Rosácea papulopustulosa: respuesta al tratamiento con azitromicina oral / Papulopustular Rosacea: Response to Treatment with Oral Azithromycin

INTRODUCCIÓN: El tratamiento de la rosácea papulopustulosa (RPP) ha consistido durante años en el uso de tetraciclinas orales y antibióticos tópicos. Pero no es infrecuente encontrar casos de RPP resistentes al tratamiento convencional. Azitromicina oral ha demostrado ser una opción eficaz para estos pacientes no respondedores. MATERIAL Y MÉTODO: Se realizó un estudio piloto prospectivo con 16 pacientes con RPP no respondedores al tratamiento convencional (doxiciclina oral y metronidazol gel) que recibieron tratamiento con azitromicina oral. En la visita inicial (visita 1) se realizó una valoración basal del estadio clínico de la RPP, según 4 niveles de gravedad progresiva, y se inició tratamiento con azitromicina oral. A las 8 semanas de finalizar el tratamiento (visita 2) se evaluó la respuesta clínica según 3 niveles de mejoría respecto al estadio clínico basal. Posteriormente, para evaluar la eficacia de azitromicina oral a largo plazo, se realizaron visitas periódicas cada 12 semanas. RESULTADOS: Todos los pacientes que recibieron tratamiento con azitromicina oral mejoraron de su RPP. A las 8 semanas de finalizar el tratamiento se objetivó un eritema facial residual débil o nulo, con desaparición completa de las pápulas y/o pústulas en el 87,5% de los pacientes. En cuanto al mantenimiento de la eficacia a largo plazo, únicamente 2 pacientes presentaron una recidiva de lesiones inflamatorias de RPP. CONCLUSIONES: Los resultados de nuestro estudio evidencian que azitromicina oral podría ser un fármaco de gran eficacia a corto y largo plazo para el manejo de aquellos casos de RPP resistentes al tratamiento convencional

INTRODUCTION: Oral tetracyclines and topical antibiotics have been used to treat papulopustular rosacea (PPR) for years, but it is not uncommon to find patients who do not respond to this standard treatment. In such refractory cases, oral azithromycin has proven to be an effective option. MATERIAL AND METHOD: We conducted a prospective pilot study of 16 patients with PPR who were treated with oral azithromycin after a lack of response to oral doxycycline and metronidazole gel. At the first visit, the patients were assessed for baseline severity of PPR on a 4-point clinical scale and started on oral azithromycin. At the second visit, response to treatment in terms of improvement from baseline was evaluated on a 3-point scale. Patients were then scheduled for follow-up visits every 12 weeks to assess long-term effectiveness. RESULTS: All 16 patients experienced an improvement in their PPR following treatment with oral azithromycin. Eight weeks after completion of treatment, 14 patients (87.5%) showed complete or almost complete recovery (slight or no residual redness and complete clearance of papules and pustules). Only 2 patients experienced a new episode of inflammatory PPR lesions during follow-up. CONCLUSIONS: The findings of this pilot study suggest that oral azithromycin could be a very effective short-term and long-term treatment for RPP resistant to conventional treatment

Papulopustular Rosacea: Response to Treatment with Oral Azithromycin. / Rosácea papulopustulosa: respuesta al tratamiento con azitromicina oral.

INTRODUCTION: Oral tetracyclines and topical antibiotics have been used to treat papulopustular rosacea (PPR) for years, but it is not uncommon to find patients who do not respond to this standard treatment. In such refractory cases, oral azithromycin has proven to be an effective option. MATERIAL AND METHOD: We conducted a prospective pilot study of 16 patients with PPR who were treated with oral azithromycin after a lack of response to oral doxycycline and metronidazole gel. At the first visit, the patients were assessed for baseline severity of PPR on a 4-point clinical scale and started on oral azithromycin. At the second visit, response to treatment in terms of improvement from baseline was evaluated on a 3-point scale. Patients were then scheduled for follow-up visits every 12 weeks to assess long-term effectiveness. RESULTS: All 16 patients experienced an improvement in their PPR following treatment with oral azithromycin. Eight weeks after completion of treatment, 14 patients (87.5%) showed complete or almost complete recovery (slight or no residual redness and complete clearance of papules and pustules). Only 2 patients experienced a new episode of inflammatory PPR lesions during follow-up. CONCLUSIONS: The findings of this pilot study suggest that oral azithromycin could be a very effective short-term and long-term treatment for RPP resistant to conventional treatment.

Evaluación del coste económico de la técnica de la biopsia selectiva del ganglio centinela en melanoma / Cost Analysis of Sentinel Lymph Node Biopsy in Melanoma

INTRODUCCIÓN Y OBJETIVO: La técnica de la biopsia selectiva del ganglio centinela (BSGC) es la mejor herramienta para la estadificación ganglionar en el melanoma, permitiendo la realización de una linfadenectomía selectiva, es decir, reservada solo a aquellos pacientes que muestran el GC positivo para metástasis. Nuestro objetivo fue evaluar el coste económico de la técnica de la BSGC, ya que se ha convertido en el procedimiento recomendado como estándar en la atención al paciente con melanoma, y es necesaria para la inclusión de los pacientes en los ensayos clínicos. Existe además escasa bibliografía en nuestro medio sobre su relevancia económica. MÉTODO: De forma prospectiva se recogieron 100 pacientes a los que se realizó la técnica entre los años 2007-2010 con un procesamiento histológico transhiliar bivalvo multisecciones. Realizamos un cálculo aproximado del precio de la técnica utilizando las tarifas de precios oficiales de la Región de Murcia. RESULTADOS: El porcentaje de positividad de nuestra serie fue del 20%, con un número medio de ganglios de 1,96 y un 44% de melanomas delgados. El precio total de la técnica es de 9.486,57- 10.471,29 euros, siendo una parte muy importante de la misma atribuible al procesamiento histopatológico (5.769,36 euros). DISCUSIÓN: La técnica de la BSGC tiene un precio muy considerable, aunque en consonancia con otras referencias americanas previamente descritas. La optimización de la técnica vendrá dada en función de la selección cada vez más adecuada de los pacientes que deben someterse a ella, y a la estandarización de un modelo histopatológico sensible en la detección, pero a la vez sencillo en el procesamiento

INTRODUCTION AND OBJECTIVE: Sentinel lymph node biopsy (SLNB) is the most useful tool for node staging in melanoma. SLNB facilitates selective dissection of lymph nodes, that is, the performance of lymphadenectomy only in patients with sentinel nodes positive for metastasis. Our aim was to assess the cost of SLNB, given that this procedure has become the standard of care for patients with melanoma and must be performed whenever patients are to be enrolled in clinical trials. Furthermore, the literature on the economic impact of SLNB in Spain is scarce. METHOD: From 2007 to 2010, we prospectively collected data for 100 patients undergoing SLNB followed by transhilar bivalving and multiple-level sectioning of the node for histology. Our estimation of the cost of the technique was based on official pricing and fee schedules for the Spanish region of Murcia. RESULTS: The rate of node-positive cases in our series was 20%, and the mean number of nodes biopsied was 1.96; 44% of the patients in the series had thin melanomas. The total cost was estimated at between D 9486.57 and D 10 471.29. Histopathology accounted for a considerable portion of the cost (D 5769.36). DISCUSSION: The cost of SLNB is high, consistent with amounts described for a US setting. Optimaluse of SLNB will come with the increasingly appropriate selection of patients who should undergo the procedure and the standardization of a protocol for histopathologic evaluation that is both sensitive and easy to perform

Cost analysis of sentinel lymph node biopsy in melanoma.

INTRODUCTION AND OBJECTIVE: Sentinel lymph node biopsy (SLNB) is the most useful tool for node staging in melanoma. SLNB facilitates selective dissection of lymph nodes, that is, the performance of lymphadenectomy only in patients with sentinel nodes positive for metastasis. Our aim was to assess the cost of SLNB, given that this procedure has become the standard of care for patients with melanoma and must be performed whenever patients are to be enrolled in clinical trials. Furthermore, the literature on the economic impact of SLNB in Spain is scarce. METHOD: From 2007 to 2010, we prospectively collected data for 100 patients undergoing SLNB followed by transhilar bivalving and multiple-level sectioning of the node for histology. Our estimation of the cost of the technique was based on official pricing and fee schedules for the Spanish region of Murcia. RESULTS: The rate of node-positive cases in our series was 20%, and the mean number of nodes biopsied was 1.96; 44% of the patients in the series had thin melanomas. The total cost was estimated at between €9486.57 and €10471.29. Histopathology accounted for a considerable portion of the cost (€5769.36). DISCUSSION: The cost of SLNB is high, consistent with amounts described for a US setting. Optimal use of SLNB will come with the increasingly appropriate selection of patients who should undergo the procedure and the standardization of a protocol for histopathologic evaluation that is both sensitive and easy to perform.

Utilidad de la tinción con laminina-332 para diferenciar queratoacantoma, queratoacantoma con áreas de carcinoma epidermoide y carcinoma epidermoide crateriforme / The Value of Laminin-322 Staining in Distinguishing Between Keratoacanthoma, Keratoacanthoma With Areas of Squamous Cell Carcinoma, and Crateriform Squamous Cell Carcinoma

Introducción: El queratoacantoma (QA) es un tumor cutáneo crateriforme, de crecimiento rápido; aproximadamente el 25% de los QA presentan transformación maligna (QAm), observándose áreas de carcinoma epidermoide (CE). La laminina-332 se ha relacionado con progresión a fases invasoras en diversos CE. El objetivo de este estudio es evaluar si la tinción con laminina-332 es útil para distinguir QA, QAm y CE. Material y métodos: Seleccionamos 74 casos del archivo de Anatomía Patológica. Se analizaron 4 grupos: 20 QA sin CE, 20 QAm con áreas evidentes de CE, 20 CE invasores sin relación con QA (8 con morfología crateriforme) y 14 casos «problema» (QA con «dudosas» áreas de CE). Posteriormente se realizó tinción inmunohistoquímica para laminina-332 a todas estas lesiones. Resultados: En las áreas de CE asociado a QAm y en los CE invasores, la tinción con laminina fue positiva de forma intensa, habitualmente en el frente invasor del CE, a diferencia de los QA, en que la tinción fue positiva solo de forma débil y focal, en células aisladas o en pequeños «grupos» celulares. Los casos «problema» se reexaminaron tras valorar la tinción con laminina-332 (8 se diagnosticaron de QA con CE incipiente, 6 de QA sin CE). Conclusiones: La tinción con laminina-332 es diferente en los QA respecto a los CE, por lo que ayudaría a diferenciar los QA de los CE invasores y de las áreas de CE en QAm, así como en el diagnóstico de QA con «dudosas» áreas de CE y QA con CE incipientes (AU)

Introduction: Keratoacanthoma is a fast-growing crateriform skin tumor. Approximately 25% of such tumors undergo malignant transformation and develop areas of squamous cell carcinoma (SCC). The presence of laminin-322 has been associated with progression to invasive forms of SCC. The aim of this study was to determine whether or not immunohistochemical staining for laminin-322 would be of value in distinguishing between keratoacanthomas, keratoacanthomas with areas of squamous cell carcinoma, and SCCs. Material and methods: Seventy-four lesions were selected from the pathology archives of our hospital and divided into 4 groups: 20 keratoacanthomas without SCC, 20 keratoacanthomas with areas of squamous cell carcinoma, 20 invasive SCCs (8 with crateriform morphology) unrelated to keratoacanthoma, and 14 problem lesions (keratoacanthomas with areas suggestive of SCC). All 74 lesions were stained for laminin-322. Results: Laminin-322 staining was strongly positive both in areas of SCC in keratoacanthomas with malignant transformation and in invasive SCCs (mostly at the invasive front of the SCC). However, in benign keratoacanthomas, it was only weakly positive and furthermore it was confined to isolated cells or small groups of cells. The 14 problem lesions were reexamined after laminin-322 staining and 8 were diagnosed as keratoacanthomas with incipient SCC and 6 as keratoacanthomas without SCC. Conclusions: Laminin-322 staining is different in keratoacanthomas and SCCs and would thus be a useful test for differentiating keratoacanthomas from both invasive SCCs and keratoacanthomas with areas of squamous cell carcinoma. It would also be of value in diagnosing keratoacanthomas with areas suggestive of SCC or with incipient SCC (AU)

[The value of laminin-322 staining in distinguishing between keratoacanthoma, keratoacanthoma with areas of squamous cell carcinoma, and crateriform squamous cell carcinoma]. / Utilidad de la tinción con laminina-332 para diferenciar queratoacantoma, queratoacantoma con áreas de carcinoma epidermoide y carcinoma epidermoide crateriforme.

INTRODUCTION: Keratoacanthoma is a fast-growing crateriform skin tumor. Approximately 25% of such tumors undergo malignant transformation and develop areas of squamous cell carcinoma (SCC). The presence of laminin-322 has been associated with progression to invasive forms of SCC. The aim of this study was to determine whether or not immunohistochemical staining for laminin-322 would be of value in distinguishing between keratoacanthomas, keratoacanthomas with areas of squamous cell carcinoma, and SCCs. MATERIAL AND METHODS: Seventy-four lesions were selected from the pathology archives of our hospital and divided into 4 groups: 20 keratoacanthomas without SCC, 20 keratoacanthomas with areas of squamous cell carcinoma, 20 invasive SCCs (8 with crateriform morphology) unrelated to keratoacanthoma, and 14 problem lesions (keratoacanthomas with areas suggestive of SCC). All 74 lesions were stained for laminin-322. RESULTS: Laminin-322 staining was strongly positive both in areas of SCC in keratoacanthomas with malignant transformation and in invasive SCCs (mostly at the invasive front of the SCC). However, in benign keratoacanthomas, it was only weakly positive and furthermore it was confined to isolated cells or small groups of cells. The 14 problem lesions were reexamined after laminin-322 staining and 8 were diagnosed as keratoacanthomas with incipient SCC and 6 as keratoacanthomas without SCC. CONCLUSIONS: Laminin-322 staining is different in keratoacanthomas and SCCs and would thus be a useful test for differentiating keratoacanthomas from both invasive SCCs and keratoacanthomas with areas of squamous cell carcinoma. It would also be of value in diagnosing keratoacanthomas with areas suggestive of SCC or with incipient SCC.

Tinción inmunohistoquímica p16 en carcinomas epidermoides del área genital y extragenital / Immunohistochemical Staining of p16 in Squamous Cell Carcinomas of the Genital and Extragenital Area

Introducción: La proteína p16 es una proteína supresora tumoral. El objetivo del estudio era comprobar si la tinción p16 se relaciona con la presencia de papilomavirus (subtipos mucosos o α, VPH-mc) en carcinomas epidermoides (CE) extragenitales (como ocurre en el cérvix y en CE genitales). Material y método: Se realizó tinción inmunohistoquímica con p16 a diversas lesiones incluidas en parafina del área genital (8 condilomas, tres CE intraepidérmicos y 7 CE invasores) y del área extragenital (20 CE intraepidérmicos tipo enfermedad de Bowen [EB] y 10 CE invasores). La detección de VPH-mc se realizó mediante reacción en cadena de la polimerasa (PCR). Resultados: En el área genital la tinción p16 fue negativa en los condilomas y positiva en los tres CE intraepidérmicos y en dos CE invasores (29%). Se detectó VPH-mc en 6 condilomas y dos CE intraepidérmicos (100%, excluyendo tres lesiones que no se pudieron estudiar con PCR) y en los dos CE invasores positivos para p16. En el área extragenital la tinción p16 fue positiva en 19 EB (95%) y en dos CE invasores (20%). Se detectó VPH-mc en 4 EB (tinción p16 positiva) y en un CE invasor (p16 negativa). En los CE intraepidérmicos la tinción p16 fue útil para objetivar si existían focos de microinfiltración dérmica o invasión de estructuras anexiales normales. Conclusiones: Según nuestros resultados la positividad de p16 es independiente de la detección de VPH en los CE extragenitales, al contrario de lo observado en CE genitales. En el área extragenital la pérdida de proteína p16 en los CE invasores respecto a los CE intraepidérmicos indicaría progresión tumoral (AU)

Background and objectives: Positive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or alfa subtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC. Material and methods: Paraffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR). Results: In the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages. Conclusions: According to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease (AU)

[Immunohistochemical staining of p16 in squamous cell carcinomas of the genital and extragenital area]. / Tinción inmunohistoquímica p16 en carcinomas epidermoides del área genital y extragenital.

BACKGROUND AND OBJECTIVES: Positive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or αsubtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC. MATERIAL AND METHODS: Paraffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR). RESULTS: In the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages. CONCLUSIONS: According to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease.

¿Se puede mitigar el dolor asociado a las verrugas plantares? / Relieving the Pain Associated with Plantar Warts

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[Solar elastosis in cutaneous squamous cell carcinoma]. / Elastosis solar en carcinomas espinocelulares cutáneos.

INTRODUCTION: Solar elastosis, or basophilic degeneration of collagen, may be a histologic sign of chronic sun damage. MATERIAL AND METHODS: We reviewed 222 cases of squamous cell carcinoma (SCC) to identify the presence of solar elastosis and its possible invasion of the upper, middle, or deep reticular dermis. We also analyzed clinical variables such as SCC location, location in exposed areas of the skin, age, sex, and immunosuppression. Patients included had undergone surgical excision of an SCC. RESULTS: Severe solar elastosis was found in most cases (182 patients, 82%): 87 extended to the middle reticular dermis and 95 had reached the deep reticular dermis. Only 6 (2.7%) patients had no solar elastosis. In some cases elastosis was so severe that it had affected the subcutaneous cellular tissue or venous or arteriolar walls. Deeper solar elastosis was significantly associated with older age and female sex. CONCLUSIONS: Solar elastosis was found in most patients with SCC and seems to indicate chronic severe solar damage. Exposure to ultraviolet radiation would be the main cause of SCC, although other factors might also be implicated, particularly in patients who did not have severe solar elastosis. Systemic or localized immunosuppression was associated with nearly all the SCC cases studied, consistent with the marked immunosuppressant effects of sun exposure, the aging process, or both.

Elastosis solar en carcinomas espinocelulares cutáneos / Solar Elastosis in Cutaneous Squamous Cell Carcinoma

Introducción: El hallazgo de elastosis solar (degeneración basófila del colágeno) se podría considerar como un signo histológico del daño solar crónico. Material y método: Se ha realizado un estudio retrospectivo sobre 222 carcinomas espinocelulares (CE). Se ha valorado si existía elastosis solar y si esta se extendía hasta la dermis reticular superficial, media o profunda. También se han analizado otras variables clínicas como la localización, la ubuicación en áreas fotoexpuestas, así como la edad, el sexo y la inmunodepresión de los pacientes a los que se extirparon estos CE. Resultados: En la mayoría de CE (182CE, un 82%) se observa una intensa elastosis solar: 87CE presentaban elastosis solar hasta la dermis reticular media y 95CE hasta la dermis reticular profunda. Sólo hubo 6CE (2,7%) que no presentaban elastosis solar. En algunos CE la elastosis solar era tan intensa que se extendía hasta el tejido celular subcutáneo o afectaba a la pared de venas y/o arteriolas. Existía una relación significativa entre la observación de elastosis solar a más profundidad y una edad mayor, así como con el sexo femenino. Conclusiones: En la mayoría de CE se observa elastosis solar, lo que podría traducir un intenso daño solar crónico. La radiación ultravioleta sería el principal factor etiopatogénico en la mayoría de CE, aunque también podrían estar implicados otros factores etiopatogénicos, sobre todo en aquellos CE sin una elastosis solar intensa. Casi todos estos CE estudiados se asociarían a inmunodepresión (sistémica o localizada), basándonos en los importantes efectos inmunosupresores que producen las radiaciones solares, la edad avanzada o ambas (AU)

Introduction: Solar elastosis, or basophilic degeneration of collagen, may be a histologic sign of chronic sun damage. Material and methods: We reviewed 222 cases of squamous cell carcinoma (SCC) to identify the presence of solar elastosis and its possible invasion of the upper, middle, or deep reticular dermis. We also analyzed clinical variables such as SCC location, location in exposed areas of the skin, age, sex, and immunosuppression. Patients included had undergone surgical excision of an SCC. Results: Severe solar elastosis was found in most cases (182 patients, 82%): 87 extended to the middle reticular dermis and 95 had reached the deep reticular dermis. Only 6 (2.7%) patients had no solar elastosis. In some cases elastosis was so severe that it had affected the subcutaneous cellular tissue or venous or arteriolar walls. Deeper solar elastosis was significantly associated with older age and female sex. Conclusions: Solar elastosis was found in most patients with SCC and seems to indicate chronic severe solar damage. Exposure to ultraviolet radiation would be the main cause of SCC, although other factors might also be implicated, particularly in patients who did not have severe solar elastosis. Systemic or localized immunosuppression was associated with nearly all the SCC cases studied, consistent with the marked immunosuppressant effects of sun exposure, the aging process, or both (AU)

Utilidad de la tinción inmunohistoquímica con CD34 en el diagnóstico de lesiones con diferenciación tricolemal / Utility of Immunohistochemical Analysis of CD34 Expression in the Diagnosis of Lesions With Trichilemmal Differentiation

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Lesión pigmentada plantar asintomática en una mujer joven / Asymptomatic Pigmented Lesion on the Sole of a Young Woman

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[Clear cells in cutaneous squamous cell carcinoma]. / Las células claras en el carcinoma espinocelular cutáneo.

INTRODUCTION: Although few cases of squamous cell carcinoma (SCC) with clear cells have been published, we believe that these cells are often present in SCC. MATERIAL AND METHODS: We studied 249 SCCs, analyzing a number of clinical and histological variables. Various immunohistochemical techniques (immunoperoxidase method) were used to determine whether adnexal differentiation was present. RESULTS: There were 96 SCCs with a proportion of clear cells of over 25 %. Advanced or established SCCs and SCCs associated with Bowen disease contained a larger proportion of clear cells. We defined 2 histological patterns: a) clear cells around the keratin pearls of SCCs arising from pre-existing actinic keratosis and with indirect signs of human papilloma virus infection in hair follicles; and b) clear cells that simulate adnexal differentiation in lesions arising on pre-existing Bowen disease lesions. There were also 19 carcinomas with true adnexal differentiation. DISCUSSION: Clear cells are frequently observed in SCC, though large numbers of clear cells are present only in certain SCCs. The appearance of clear cells in SCCs is progressive and they are only present in more advanced SCC. The presence of clear cells is suggestive of adnexal differentiation; however, in the majority of cases, their presence is due to infiltration of normal adnexal structures by the cells of pagetoid Bowen disease. True adnexal differentiation exists only in a small percentage of cases (7.6 % in our study). The histological pattern described as clear cells around keratin pearls practically rules out this differentiation.