with normal skin. Hemidesmosome- and lamina lucida-associated antigens (plectin, NUT2, alpha 6/CD49f and laminin-5) were more decreased in BCC, whereas collagens type VII and IV were more decreased in SCC as compared with BCC; in BCC and SCC both collagens tended to be decreased on the leading edge of invasive tumor masses. In situ carcinomas showed a slightly diminished expression of alpha 6/CD49f integrin, plectin and NUT2. The expression of both MMP2 and MMP9 was increased in SCC as compared with BCC.
CONCLUSION: Our findings further upheld the role of BM antigens and MMPs in the process of tumor aggressiveness. The reduced expression of collagen IV, combined with an increased expression of both MMP2 and MMP9 could account for the increased metastatic potential of SCC vs BCC through an increased invasion of the extracellular matrix and the vascular space.
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20.) Detoxifying enzyme genotypes and susceptibility to cutaneous malignancy.
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Br J Dermatol 2000 Jan;142(1):8-15
Lear JT, Smith AG, Strange RC, Fryer AA
Department of Dermatology, Clinic 6, Bristol Royal Infirmary, Bristol
BS2
8HW, U.K.; *Department of Dermatology, North Staffordshire NHS Trust, Stoke on Trent ST4 7PA, U.K.; Department of Dermatology, Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke on Trent ST4 7PA, U.K.
While ultraviolet (UV) exposure is thought to be a major risk factor for basal cell carcinoma (BCC) and squamous cell carcinoma, more recent research has focused on genetic factors predisposing to these cancers. UV constitutes an oxidative stress with generation of free radicals, leading to lipid and DNA damage and gene mutation. It could therefore be hypothesized that individual ability to deal with these products may be important in cutaneous carcinogenesis. It is clear from recent studies that polymorphisms in detoxifying enzyme genes are important in determining susceptibility to skin cancer.
The magnitude of effect in BCC is similar to that seen with many other previously described risk factors. However, uncertainties exist regarding the phenotypic consequences of some of these polymorphisms and relevant substrates. This review describes the influence of polymorphisms in detoxifying enzymes in determining susceptibility to skin cancer (in particular to BCC) and give a brief overview of the biochemistry of the detoxification process.
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21.) Tumors arising in nevus sebaceus: A study of 596 cases.
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J Am Acad Dermatol 2000 Feb;42(2 Pt 1):263-8
Cribier B, Scrivener Y, Grosshans E
Laboratoire d'Histopathologie Cutanee, Clinique Dermatologique des
Hopitaux
Universitaires de Strasbourg, France.
BACKGROUND: Prophylactic surgical excision of nevus sebaceus (NS) during childhood is often recommended because various neoplasms can occur on NS. The proportion of malignant tumors occurring on NS is highly variable among the published series, and there are controversies on the nature of these neoplasms because many of the previously described basal cell carcinomas could actually be trichoblastomas, which are benign follicular tumors.
OBJECTIVE: We retrospectively analyzed all cases of NS of our collection, excised during the period from 1932 through 1998, and recorded all associated epithelial and nonepithelial changes. We especially differentiated basal cell carcinomas from trichoblastomas by silhouette analysis and examination of the stroma. These findings were analyzed according to gender, age, and localization.
METHODS:
Microscopic analysis of NS by two examiners was performed independently of clinical data.
RESULTS:
A total of 596 cases were included from 290 females and 306 males, mean age 25.4 years (range, 1 month to 87 years); 232 were excised in children younger than 16 years. NSs were located on the scalp in 49.8% of cases. Basal cell carcinomas were found in 5 cases (0.8%, mean age 39.3 years) and benign tumors in 81 cases (13.6%, mean age 46.3 years). Syringocystadenoma papilliferum (n = 30, 15 males, 15 females) and trichoblastoma (n = 28, 7 males, 21 females) were the most frequent benign tumors. NS with associated tumors were located on the scalp in 79% of cases. Only 4 benign tumors (1.7%) and 2 warts were observed in patients younger than 16 years. Various types of epithelial hyperplasia were noted that could not be considered neoplasms, as well as epidermal and apocrine cysts.
CONCLUSION:
The rate of malignant tumors arising on NS was very low and we did not observe such cases in children, who had associated benign tumors in only 1.7% of cases. Benign neoplasms were common and most of them occurred on the scalp; this was not a bias resulting from a longer duration before surgery. Trichoblastoma and not basal cell carcinoma was the most frequent follicular tumor associated with NS and showed a striking female predominance. Most trichoblastomas had previously been misdiagnosed but could actually be easily recognized by typical histologic features. Because most tumors occurred in adults older than 40 years, our study suggests that prophylactic surgery in young children is of uncertain benefit. Clinical follow-up is probably sufficient, and even those cases with clinical changes often proved to be benign tumors or warts.
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22.) Liposome-mediated gene transfer into human basal cell carcinoma.
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Gene Ther 1999 Dec;6(12):1929-35
Hottiger MO, Dam TN, Nickoloff BJ, Johnson TM, Nabel GJ Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, Ann Arbor, MI, USA.
Direct intralesional injection of DNA encoding interferon-alpha2 (IFN-alpha2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%). Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-alpha2 using this method resulted in sustained production of IFN-alpha2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-alpha protein may therefore be applicable to the treatment of cutaneous BCC.
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23.) Proliferative Actinic Keratosis: Three Representative Cases.
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Dermatol Surg 2000 Jan;26(1):65-69
Goldberg LH, Chang JR, Baer SC, Schmidt JD
OBJECTIVE:
This article describes a new subtype of actinic keratosis that exhibits proliferative characteristics both histologically and clinically. We describe three representative cases occuring in the presence of infiltrative squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC).
METHODS: Histories of each lesion in the three cases discussed were obtained. The lesions were removed by Mohs micrographic surgery. Permanent sections, stained with hematoxylin and eosin, were examined and studied under light microscopy.
RESULTS: All three lesions had failed conventional treatment with liquid nitrogen and/or 5-fluorouracil (5-FU). Histologic examination of the lesions revealed sheets of dysplastic cells growing along the basal layer of the epidermis and migrating down hair follicles and sweat ducts. An associated infiltrative SCC and/or BCC was found in each case.
CONCLUSIONS: Proliferative actinic keratosis is resistant to standard therapies because of deep migration of abnormal cells along hair follicles and sweat ducts. It has a strong propensity to develop infiltrative SCC and may occur concomitantly with BCC.
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24.) Diet and basal cell carcinoma of the skin in a prospective cohort of men.
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Am J Clin Nutr 2000 Jan;71(1):135-41
van Dam RM, Huang Z, Giovannucci E, Rimm EB, Hunter DJ, Colditz GA, Stampfer MJ, Willett WC Departments of Nutrition and Epidemiology, Harvard School of Public Health,
Boston, MA 02115, USA.
BACKGROUND: Low intake of fat and high intake of specific vitamins have been hypothesized to reduce risk of basal cell carcinoma of the skin (BCC).
OBJECTIVE:
Our objective was to examine intakes of fat, antioxidant nutrients, retinol, folate, and vitamin D in relation to risk of BCC. DESIGN: In 1986, diet was assessed by a validated food-frequency questionnaire in 43217 male participants of the Health Professionals Follow-up Study who were 40-75 y of age and free of cancer. During 8 y of follow-up, we ascertained 3190 newly diagnosed cases of BCC.
RESULTS:
Total fat consumption was associated with a lower risk of BCC [relative risk (RR): 0.81; 95% CI: 0.72, 0.90 for the highest compared with the lowest quintile of intake; P for trend < 0.001). Simultaneous modeling of specific fatty acids suggested that this inverse association was limited to monounsaturated fat (RR: 0.79; 95% CI: 0.65, 0.96; P for trend = 0. 02); saturated and polyunsaturated fat were not associated with BCC risk. Folate intake was associated with a slightly higher risk of BCC (RR: 1.19; 95% CI: 1.01, 1.40; P for trend = 0.11), whereas alpha-carotene was associated with a slightly lower risk (RR: 0.88; 95% CI: 0.79, 0.99; P for trend = 0.01). Intakes of long-chain n-3 fatty acids, retinol, vitamin C, vitamin D, or vitamin E were not materially related to BCC risk.
CONCLUSIONS:
These findings do not support the hypothesis that diets low in fat or high in specific vitamins lower risk of BCC.
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25.) Preliminary observations on the use of topical tazarotene to treat basal-cell carcinoma.
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N Engl J Med 1999 Dec 2;341(23):1767-8
Peris K, Fargnoli MC, Chimenti S
Publication Types:
Letter
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26.)HLA phenotypes and multiple basal cell carcinomas.
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SO - Dermatology 1994;189(3):222-4
AU - Rompel R; Petres J; Kaupert K; Mueller-Eckhardt G
PT - JOURNAL ARTICLE
AB - BACKGROUND: Previous investigators noted an association of multiple
basal cell carcinomas (BCC) with certain HLA antigens; however, these findings were contradictory, and the associations were only weak.
OBJECTIVE: The aim of the study was to objectify the previously found associations.
METHODS: Serologic HLA typing for class I and class II antigens was performed in 49 unrelated patients with 5 or more BCCs. RESULTS: HLA-DR4 showed decreased frequencies in the patient group as compared with healthy controls (n = 716). Cw7 was found to be increased in the total group of patients as well as in a subgroup with multiple BCCs of the face (n = 24), while a subgroup with BCCs mainly on the trunk (n = 25) revealed increased frequencies of HLA-A11, -B17, -B22 and -Cw3. However, none of these deviations appeared significant after correction of p values.
CONCLUSION: We conclude that, if at all, the HLA system plays only a minor role in the development of multiple BCCs.
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27.) Multiple non-melanoma skin cancer: evidence that different MHC genes are associated with different cancers.
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SO - Dermatology 1994;188(2):88-90
AU - Czarnecki D; Tait B; Nicholson I; Lewis A
PT - JOURNAL ARTICLE
AB - HLA DR frequencies of patients with multiple non-melanoma skin cancers were analysed. There were significant differences in the frequencies of HLA DR1, DR4 and DR7 between patients who only had basal cell carcinomas and patients who had both basal and squamous cell carcinomas. There were significant differences in the frequency of HLA DR53 between the two groups. This antigen is in linkage disequilibrium with HLA DR4 and DR7, and it is not possible to distinguish the primary susceptibility locus.
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28.) HLA DR4 is associated with the development of multiple basal cell carcinomas and malignant melanoma.
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SO - Dermatology 1993;187(1):16-8
AU - Czarnecki D; Nicholson I; Tait B; Nash C
PT - JOURNAL ARTICLE
AB -
An association between HLA DR4 and the development of multiple basal cell carcinomas (BCC) and malignant melanoma (MM) was detected in southern Australia. There were highly significant differences in HLA DR frequencies between patients with multiple BCCs and MM and matched patients with multiple BCCs only. These findings suggest that hereditary factors associated with the HLA system influence what types of multiple skin cancers people develop.
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29.) Multiple basal cell carcinoma in tropical Australia.
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SO - Int J Dermatol 1992 Sep;31(9):635-6
AU - Czarnecki D; Collins N; Chow P; Nicholson I; Tait B
PT - JOURNAL ARTICLE
AB - No association between HLA DR1 and the development of multiple basal cell carcinomas (BCC) was found among patients who had lived at least two-thirds of their lives in the tropics. The percentage of patients with multiple BCCs increased with age; this was different from what has been found in people living in the temperate zone of Australia.
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30.) HLA-DR1 is not a sign of poor prognosis for the development of multiple basal cell carcinomas.
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SO - J Am Acad Dermatol 1992 May;26(5 Pt 1):717-9
AU - Czarnecki D; Lewis A; Nicholson I; Tait B; Nash C
PT - JOURNAL ARTICLE
AB - BACKGROUND: HLA-DR1 is associated with the development of multiple basal cell carcinomas (BCC). However, the association is weak.
OBJECTIVE: The purpose of our study was to determine whether HLA-DR1 is a marker for susceptibility to the development of many BCCs during a lifetime.
METHODS: Persons with multiple BCCs were placed into two groups: those with less than 10 and those with 20 or more. In addition, the HLA-DR1 frequencies were analyzed. RESULTS: HLA-DR1 was associated with multiple BCCs in the
group with less than 10 BCCs but not with the other group. These patients were significantly younger on average than those with 20 or more BCCs.
CONCLUSION: HLA-DR1 is associated with the development of multiple BCCs at an early age but it is not associated with development of large numbers of BCCs. The amount of UV light a person receives appears to be more important.
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31.) Multiple basal cell carcinomas and HLA frequencies in southern Australia.
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SO - J Am Acad Dermatol 1991 Apr;24(4):559-61
AU - Czarnecki D; Lewis A; Nicholson I; Tait B
PT - JOURNAL ARTICLE
AB
- An association between HLA-DR1 and the development of multiple basal cell carcinomas was detected in southern Australia. A reduction in HLA-DR4 was found in patients with basal cell carcinoma compared with a local control group. The relative risk for HLA-DR1 was 2.1, which was lower than that for persons in farther countries from the equator.
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32.) Expression of human lymphocyte antigen (HLA)-DR on tumor cells in basal cell carcinoma.
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SO - J Am Acad Dermatol 1987 Apr;16(4):833-8
AU - Kohchiyama A; Oka D; Ueki H
PT - JOURNAL ARTICLE
AB - Immunohistologic studies of eight patients with basal cell carcinoma were undertaken using a series of monoclonal antibodies. In all of the patients, the majority of dermal infiltrates reacted with OKT3 and OKIa1
(HLA-DR), with a slight predominance of OKT4+ helper/inducer T cells (the mean OKT4/OKT8 ratio was 1.8). Both OKT4+ and OKT8+ cells were seen infiltrating the tumor masses. In addition, in five cases, human lymphocyte antigen (HLA)-DR was demonstrated on some tumor cells close to a vast number of HLA-DR+ infiltrates surrounding the carcinoma, but not on epidermal keratinocytes and tumor cells devoid of the HLA-DR+ infiltrates. A considerable number of OKT6+ dendritic cells were also observed surrounding the carcinoma. Staining with OKB7 and OKM1 revealed negligible reactive cells, and virtually none of the dermal infiltrates reacted with Leu-7 (HNK-1). These findings suggest that in addition to varied immunologically competent cells, expression of HLA-DR antigen on tumor cells may participate in a cellular immune reaction, a defense mechanism against tumor cell proliferation in basal cell carcinoma.
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33.) Human leukocyte antigen associations in basal cell carcinoma.
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SO - J Am Acad Dermatol 1985 Jun;12(6):997-1000
AU - Myskowski PL; Pollack MS; Schorr E; Dupont B; Safai B
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma is the most common form of skin cancer and is
one in which both host and environmental factors are thought to play a
role in its pathogenesis. For an investigation of the role of human leukocyte antigen (HLA)-associated variations in genetic susceptibility, thirty-one patients with multiple basal cell carcinomas were typed for HLA-A, B, C, and DR antigens. Patients were compared with both local and appropriate ethnic group controls. No statistically significant association with HLA-A, B, or C antigens was noted in any group. However, a significant increase in HLA-DR1 was noted in non-Irish, non-Ashkenazi patients. A tendency toward a decrease in HLA-DR3 was also noted among patients of Irish or Ashkenazi Jewish descent. The role of HLA-associated genetic factors in this form of skin cancer needs further investigation.
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34.) Translocation (4; 14) and concomitant inv(14) in a basal cell carcinoma.
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SO - Cancer Genet Cytogenet 1991 Oct 15;56(2):177-80
AU - Kawasaki RS; Caldeira LF; Andre FS; Gasques JA; Castilho WH;
Bozola
AR; Thome JA; Tajara EH
PT - JOURNAL ARTICLE
AB - Chromosome analysis of short-term cultures from a basal cell carcinoma was performed. The analyzed karyotypes showed a pseudodiploid clone characterized by a der(4)t(4; 14) (p14; p11) and a concomitant inversion of the same chromosome 4 involved in the t(4; 14) with the breakpoints at p14 and q25.
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35.) Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group [see comments]
============================================================
SO - J Natl Cancer Inst 1992 Mar 4;84(5):328-32
AU - Tangrea JA; Edwards BK; Taylor PR; Hartman AM; Peck GL; Salasche SJ;
Menon PA; Benson PM; Mellette JR; Guill MA; et al
PT - CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
AB - BACKGROUND:
High-dose isotretinoin has been reported to have a prophylactic effect on nonmelanoma skin cancer, although it is associated with significant toxicity. PURPOSE: To test the effectiveness of the long-term administration of low-dose isotretinoin in reducing the occurrence of basal cell carcinoma at a new site in patients with previously treated basal cell carcinomas and to measure the toxicity associated with this regimen, we conducted a clinical trial at eight cancer centers.
METHODS: Nine hundred and eighty-one patients with two or more previously confirmed basal cell carcinomas were randomly assigned to receive either 10 mg of isotretinoin or a placebo daily. Patients were followed for 36 months and monitored at 6-month intervals for skin cancer and toxic effects.
RESULTS: After 36 months of treatment, no statistically significant difference in either the cumulative percent of patients with an occurrence of basal cell carcinoma at a new site or the annual rate of basal cell carcinoma formation existed between patients receiving isotretinoin and those receiving the placebo. Elevated serum triglycerides, hyperostotic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P less than .001).
CONCLUSION: This low-dose regimen of isotretinoin not only is ineffective in reducing the occurrence of basal cell carcinoma at new sites in patients with two or more previously treated basal cell carcinomas but also is associated with significant adverse systemic effects.
IMPLICATION: The toxicity associated with the long-term administration of isotretinoin, even at the low dose used in this trial, must be weighted in planning future prevention trials.
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36.) Treatment and prevention of basal cell carcinoma with oral isotretinoin.
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SO - J Am Acad Dermatol 1988 Jul;19(1 Pt 2):176-85
AU - Peck GL; Di Giovanna JJ; Sarnoff DS; Gross EG; Butkus D; Olsen TG;
Yoder FW
PT - JOURNAL ARTICLE
AB - Twelve patients with multiple basal cell carcinomas resulting from varying causes were treated with high-dose oral isotretinoin (mean daily dosage: 3.1 mg/kg/day) for a mean of 8 months. Of the 270 tumors monitored in these patients, only 8% underwent complete clinical and histologic regression. All patients developed moderate to severe acute toxicities, leading five patients to withdraw from the study. Retinoid skeletal toxicity was identified in two patients who were examined after long-term therapy. Lower doses of isotretinoin (0.25 to 1.5 mg/kg/day) were ineffective for chemotherapy but demonstrated a chemopreventive effect in a subset of three patients who received these lower doses for 3 to 8 years. Two of these three patients have been observed after discontinuation of therapy. In one patient with a history of arsenic exposure, only one new tumor has appeared in a 27-month posttreatment observation period; in the other patient with the nevoid basal cell carcinoma syndrome, 29 new tumors have appeared within a 13-month period. This suggests that the need for long-term maintenance therapy with isotretinoin for chemoprevention of basal cell carcinoma may depend on the underlying cause of the skin cancers.
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37.) Chemoprevention of basal cell carcinoma with isotretinoin.
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SO - J Am Acad Dermatol 1982 Apr;6(4 Pt 2 Suppl):815-23
AU - Peck GL; Gross EG; Butkus D; Di Giovanna JJ
PT - JOURNAL ARTICLE AB -
Three patients with multiple basal cell carcinomas, due either to excessive sunlight exposure, the nevoid basal cell carcinoma syndrome, or arsenical insecticide exposure, were treated with oral isotretinoin for 2 1/2 to 4 years. Although higher doses were used initially, approximately 1.5 mg/kg/day was used for long-term therapy in all three patients. Therapeutic effects on existing tumors varied between each patient, and only nine of sixty-five lesions underwent complete clinical regression. No tumors enlarged in two patients; a few tumors enlarged slightly in the third patient, particularly during the later courses of therapy when isotretinoin was given at lower dosage. No new lesions have been observed in any of these three patients. With these encouraging preliminary data, it now may be appropriate to perform larger trials for longer periods of time to determine the usefulness of isotretinoin in the chemoprevention of basal cell carcinoma in patients with multiple tumors.
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38.) Chemoprevention of skin cancer in xeroderma pigmentosum.
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SO - J Dermatol 1992 Nov;19(11):715-8
AU - Kraemer KH; Di Giovanna JJ; Peck GL
PT - JOURNAL ARTICLE
AB - Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000-fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre-existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13-cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5-fold after the drug was discontinued (New Engl J Med 318: 1633-1637, 1988). Toxicity (cutaneous, triglyceride, liver-function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients.
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39.) Relative importance of prior basal cell carcinomas, continuing sun exposure, and circulating T lymphocytes on the development of basal cell carcinoma.
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SO - J Invest Dermatol 1992 Aug;99(2):227-31
AU - Robinson JK; Rademaker AW
PT - JOURNAL ARTICLE
AB - This 36-month prospective study of a group of 61 people at high risk to develop multiple basal cell carcinomas (BCC) examined the circulating lymphocyte subsets of the population, patterns of sun exposure, and the longitudinal development of basal cell carcinoma. Sun exposure status was highly correlated with immune status defined by the CD4/CD8 T-lymphocyte ratio. There were significantly more BCC at 18 and 36 months in the 35 patients with high sun exposure and low CD4/CD8 ratio than in the 20 patients with low sun exposure and high CD4/CD8 ratio. A multivariate analysis assessed the relative importance of prior basal cell carcinoma, sun exposure, and immune status on the development of the skin cancer. Basal cell carcinoma developing in the previous 18 months and sun exposure during those 18 months were the first and second most important variables in determining development of basal cell carcinoma during the next 18 months. CD4/CD8 ratio had no additional predictive ability once prior skin cancers and sun exposure were accounted for. A low ratio of CD4/CD8 cells correlated with high sun exposure during the preceding 18 months.
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40.) Topical tretinoin in actinic keratosis and basal cell carcinoma.
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SO - J Am Acad Dermatol 1986 Oct;15(4 Pt 2):829-35
AU - Peck GL
PT - CLINICAL TRIAL; JOURNAL ARTICLE
AB - In several studies between 1962 and 1978, topical tretinoin was proved capable of producing complete regression of actinic keratosis and basal cell carcinoma. But because its efficacy is not comparable to that of other modalities, topical tretinoin is currently used only as an adjunct to topical 5-fluorouracil in the treatment of actinic keratosis. One recent report found topical tretinoin ineffective in the chemoprevention of actinic keratosis. Although the oral synthetic retinoids isotretinoin and etretinate have been used in the prevention and treatment of cutaneous malignancy, the potential exists for chronic toxicity from the prolonged systemic therapy that appears necessary for maintaining the chemopreventive effect. For this reason, it may be appropriate to study further the preventive as well as therapeutic effects of topical tretinoin and other retinoids for actinic keratosis and skin cancer. If they prove safe and effective, the use of topical retinoids in the prevention and treatment of cutaneous tumors may be the most significant clinical application of these drugs.
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41.) Margin assessment of selected basal cell carcinomas utilizing laser
Doppler velocimetry.
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SO - Int J Dermatol 1993 Apr;32(4):290-2
AU - Kirsner RS; Haiken M; Garland LD
PT - JOURNAL ARTICLE
AB - BACKGROUND. Basal cell carcinomas (BCC) have increased vasculature, therefore, blood flow within the tumor may be greater than normal surrounding skin. We attempted to detect the difference in blood flow between the tumor and uninvolved surrounding skin utilizing laser doppler velocimetry (LDV).
METHODS. Ten patients with 14 BCC were studied. Using LDV, we calculated the size of the tumor based on margin assessment as predicted by the measured difference in blood flow and compared this size with the clinically predicted size and the size of the defect after Mohs micrographic surgery (MMS).
RESULTS. Clinical evaluation of tumor size prior to MMS did not correlate with the size of the surgical defect after MMS; however, correlation was found between the predicted size of the tumor as determined by LDV and the defect after MMS.
CONCLUSIONS. Tumor size of BCC as predicted by measured differences in blood flow using LDV correlated with the size of the surgical defect after MMS. This suggests that LDV was able to detect the difference in blood flow between the tumor and uninvolved surrounding skin.
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42.) Carbon dioxide laser vaporization and curettage in the treatment of large or multiple superficial basal cell carcinomas.
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SO - J Dermatol Surg Oncol 1987 Feb;13(2):119-25
AU - Wheeland RG; Bailin PL; Ratz JL; Roenigk RK
PT - JOURNAL ARTICLE
AB - Many of the standard forms of therapy for large or multiple superficial basal cell carcinomas are limited by significant postoperative pain, excessive scarring, and prolonged wound healing time. Combining traditional curettage with carbon dioxide laser vaporization creates a procedure that allows excellent visualization, due to the bloodless surgical field produced by the laser, minimal nonspecific thermal damage, rapid healing, and diminished postoperative pain. In addition, the speed and ease with which this procedure can be performed allow successful treatment of many lesions in a single outpatient session. We wish to report our results using this technique for the treatment of 52 patients with 370 superficial basal cell carcinomas.
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43.) The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma.
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SO - J Am Acad Dermatol 1992 Nov;27(5 Pt 1):723-8
AU - Orenberg EK; Miller BH; Greenway HT; Koperski JA; Lowe N; Rosen T; Brown DM; Inui M; Korey AG; Luck EE
PT - CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
AB - BACKGROUND:
Basal cell carcinomas (BCCs) are usually treated with ablative procedures. A nonsurgical treatment alternative would be of value in selected patients. OBJECTIVE: We evaluated the safety and efficacy of a new preparation for intralesional sustained-release chemotherapy with MPI 5003, 5-Fluorouracil Therapeutic Implant, for treatment of BCCs.
METHODS:
Two doses of intralesional MPI 5003 (0.25 and 0.5 ml) were compared in a double-blind study of 20 patients with biopsy-proven BCC. One BCC per patient was treated weekly for up to 6 weeks and followed up monthly for 3 months until excisional biopsy for histologic examination. Before excision the cosmetic appearance of the test site was graded.
RESULTS:
Eighty percent of 10 BCCs treated with 0.5 ml of MPI 5003 had histologically confirmed cures as compared with 60% of 10 tumors treated with the lower dose (0.25 ml). Cosmetic assessments before excision were typically good to excellent. No systemic side effects occurred.
CONCLUSION:
Results indicate the potential of MPI 5003 for targeted local chemotherapy for BCC.
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44.) Cryosurgery and topical fluorouracil: a treatment method for widespread basal cell epithelioma in basal cell nevus syndrome.
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SO - J Dermatol 1993 Aug;20(8):507-13
AU - Tsuji T; Otake N; Nishimura M
PT - JOURNAL ARTICLE
AB - A 58-year-old man with basal cell nevus syndrome had variously sized basal cell epitheliomas (BCEs), mostly of the superficial type, on his chest, back, and lumbar areas. BCEs on the lumbar area were treated with 5-fluorouracil (5-FU) cream which was applied daily under occlusive dressings (ODT). Complete erosion occurred in the center, but not at the periphery of the lesions. In the latter regions, BCE remained. Then cryosurgery (cryo) followed by topical 5-FU (cryo + 5-FU) was tried to treat the peripheral, non-eroded lesions; this caused complete erosions. Biopsy specimens obtained 6 months after epithelization did not show any evidence of recurrence. We also tried either cryo alone or cryo + 5-FU on the chest lesions, and either 5-FU alone or cryo + 5-FU on the abdominal lesions. Cryo alone or 5-FU alone could not clear BCE, but cryo + 5-FU could. These results suggest that the cryo + 5-FU was the most effective of these therapies.
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45.) Selective cytotoxic effect of topical 5-fluorouracil.
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SO - Arch Dermatol 1983 Sep;119(9):774-83
AU - Dillaha CJ; Jansen GT; Honeycutt WM; Bradford AC
PT - JOURNAL ARTICLE
AB - As an investigative procedure, a hydrophilic ointment containing 20% 5-fluorouracil (5-FU) was applied to the skin of patients with extensive actinic keratoses of the face and neck, for a period of four weeks. This resulted in a selective inflammation, erosion, and disappearance of the keratoses without significant alteration of the normal skin. Transitory adverse reactions included corneal and conjunctival irritations, phototoxic reactions, and erosion of the lower lip border. No evidence of systemic absorption was detected. Only preliminary follow-up observations are available, and no conclusion can be drawn as to the long-term results.
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46.) Nodular superficial pigmented basal cell epitheliomas.
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SO - Arch Dermatol 1982 Nov;118(11):928-30
AU - Shelley WB; Wood MG
PT - JOURNAL ARTICLE
AB - Eradication of multiple nodules, papules, and plaques of pigmented basal cell epitheliomas of the back of one patient was achieved by nine months of daily treatment with 5% fluorouracil cream. Such topical chemotherapy offers the physician an alternative to surgery and radiation in treating patients who have widespread nodular superficial epitheliomas. The need for a prolonged period of treatment and follow-up is emphasized.
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47.) Metastatic basal cell carcinoma: response to chemotherapy.
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SO - J Am Acad Dermatol 1990 May;22(5 Pt 2):905-8
AU - Bason MM; Grant-Kels JM; Govil M
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma is a common cutaneous neoplasm that rarely metastasizes. Unfortunately, there is little effective treatment available when metastasis does occur. Therefore potentially promising therapies for metastatic basal cell carcinoma should be reported. We report a case of basal cell carcinoma metastatic to bone, bone marrow, and the pleural cavity in a 51-year-old woman who showed a striking, albeit brief, response to treatment with a combination of cisplatin, bleomycin, methotrexate, and 5-fluorouracil.
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48.) Basal cell carcinoma of the vulva with lymph node and skin metastasis--report of a case and review of 20 Japanese cases.
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SO - J Dermatol 1995 Jan;22(1):36-42
AU - Mizushima J; Ohara K
PT - JOURNAL ARTICLE; REVIEW (37 references); REVIEW OF REPORTED CASES
AB - A 79-year-old Japanese woman who had basal cell carcinoma presenting as a large ulcer on her vulva with lymph node and skin metastasis is described. Histological examination revealed that tumor nests with peripheral palisading invaded deeply into the subcutaneous tissue and were accompanied by marked mucinous changes and fibrous reaction. Vascular invasion was also observed. There were inguinal lymph node metastases and two papular skin metastases on her right thigh. The primary tumor and the metastases were excised. The defect was repaired by bilateral gracilis musculo cutaneous flaps and a skin graft. We surveyed the literature and found 20 cases of metastasizing basal cell carcinoma in Japan.
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49.) Basal cell carcinoma of the scalp resulting in spine metastasis in a black patient.
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SO - J Am Acad Dermatol 1994 Nov;31(5 Pt 2):916-20
AU - Oram Y; Orengo I; Alford E; Green LK; Rosen T; Netscher DT
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma (BCC), the most common skin cancer in the United States, is locally invasive but has a low risk of metastasis. BCC is rare in black patients but, regardless of racial origin, most BCC occurs on sun-exposed areas. We describe a 67-year-old black man with a large BCC on the hairy scalp, a relatively sun-protected area, that metastasized to the spine. To our knowledge, this is the first description of a black patient with development of metastatic BCC on an otherwise normal scalp.
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50.) Long-term survival following bony metastases from basal cell carcinoma. Report of a case.
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SO - Arch Dermatol 1986 Aug;122(8):912-4
AU - Hartman R; Hartman S; Green N
PT - JOURNAL ARTICLE
AB - A patient with recurrent basal cell carcinoma developed cervical-vertebral and epidural metastases. He received palliative irradiation and had a durable remission for three years. With relapse, he underwent a laminectomy and chemotherapy and remained asymptomatic at 54 months following the diagnosis of bony metastases. To our knowledge, he is the longest reported survivor with bony metastases and is illustrative of the potential survival advantage from palliative therapy.
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51.)Giant basal cell carcinoma with metastasis and secondary amyloidosis: report of case.
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SO - Acta Derm Venereol 1983;63(6):564-7
AU - Beck HI; Andersen JA; Birkler NE; Ottosen PD
PT - JOURNAL ARTICLE
AB - Basal cell carcinoma of the skin is a slow growing relatively benign tumor usually located on the head and neck. Although rare, metastasis to lymph nodes or parenchymatous organs has been reported previously (1-9). We wish to add another case of metastasizing basal cell carcinoma of the skin, which presented certain unique features only rarely reported (1), namely complicating amyloidosis in the kidneys, the lymph nodes, the spleen and probably in the intestinal canal.
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52.) Pulmonary metastases from a basal cell carcinoma.
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SO - J Cutan Pathol 1981 Jun;8(3):235-40
AU - Keenan R; Hopkinson JM
PT - JOURNAL ARTICLE
AB - Although basal cell carcinomas are the commonest malignant condition of the skin (Borel 1973) pulmonary metastases are rare; it appears that only 30 authenticated cases have been reported (Sakula 1977). A further case is described of a man aged 64 who presented severe dyspnoea and who for 12 years had harbored an untreated ulcerating lesion of the abdominal wall shown histologically to be a basal cell carcinoma. Chest radiography showed metastatic disease confirmed histologically to be identical to the ulcerating skin lesion. Unfortunately, because of the severe respiratory condition, no definitive treatment was indicated and the patient died of respiratory failure 2 weeks following discharge.
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53.) Nonrecurrent primary basal cell carcinoma of the lower extremity with late metastasis.
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SO - J Dermatol Surg Oncol 1994 Jul;20(7):490-3
AU - Siegle RJ; Wood T
PT - JOURNAL ARTICLE
AB - BACKGROUND.
Metastatic basal cell carcinoma (MBCC) is rare, with most cases of head and neck origin and from large multi-recurrent tumors. MBCC is very rare from lower extremities and even more rare from primary tumors that were small and treated without local recurrence.
OBJECTIVE.
This paper presents a case of MBCC in a 78-year-old woman who had previously undergone resection without local recurrence of a small lower extremity basal cell carcinoma.
CONCLUSION.
MBCC can present atypically with site of origin on lower extremities, initial tumor size small, and nonrecurrence of the primary tumor site. The clinician should be aware of this as well as understand that prompt and aggressive surgical therapy to localized metastases may extend survival.
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54.) [Metastatic basal cell carcinoma]
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SO - Ann Dermatol Venereol 1993;120(2):135-8
AU - Beaulieu-Lacoste I; Joly P; Ruto F; Thomine E; Fusade T; Chevallier B; Ortoli JC; Lauret P
MC - English Abstract
PT - JOURNAL ARTICLE; REVIEW (16 references); REVIEW OF REPORTED CASES
AB - A case of basal cell carcinoma in a 17-year old male patient complicated, 5 years later, by inguinal and pulmonary metastases is reported. This clinical case raises two problems: the reality of the entity and the long-term follow-up of this type of tumours.
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55.) Metastatic basal cell carcinoma: report of twelve cases with a review of the literature [see comments]
============================================================
SO - J Am Acad Dermatol 1991 May;24(5 Pt 1):715-9
AU - Lo JS; Snow SN; Reizner GT; Mohs FE; Larson PO; Hruza GJ
PT - JOURNAL ARTICLE; REVIEW (67 references); REVIEW, TUTORIAL
AB - Metastatic basal cell carcinoma was found in 12 patients at the University of Wisconsin Mohs Surgery Clinic during the period 1936 to 1989. All patients were white men. The time of onset of the primary tumor ranged from childhood to 71 years. Eleven patients had previous treatment for basal cell carcinoma; two patients had received x-ray radiation to the face for teenage acne. The locations of the primary basal cell carcinomas were the face (n = 10), back (n = 1), and arm (n = 1). The primary tumors ranged from 3.6 x 3.0 to 20.0 x 7.0 cm. The interval from onset to the first sign of metastases ranged from 7 to 34 years. In all cases, the primary tumor was histologically identical to the metastatic lesion. Perineural extension of the basal cell carcinoma in the primary lesion was found in five cases. Regional lymph nodes were the most frequent site of metastasis. Treatment consisted of a combination of surgery, radiation, and chemotherapy. Only two patients survived more than 5 years after surgical treatment. One patient has survived 25 years and is still alive.
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56.) Rapid development of metastases from basal cell carcinoma presenting as cranial nerve palsies.
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SO - J Dermatol Surg Oncol 1988 Dec;14(12):1410-2
AU - Ambros RA; Standiford SB; Sobel HJ; Haim A; Mohit-Tabatabai MA
PT - JOURNAL ARTICLE
AB - A case is reported of metastatic basal cell carcinoma presenting with multiple neurologic deficits 20 months after excision of the primary lesion with good local control. Many features associated with the development of metastasis from basal cell carcinoma were not present in this case.
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57.) Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study.
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Acta Derm Venereol 1999 May;79(3):204-6
Soler AM, Warloe T, Tausjo J, Berner A
Photodynamic Out-patient Clinic, Department of Surgical Oncology, The Norwegian Radium Hospital, Oslo.
Fifty-eight patients with 119 nodular (2 mm or more in thickness) basal cell carcinomas successfully treated with photodynamic therapy were included in this 1-year follow-up study. The initial cure rate at 3-6 months was 92% after photodynamic therapy, which included an initial debulking procedure and topical application of dimethylsulphoxide in order to enhance penetration of 5-aminolevulinic acid (20% in cream) to which the lesions were exposed for 3 h prior to exposure to light. At examination 12-26 months (mean 17 months) after treatment 113 lesions (95%) were still in complete response. Six lesions (5%) had recurred, located on the face, scalp and ear. The cosmetic outcome was evaluated as excellent to good in 91%. Microscopic examination of biopsies taken from healed areas in 7 patients did not reveal any sign of damage in 5 and only minor alterations in 2.
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58.) Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmstead County, Minnesota.
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Ophthalmology 1999 Apr;106(4):746-50
Cook BE Jr, Bartley GB
Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
OBJECTIVE: To determine the epidemiologic and clinical characteristics of patients with malignant eyelid tumors in an incidence cohort. DESIGN: Cohort series.
PARTICIPANTS: A computerized retrieval system was used to identify all patients residing in Olmsted County, Minnesota, who had a newly diagnosed malignant eyelid tumor during the 15-year interval from 1976 through 1990. The patients' medical records were reviewed for demographic and clinical data.
INTERVENTION: Surgical excision with frozen-section histopathologic analysis, Mohs' micrographic excision, and electrodesiccation and curettage were the primary methods of treatment.
MAIN OUTCOME MEASURES: Survivorship free of tumor.
RESULTS: The incidence cohort included 174 patients who each had 1 tumor; men and women were equally affected, and all patients were white. Tumors developed most commonly on the lower eyelid (n = 85; 48.9%) and in the medial canthal region (n = 48; 27.6%) but involved the right and left sides with equal frequency. Of the 174 tumors, 158 were basal cell carcinomas (90.8%), 15 were squamous cell carcinomas (8.6%), and 1 (0.6%) was a malignant melanoma. The age- and gender-adjusted incidence rates for basal cell carcinoma, squamous cell carcinoma, and malignant melanoma were 14.35, 1.37, and 0.08 per 100,000 individuals per year, respectively. No cases of sebaceous gland carcinoma were identified. The 5- and 10-year recurrence rates for all tumors on the eyelid were 2% and 3%, respectively. The probability of an unrelated malignancy developing elsewhere in the body was approximately 9% at 5 years and 15% at 10 years.
CONCLUSIONS: Basal cell carcinoma is the most common malignant eyelid tumor in whites. The lower eyelid and medial canthus are the most frequent sites of origin. Men and women are equally affected. Recurrence after surgical excision is uncommon.
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59.) Does wound healing contribute to the eradication of basal cell carcinoma following curettage and electrodessication?
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Dermatol Surg 1999 Mar;25(3):183-7; discussion 187-8
Nouri K, Spencer JM, Taylor JR, Hayag M, DeVoursney J, Shah N Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami Veterans Affairs Medical Center, Florida, USA.
BACKGROUND:
Histologic studies indicate that C&D fails to mechanically remove all the tumor in a percentage of cases that far exceeds the 5-year recurrence rate. This raises the question that if C&D does not mechanically remove the tumor in a significant number of patients, why don't we observe tumor recurrence in most of these patients? Our previous study indicates that inflammation occurring over 1 month following C&D does not clear residual tumor. It may be some other process, requiring more time, that clears the residual tumor. Perhaps the proliferative or maturation phase of wound healing or, alternatively, a slow-acting process such as a low-grade immune response set in motion earlier, clears the residual tumor.
OBJECTIVE:
To test the hypothesis that wound healing and maturation following C&D clear residual tumor that has not mechanically removed by the procedure. METHODS: The frequency of residual BCC detected histologically immediately following C&D was compared with the frequency 3 months after
the C&D, an amount of time in which the maturation phase of wound healing is well under way.
RESULTS:
Twenty-two of 29 primary BCC less than 1 cm in size were tumor-free immediately following the procedure (clearance rate 75.9%). Twelve primary BCC <1 cm were treated by C&D, allowed to heal for 3 months, and then excised and checked histologically. Ten of the twelve BCC were free of tumor, for a clearance rate of 83.3%, which is not a statistically significant difference (p = 0.7187).
CONCLUSION:
By 3 months, the proliferative phase of wound healing is complete, and our study indicates that this phase has no effect on clearing the tumor. The maturation phase is well under way three months following C&D, and no statistically significant
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60.)Does inflammation contribute to the eradication of basal cell carcinoma following curettage and electrodesiccation?
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Dermatol Surg 1997 Aug;23(8):625-30; discussion 630-1
Spencer JM, Tannenbaum A, Sloan L, Amonette RA Division of Dermatology, University of Tennessee, Memphis, USA.
BACKGROUND: Curettage and electrodesiccation (C&D) is probably the technique most frequently utilized by dermatologists to treat basal cell carcinomas (BCC). From histologic studies, it appears C&D does not completely mechanically remove all nests of BCC in a substantial number of cases. Nevertheless, the reported 5-year reoccurrence rate following C&D is significantly less than this histologically observed residual tumor frequency immediately following C&D. Among the multiple possibilities that exist to explain why these residual nests do not appear as recurrent tumor more frequently is the theory that inflammation developing after C&D clears residual tumor.
OBJECTIVE: To test the hypothesis that inflammation developing after C&D clears residual tumor not mechanically removed by the procedure.
METHODS: The frequency of residual BCC detected histologically immediately following C&D was compared with the frequency 1 month after the C&D, an amount of time in which an effect (if any) of inflammation could occur.
RESULTS: Twenty-two of 29 primary BCC < 1 cm treated by C&D were tumor free immediately following the procedure (clearance rate, 75.9%). Eleven of 14 primary BCC < 1 cm treated by C&D then allowed to granulate 1 month before excision and histologic analysis were tumor free, for a clearance rate of 78.6%. Examination of larger tumors immediately following C&D revealed size is a significant variable for clearance rates. Eleven primary BCC > 1 cm but < 2 cm were examined histologically immediately following C&D; only three were tumor free for a clearance rate of 27.3%. Only one of five tumors > 2 cm thus treated was tumor free, for a clearance rate of 20%. Nine recurrent BCC of various sizes were treated by C&D and immediately examined histologically. Two were tumor free for a clearance rate of 22.2%. Two recurrent BCC were allowed to heal 1 month following C&D; one of these was tumor free when excised.
CONCLUSION: For primary BCC < 1 cm, no evidence was found that inflammation occurring over 1 month following C&D clears residual tumor. It was also noted that C&D fails to completely remove tumor in a large majority of primary BCC > 1 cm, and in recurrent BCC.
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61.) Cryosurgery in dermatology.
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Eur J Dermatol 1998 Oct-Nov;8(7):466-74
Zouboulis CC Department of Dermatology, University Medical Center Benjamin Franklin,
The Free University of Berlin, Hindenburgdamm 30, D-12 200, Berlin, Germany.
zoubbere@zedat.fu-berlin.de
The aim of this article is to provide current information on the clinical development of cutaneous cryoreaction and the indications, complications and contraindications of cutaneous cryosurgery. Successful cutaneous cryosurgery requires rapid freezing and slow thawing, minimum tissue temperatures of -25 degrees C to -60 degrees C and, in malignant lesions, repeated freeze-thaw cycles. Frozen tissue reacts with peripheral erythema immediately following thawing, and consequently with oedema, bulla formation, exudation, mummification, and usually heals with a fine atrophic scar within a 4-week period. Cryosurgery is now considered the treatment of choice in hypertrophic scars and keloids, granuloma annulare and capillary haemangioma of the newborn. It also represents a valuable alternative therapy for various skin diseases, including common warts, solar lentigo, actinic keratoses, superficial basal cell carcinoma and Kaposi's sarcoma. Cryosurgery is a safe regimen with only a few adverse effects and contraindications. Pain during and/or shortly after treatment, bulla formation and local oedema are the major, temporary adverse effects; lesional hypopigmentation and/or peripheral hyperpigmentation is the most common by occurring long-term complication.
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62.) [The treatment of basal cell carcinoma patients by dermatologists in Netherland].
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Ned Tijdschr Geneeskd 1998 Jul 4;142(27):1563-7
Thissen MR, Neumann HA, Berretty PJ, Ideler AH Academisch Ziekenhuis, afd. Dermatologie, Maastricht.
OBJECTIVE: To determine the policy of dermatologists practising in the Netherlands in the treatment of basal cell carcinoma. DESIGN: Written enquiry.
SETTING: Catharina Hospital, Eindhoven, the Netherlands.
METHOD: All 293 dermatologists practising in the Netherlands were sent a questionnaire in May 1996 containing 15 questions about diagnosis and treatment of basal cell carcinoma.
RESULTS: Eighteen forms dropped off because of termination of the practice or joint completion in group practices. The response was 76% (208/275). The diagnosis was made usually on the basis of histological examination (71% of the respondents; 84% in a tumour recurrence). Excision was the preferred treatment for all subtypes of basal cell carcinoma; second choices were cryosurgery or curettage/electrocoagulation. Roentgen contact therapy has been practically abandoned. New methods such as photodynamic therapy and immunotherapy are being used only sporadically on an experimental basis. Most dermatologists regarded tumour recurrences as a bigger problem than primary tumours. They attempt to reduce the percentage of recurrences by giving advice about risk factors (sunlight).
CONCLUSION: Too little use is being made of diagnostic biopsy to enable an optimal choice of therapy of basal cell carcinomas, especially in cases of recurrence tumours.
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63.) [Therapy of non-melanocytic skin tumors].
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Ther Umsch 1998 Aug;55(8):515-21
Hafner J Dermatologische Klinik und Poliklinik, Universitatsspital Zurich.
Actinic keratosis on sun-damaged skin are very common in individuals with fair complexion. Management encompasses cryosurgery, tretinoin or 5-fluorouracil-cream. Bowen's disease, however, requires surgical excision or radiotherapy. Basal cell carcinoma and squamous cell carcinoma are the two most common malignant skin tumours in Western Europe. Typically these tumours can be managed either by excision and primary wound closure, by cryosurgery or by radiotherapy.
The method of choice is determined by the type and location of the tumour and the general condition of the patient. For more difficult-to-treat malignant skin tumours surgical resection with histological margin control is required. Mohs' micrographic surgery is a specialized procedure. This method entails to a full work-up of the excisional margins.
The defect is closed only after histological verification of tumour-free surgical margins. Difficult-to-treat tumours are recurrent, sclerodermiform and large (diameter more than 20 mm) basal cell carcinomas. Indications for margin control in squamous cell carcinomas are tumours with more than 20 mm of diameter, with more than 5 mm thickness and with poor histologic differentiation (Broders grade III and IV, desmoplastic squamous cell carcinoma). Therefore, a skin biopsy is often required to plan the optimal treatment of a malignant skin tumour. The collaboration of primary care providers and specialists is beneficial in the management of difficult skin tumours.
Renal transplant recipients under immunosuppression are prone to have squamous cell carcinoma of a more aggressive type. Dermatofibrosarcoma protuberans is another good indication for Mohs' micrographic surgery. A regular follow-up for recurrences or secondary tumours, as well as an effective secondary prevention of sun damage are important for skin cancer patients.
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64.) [High resolution ultrasound imaging: value in treatment of basocellular carcinoma by cryosurgery].
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Ann Dermatol Venereol 1998 Aug;125(8):500-4
Vaillant L, Grognard C, Machet L, Cochelin N, Callens A, Berson M, Aboumrad J, Patat F, Lorette G Service de Dermatologie, CHU Tours.
OBJECTIVE: We conducted a prospective evaluation of the contribution of high-resolution ultrasound imaging prior to cryosurgery for basocellular carcinoma and in search for recurrence.
PATIENTS AND METHODS: All patients seen between 1992 and 1994 at the skin tumor clinic and treated by cryosurgery were included. Ultrasound imaging using 20 MHz prototype was performed prior to cryosurgery and 2 months later.
RESULTS: Among 101 patients treated, 112 basocellular carcinomas were treated by cryosurgery. Ultrasound imaging provided good visualization of the tumor limits in all cases. The ultrasound aspect was anechogenic, often with rare areas of highly dense echoes. The tumor limits described by ultrasound imaging were larger than the clinical limits in 32% of the cases. In 8 of the 16 cases of recurrent tumors, the ultrasound examination revealed the recurrence first. In the other 8 cases, clinical manifestations were confirmed by ultrasonography. In our series, recurrence of basocellular carcinoma was statistically more frequent when the depth of the tumor was 3 mm (ultrasonographic measurement) or when the lateral limits established by ultrasound assessment were greater than the clinical evaluation.
DISCUSSION:
These findings demonstrate that high-resolution ultrasound imaging of basocellular carcinomas prior to cryosurgery: 1) visualizes tumor limits allowing adapted cryosurgery, 2) identifies factors with predictive value for recurrence, 3) can identify recurrences early. Ultrasound imaging of the skin is a useful non-invasive technique for pre- and post-therapeutic assessment of skin tumors and could be a particularly useful tool for "blind" cryosurgery destruction of skin tumors.
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65.) Recurrent basal cell carcinoma treated with cryosurgery.
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J Am Acad Dermatol 1997 Jul;37(1):82-4
Kuflik EG, Gage AA Department of Dermatology, University of Medicine and Dentistry, New
Jersey Medical School, Newark, USA.
BACKGROUND: Although there are reports of cure rates achieved by cryosurgery for primary basal cell carcinomas (BCCs), there are few data on the cryosurgical treatment of recurrent BCCs.
OBJECTIVE: Our purpose was to discuss case selection, cryosurgical management, and results of therapy.
METHODS: Cryosurgery was performed in 54 patients with 56 recurrent BCCs. The treatment consisted of aggressive freezing including an adequate margin of surrounding tissue.
RESULTS: Wound healing was favorable and the cosmetic results were excellent. Two recurrences were found and were referred for Mohs micrographic surgery.
CONCLUSION: We conclude that cryosurgical treatment of selected recurrent BCCs yields results that compare favorably with other methods of treatment.
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66.) Fractional cryosurgery. A new technique for basal cell carcinoma of the eyelids and periorbital area.
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Dermatol Surg 1997 Jun;23(6):475-81
Goncalves JC Department of Dermatology, Hospital Distrital de Santarem, Portugal.
BACKGROUND: Cryosurgery is an established method to treat malignant tumors of the eyelids and periorbital area. Nevertheless, it has been abandoned for tumors greater than 10 mm, because it gives irregular esthetic results and, in some cases, lagophthalmos. OBJECTIVE: To devise a new method for the treatment of such tumors.
METHOD: Fractional cryosurgery is performed in stages: the center of the lesion is frozen, resulting in a reduction of the tumor; this procedure is repeated, as necessary, until the lesion's diameter is smaller than 10 mm; the standard cryosurgical procedure is then carried out.
RESULTS: The treatment of the first 20 basal cell carcinomas with diameters between 10 and 24 mm is described, with excellent clinical and cosmetic results.
CONCLUSION: With fractional cryosurgery, the final scar bears no relation to the size of the original tumor but, instead, corresponds to the size of the lesion preceding the final cryosurgical procedure.
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67.) Long-term follow-up of cryosurgery of basal cell carcinoma of the eyelid.
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J Am Acad Dermatol 1997 May;36(5 Pt 1):742-6
Lindgren G, Larko O Department of Ophthalmology Goteborg University, Sahlgrenska Hospital, Sweden.
BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant tumor of the eyelid and its incidence is increasing. It remains to be established which is the best treatment in terms of safety and cost-effectiveness.
OBJECTIVE: Our purpose was to analyze the long-term treatment results and possible side effects of cryosurgery of eyelid BCC.
METHODS: During the last 14 years 219 patients (222 tumors) treated for eyelid BCC with cryosurgery were followed up prospectively for up to 10 years.
RESULTS: The tumors cleared completely after treatment in all patients with no recurrence observed to date. Ninety-two patients were followed up for 5 years or more. Complications were few and minor. In 26 treated eyelids conjunctival overgrowth was noted.
CONCLUSIONS: We conclude that cryosurgery of BCC of the eyelid has a high cure rate, is cost-effective, and is well tolerated.
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68.) Five-year results of curettage-cryosurgery of selected large primary basal cell carcinomas on the nose: an alternative treatment in a geographical area underserved by Mohs' surgery.
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Br J Dermatol 1997 Feb;136(2):180-3
Nordin P, Larko O, Stenquist B Department of Dermatology, Lundby Hospital, Goteborg, Sweden.
Mohs' micrographic surgery (MMS) is the recommended treatment for large basal cell carcinomas (BCCs) of the nose. This 5-year follow-up study attempts to evaluate whether curettage-cryosurgery (CC) could be an alternative therapy in a country where optimal resources for MMS are lacking. All patients with a primary nasal or perinasal BCC, 10 mm or larger in diameter, were assessed at a skin tumour clinic. Sixty-one BCCs of non-morphoeiform type were treated with CC. Most of the tumour was removed by careful curettage with different sized curettes. The tumour area was then frozen with liquid nitrogen in a double freeze-thaw cycle. Fifty patients were followed for at least 5 years with only one recurrence. The cosmetic result was good or acceptable in all patients. A thorough curettage followed by cryosurgery could be a safe and inexpensive alternative therapy even for large primary non-morphoeiform BCCs of the nose.
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69.) Laser microsurgery for superficial T1-T2 basal cell carcinoma of the eyelid margins.
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Ophthalmology 1997 Jul;104(7):1179-84
Bandieramonte G, Lepera P, Moglia D, Bono A, De Vecchi C, Milani F Division of Surgical Semiotics and Ambulatory Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
BACKGROUND:
Basal cell carcinoma (BCC), the most common malignancy of the eyelid margins, poses therapeutic problems. Surgery, radiation therapy, and cryotherapy are the currently accepted methods for the treatment of this affliction. To verify the technical and clinical effectiveness of the surgical laser method, a specific approach was developed by performing laser-combined procedures under microscopic control.
METHODS:
A series of 26 patients underwent carbon dioxide (CO2) laser microsurgical excision of 27 primary superficial BCCs of the eyelid margins. Eighteen tumors were T1 and 9 were T2. The lesions were located at the lid margins in 18 and at the canthus in 9 cases. The eyelash line was involved in all cases, whereas intermarginal space was involved in 17 cases, without extension to the conjunctival border. Six lesions were in the lacrimal region. Median linear extent of the lesion was 5 mm (range, 4-10 mm). Treatment was performed with the patient under local anesthesia in a Day Hospital regimen. The authors used the microscope-mounted CO2 laser as a scalpel to excise the tumor mass, thus obtaining the specimen for histologic evaluation. The authors treated the deep and lateral resection margins with laser vaporization and left the wound bed to heal by secondary intention.
RESULTS:
No significant complications were observed. As full-thickness eyelid resections were avoided, the authors noted conservation of lid function and cosmetic aspect in all patients. With a median follow-up of 73 months (range, 18-118), only one patient had tumor recurrence after 22 months. This tumor, located at the outer canthus, had a second microsurgical laser excision, and the patient is disease free 51 months after the last treatment.
CONCLUSIONS:
Laser microsurgery appears to be a safe and effective treatment method for primary superficial T1 and T2 BCC of the eyelid margins without conjunctival extension.
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70.)[Use of Nd:YAG laser for treatment of basal-cell carcinomas and some premalignant conditions].
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Przegl Dermatol 1990 Nov-Dec;77(6):385-8
Rubisz-Brzezinska J, Bendkowski W Katedry i Kliniki Dermatologii Sl. AM w Katowicach.
In 51 patients, 29 female and 22 male of average 61 years old, 94 lesions were treated with Nd: YAG laser; 70 basal-cell carcinomas, 9 superficial basal-cell carcinomas, 12 actinic keratosis and 3 cutaneous horns. Size of changes varied from 7 to 24 mm. Quantity of energy used in laser-therapy was dependent on diagnosis, focus size, location and amounted from 50 to 240 J/cm2. Authors are of the opinion that Nd:YAG laser-therapy is a very good method for treatment of skin tumors. Moreover, the advantage of this method is its possibility of a single procedure in the conditions of outpatients clinic.
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71.) Laser therapy of skin tumors.
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Recent Results Cancer Res 1995;139:417-21
Landthaler M, Szeimies RM, Hohenleutner U Department of Dermatology, University of Regensburg, Germany.
Malignant skin tumors can be treated by CO2 laser excision or vaporization, neodymium: yttrium aluminum garnet (Nd:YAG) laser coagulation, and systemic or topical photodynamic therapy (PDT). Possible indications for CO2 laser vaporization include superficial basal cell carcinomas, actinic keratoses, Bowen's disease, actinic cheilitis, and leukoplakias. The Nd:YAG laser may be used for coagulation of basal cell carcinomas, squamous cell carcinomas, Kaposi's sarcoma, and metastatic skin tumors. Systemic and topical PDT is still an experimental modality and is mostly applied for treatment of basal cell carcinomas. However, laser treatment of skin tumors is not yet considered as standard therapy and should be confined to selected patients. Further clinical studies are necessary to determine the role of laser therapy in this special indication.
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72.) Treatment of superficial basal cell carcinoma and squamous cell carcinoma in situ with a high-energy pulsed carbon dioxide laser.
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Arch Dermatol 1998 Oct;134(10):1247-52
Humphreys TR, Malhotra R, Scharf MJ, Marcus SM, Starkus L, Calegari K Department of Medicine, University of Massachusetts Medical Center, Worcester, USA.
BACKGROUND:
High-energy pulsed carbon dioxide (CO2) lasers have been used extensively to resurface wrinkled and photodamaged skin with a low risk of scarring. Results of histological studies demonstrate precise ablation depths in treated skin with minimal thermal damage to underlying tissue. Our objective was to determine if a pulsed CO2 laser could effectively ablate superficial malignant cutaneous neoplasms (superficial multifocal basal cell carcinoma [BCC] and squamous cell carcinoma [SCC] in situ).
OBSERVATIONS: Thirty superficial neoplasms (17 BCCs and 13 SCCs) and their surrounding 3-mm margins were treated with either 2 or 3 passes of a pulsed CO2 laser (500 mJ, 2-4 W) using a 3-mm collimated handpiece.
The treated areas were subsequently excised and evaluated histologically by serial sectioning at 5-micron intervals for residual tumor at the deep and lateral margins. Average patient age was greater for those with SCCs than for those with BCCs (76.5 vs 56.7 years; P = .001). The average tumor thickness of SCC in situ was significantly greater than that of superficial BCC (0.57 vs 0.34 mm; P = .01). All (9 of 9 patients) BCCs were completely ablated with 3 passes, and residual tumor in the deep margins was seen in 5 of 8 patients treated with 2 passes of the pulsed CO2 laser (P = .005). Incomplete vaporization of the SCC depth was seen in 3 of 7 patients treated with 3 passes and in 2 of 6 patients treated with 2 passes. Those SCCs incompletely treated were significantly thicker than those completely ablated (0.65 vs 0.41 mm; P = .01). Positive lateral margins were seen in 1 BCC and 3 SCC specimens.
CONCLUSIONS:
Pulsed CO2 laser treatment can be effective in ablating superficial BCC. Treatment of the neoplasm and a minimum of 4-mm margins with 3 passes (500 mJ, 2-4 W) is recommended for complete vaporization using this laser system. Because 3 passes did not completely ablate all SCC in situ, use of this modality alone is not recommended for treatment of thick or keratotic lesions. No direct comparison of efficacy can be made with other destructive modalities that have not been evaluated with comparably sensitive histological techniques. Further study is needed to establish any cosmetic advantage of pulsed CO2 lasers over other destructive modalities for treatment of superficial malignant neoplasms and long-term cure rates.
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73.) Prediction of subclinical tumor infiltration in basal cell carcinoma.
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J Dermatol Surg Oncol 1991 Jul;17(7):574-8
Breuninger H, Dietz K
Department of Dermatology, University Hospital for Dermatology, Tubingen, Federal Republic of Germany.
Two thousand-sixteen basal cell carcinomas (BCCs) were documented in terms of age, anatomic location, tumor diameter, initial excision depth, safety margin, histologic type, and the position of tumor outgrowths as determined by three-dimensional histologic study of the tumor margins in paraffin sections (micrographic surgery). The extent of each subsequent excision was recorded until tumor-free tissue was reached. The results showed that BCCs have a highly irregular infiltration pattern and a predilection for small, fingerlike outgrowths whose bases occupy 1-30 degrees of the tumor circumference. When superficial extension was expressed mathematically, the resulting exponential functions varied highly significantly (P = .001) according to histologic tumor type and diameter. The resulting curves permitted very precise prediction of the probability of tumor-positive margins (ie, subtotal excision), depending on the safety margin, histologic tumor type, and tumor diameter. For example, the probability of tumor-positive margins after excision of a BCC up to 10 mm in diameter is 30% with a safety margin of 2 mm, 16% with a safety margin of 3 mm, and 5% with a safety margin of 5 mm. The probability of tumor-positive margins for fibrosing primary BCCs 10-20 mm in diameter is 48, 34, and 18% with safety margins of 2, 3, and 5 mm, respectively. Recurrent tumors have a significantly higher probability of positive margins (P = .001) than primary ones. Anatomic location and tumor age affect subclinical extension only indirectly.
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74.) Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision.
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J Dermatol Surg Oncol 1992 Jun;18(6):471-6
Silverman MK, Kopf AW, Bart RS, Grin CM, Levenstein MS Department of Dermatology, New York University School of Medicine.
This is the third report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 588 previously untreated (primary) BCCs removed by surgical excision.
The cumulative 5-year recurrence rate was 4.8%. This is a statistically significant lower recurrence rate (P = .034) than 135 previously treated BCCs that had a re-recurrence rate of 11.6%. For the primary BCCs, multivariate analysis showed that location on the head (P = .010) and being male (P = .004) were independent risk factors for recurrence. The patient's age, the duration of the BCC, its maximum diameter, or the time span (1955-1963, 1964-1972, 1973-1982) in which it was treated did not significantly affect the recurrence rate.
The 5-year recurrence rate for BCCs excised from various anatomic sites were as follows: 1) neck, trunk, and extremities = 0.7%; 2) head--less than 6 mm in diameter = 3.2%; 3) head--6 to 9 mm in diameter = 8.0% (treated since 1964 = 5.2%); and 4) head--10 mm or more in diameter = 9.0%. Surgical excision is a highly effective method for removal of BCCs, and achieved a good to excellent cosmetic outcome in about 85% of the recurrence-free treatment sites.
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75.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
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ARTICLE SOURCE: Arch Dermatol (United States), Jun 1988, 124(6) p930-4
AUTHOR(S): Obalek S; Favre M; Jablonska S; Szymanczyk J; Orth G
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Human papillomavirus-2 genomes were detected by molecular hybridization in two cases of basal cell carcinomas that developed in immunosuppressed individuals. This form of human papillomavirus is usually responsible for common warts in the general population. Although it does not appear to have oncogenic potential, it may be, in some cases, associated with cutaneous malignancy.
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76.) Occurrence of human papillomavirus type 16 DNA in cutaneous squamous and basal cell neoplasms.
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ARTICLE SOURCE: J Am Acad Dermatol (United States), Nov 1990, 23(5 Pt 1) p836-42
AUTHOR(S): Eliezri YD; Silverstein SJ; Nuovo GJ
PUBLICATION TYPE:
JOURNAL ARTICLE
ABSTRACT:
Sixty-eight cutaneous squamous cell neoplasms (in situ and invasive) and 26 basal cell carcinomas from 89 patients were analyzed for DNA sequences homologous to the human papillomavirus (HPV) types found predominantly in the genital tract. Thirty-six (53%) of the squamous cell neoplasms contained HPV DNA as detected by filter or in situ hybridization analysis. The frequency of detection of HPV DNA was dependent on the site of the lesion. Of 40 genital squamous cell neoplasms (penile, vulvar, and perianal), 27 (68%) had detectable HPV DNA. In 25 of these, the HPV type was 16 or HPV-16-related, which was similar to the results for the squamous cell neoplasms of the finger (HPV DNA in 9 of 11 tumors with HPV-16 in seven). None of 16 squamous cell neoplasms from sites other than the genital tract or the finger had detectable HPV DNA. HPV DNA was detected in one of the 26 basal cell carcinomas (4%). We conclude that, for cutaneous epithelial malignancies, HPV-16 is restricted to squamous cell neoplasms of the genital tract and finger. These data are consistent with venereal transmission of HPV-16 to the periungual region and suggests a role for this virus in the evolution of squamous cell carcinoma at this site.
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77.) Basal cell carcinoma of the genitalia.
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Dermatol Surg 1998 Dec;24(12):1361-3
Nehal KS, Levine VJ, Ashinoff R Ronald O. Perelman Department of Dermatology, New York University Medical Center, NY 10016, USA.
BACKGROUND: Basal cell carcinomas (BCC) arising on the genitalia are exceedingly rare with an unclear pathogenesis. OBJECTIVE: To better understand risk factors, tumor characteristics, and the possible role of human papillomavirus (HPV) in the development of BCC of the genitalia.
METHODS: 1543 records of Mohs micrographic surgery performed during a 6-year period were reviewed to identify cases of BCC arising on the genitalia. Tumor tissue was analyzed for HPV DNA by in situ hybridization.
RESULTS: Four patients with BCC of the genitalia were treated with Mohs micrographic surgery. The malignancies were located on the scrotum, perineum, and perianal areas in the three male patients and on the vulva in the female patient. The mean age was 67 years. None of the patients had prior history of skin cancers. Histologic evaluation of the tumors revealed two nodular subtypes, one superficial subtype, and one with follicular differentiation. In situ hybridization failed to reveal DNA of HPV types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52.
CONCLUSION: In this small series, genital BCC occurred in an older age group with no identifiable predisposing risk factors and did not show evidence of HPV infection.
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78.) Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers.
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J Invest Dermatol 1998 Jul;111(1):123-7
Harwood CA, Spink PJ, Surentheran T, Leigh IM, Hawke JL, Proby CM, Breuer J, McGregor JM Department of Academic Dermatology, Royal Hospitals NHS Trust, London, UK.
Psoralen and UVA (PUVA) photochemotherapy is associated with a dose-dependent increased risk of nonmelanoma skin cancer in patients treated for psoriasis. Like ultraviolet B radiation, PUVA is both mutagenic and immunosuppressive and may thus act as a complete carcinogen; however, the reversed squamous to basal cell carcinoma ratio (SCC:BCC) in PUVA-treated patients, also seen in immunosuppressed renal transplant recipients, suggests a possible cofactor role for human papillomavirus (HPV) infection. In this study we examine a large series of benign and malignant cutaneous lesions for the presence of HPV DNA from patients treated with high dose (> or =500 J per cm2) ultraviolet A.
A panel of degenerate primers based on the L1 (major capsid protein) open reading frame was employed, designed to detect mucosal, cutaneous, and epidermodysplasia verruciformis HPV types with high sensitivity and specificity. HPV DNA was detected in 15 of 20 (75%) non-melanoma skin cancer, seven of 17 (41.2%) dysplastic PUVA keratoses, four of five (80%) skin warts, and four of 12 (33%) PUVA-exposed normal skin samples. The majority of HPV positive lesions contained epidermodysplasia verruciformis-related HPV including HPV-5, -20, -21, -23, -24, and -38. Possible novel epidermodysplasia verruciformis types were identified in further lesions.
Mixed infection with epidermodysplasia verruciformis, cutaneous, and/or mucosal types was present in six of 30 (20%) of all HPV positive lesions, including in normal skin, warts, dysplastic PUVA keratoses, and squamous cell carcinomas. The prevalence and type of HPV infection in cutaneous lesions from PUVA-treated patients is similar to that previously reported in renal transplant-associated skin lesions, and suggests that the role of HPV in PUVA-associated carcinogenesis merits further study.
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79.)Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses.
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J Invest Dermatol 1990 Nov;95(5):537-42
Kawashima M, Favre M, Obalek S, Jablonska S, Orth G Unite des Papillomavirus, Institut Pasteur, Paris, France.
To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population.
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80.) Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.
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Arch Dermatol 1988 Jun;124(6):930-4
Obalek S, Favre M, Jablonska S, Szymanczyk J, Orth G Department of Dermatology, Warsaw School of Medicine, Poland.
Human papillomavirus-2 genomes were detected by molecular hybridization in two cases of basal cell carcinomas that developed in immunosuppressed individuals. This form of human papillomavirus is usually responsible for common warts in the general population. Although it does not appear to have oncogenic potential, it may be, in some cases, associated with cutaneousmalignancy.
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