Melanoma sobre nevus azul en placa o sobre melanocitosis dérmicas: utilidad diagnóstica y pronóstica del BAP1 / Melanoma arising in plaque-type blue nevus and dermal melanocytosis: Diagnostic and prognostic value of BAP1

El melanoma sobre nevus azul o melanoma ex-blue nevus es una variedad de melanoma peculiar que tiene un perfil genético diferente al del resto de los melanomas cutáneos y sorprendentemente superponible al perfil del melanoma uveal. Aunque puede aparecer de novo, el melanoma ex-blue nevus se suele desarrollar sobre un nevus azul previo o sobre una melanocitosis dérmica. No todas las lesiones nodulares desarrolladas sobre un nevus azul o una melanocitosis dérmica son melanomas, y los hallazgos clínicos e histológicos pueden ser insuficientes para llegar a un diagnóstico de certeza. Así, cobran relevancia estudios adicionales, como la hibridación genómica comparada, pues la presencia de aberraciones cromosómicas favorece el diagnóstico de malignidad. Es de especial utilidad el estudio del gen BAP1, cuya pérdida de expresión orienta a melanoma en este espectro de lesiones. Presentamos 3casos del espectro nevus azul a melanoma ex-blue nevus con estudios de biología molecular (AU)

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques (AU)

[Translated article] Melanoma Arising in Plaque-Type Blue Nevus and Dermal Melanocytosis: Diagnostic and Prognostic Value of BAP1 / Melanoma sobre nevus azul en placa o sobre melanocitosis dérmicas: utilidad diagnóstica y pronóstica del BAP1

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques (AU)

El melanoma sobre nevus azul o melanoma ex-blue nevus es una variedad de melanoma peculiar que tiene un perfil genético diferente al del resto de los melanomas cutáneos y sorprendentemente superponible al perfil del melanoma uveal. Aunque puede aparecer de novo, el melanoma ex-blue nevus se suele desarrollar sobre un nevus azul previo o sobre una melanocitosis dérmica. No todas las lesiones nodulares desarrolladas sobre un nevus azul o una melanocitosis dérmica son melanomas, y los hallazgos clínicos e histológicos pueden ser insuficientes para llegar a un diagnóstico de certeza. Así, cobran relevancia estudios adicionales, como la hibridación genómica comparada, pues la presencia de aberraciones cromosómicas favorece el diagnóstico de malignidad. Es de especial utilidad el estudio del gen BAP1, cuya pérdida de expresión orienta a melanoma en este espectro de lesiones. Presentamos 3casos del espectro nevus azul a melanoma ex-blue nevus con estudios de biología molecular (AU)

Melanoma arising in plaque-type blue nevus and dermal melanocytosis: Diagnostic and prognostic value of BAP1. / Melanoma sobre nevus azul en placa o sobre melanocitosis dérmicas: utilidad diagnóstica y pronóstica del BAP1.

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques.

Prognostic Value of Vitamin D Serum Levels in Cutaneous Melanoma. / Efecto de los niveles séricos de vitamina D en el pronóstico del melanoma cutáneo.

INTRODUCTION: Vitamin D plays a fundamental role in many metabolic pathways, including those involved in cell proliferation and the immune response. Serum levels of this vitamin have been linked to melanoma risk and prognosis. This study aimed to assess the prognostic value of vitamin D serum level in melanoma. MATERIAL AND METHODS: Retrospective, observational, longitudinal, and analytical study of 286 patients with a histologic diagnosis of melanoma in whom serum levels of vitamin D were measured at the time of diagnosis. We analyzed associations between serum level and epidemiologic and clinical variables and pathology findings; we also analyzed the influence of vitamin D on overall survival. An iterative loop was used to identify a vitamin D serum level to test for its an association with survival. RESULTS: A vitamin D level less than 9.25ng/mL was associated with a histologic finding of ulceration. After a median follow-up period of 39.4 months, 24 patients (8.4%) had died. The cutoff of 9.25ng/mL was associated with lower overall survival according to both the Kaplan-Meier curves and multivariate Cox regression analysis. CONCLUSION: Vitamin D levels less than 9.25ng/mL are associated with ulceration in melanoma and serve as an independent prognostic factor for overall survival in this disease.

Efecto de los niveles séricos de vitamina D en el pronóstico del melanoma cutáneo / Prognostic Value of Vitamin D Serum Levels in Cutaneous Melanoma

Introducción: La vitamina D tiene un rol fundamental en múltiples vías metabólicas, incluidas vías implicadas en la proliferación celular y la respuesta inmune. Sus niveles han mostrado una asociación con el riesgo de desarrollar el melanoma cutáneo y su pronóstico. El objetivo de este estudio fue evaluar si los niveles séricos de vitamina D influyen en el pronóstico del melanoma. Materiales y métodos: Estudio de cohorte retrospectivo, observacional, longitudinal y analítico en 286 pacientes con diagnóstico histológico de melanoma, en los que se midieron los niveles séricos de vitamina D en el momento del diagnóstico. Se analizó la relación entre los niveles de vitamina D y las características epidemiológicas, clínicas y patológicas de los pacientes, y el efecto de la vitamina D en la supervivencia global de los pacientes. Mediante un bucle iterativo se encontró el punto de corte de los niveles séricos de vitamina D de 9,25ng/mL para su relación con la supervivencia. Resultados: Un nivel bajo de vitamina D (<9,25ng/mL) se relacionó con la ulceración en el análisis histológico. Tras una mediana de seguimiento de 39,4 meses, 24 pacientes (8,4%) fallecieron. Unos niveles de vitamina D<9,25ng/mL se asociaron con una menor supervivencia global, tanto en el análisis a través de curvas de Kaplan-Meier, como tras la regresión de Cox multivariada. Conclusión: Los niveles<9,25ng/mL de vitamina D se asocian a la presencia de ulceración histológica en el melanoma y son un factor pronóstico independiente para la supervivencia global en estos pacientes (AU)

Introduction: Vitamin D plays a fundamental role in many metabolic pathways, including those involved in cell proliferation and the immune response. Serum levels of this vitamin have been linked to melanoma risk and prognosis. This study aimed to assess the prognostic value of vitamin D serum level in melanoma. Material and methods: Retrospective, observational, longitudinal, and analytical study of 286 patients with a histologic diagnosis of melanoma in whom serum levels of vitamin D were measured at the time of diagnosis. We analyzed associations between serum level and epidemiologic and clinical variables and pathology findings; we also analyzed the influence of vitamin D on overall survival. An iterative loop was used to identify a vitamin D serum level to test for its an association with survival. Results: A vitamin D level less than 9.25ng/mL was associated with a histologic finding of ulceration. After a median follow-up period of 39.4 months, 24 patients (8.4%) had died. The cutoff of 9.25ng/mL was associated with lower overall survival according to both the Kaplan-Meier curves and multivariate Cox regression analysis. Conclusion: Vitamin D levels less than 9.25ng/mL are associated with ulceration in melanoma and serve as an independent prognostic factor for overall survival in this disease (AU)

[Translated article] Prognostic Value of Vitamin D Serum Levels in Cutaneous Melanoma / Efecto de los niveles séricos de vitamina D en el pronóstico del melanoma cutáneo

Introduction: Vitamin D plays a fundamental role in many metabolic pathways, including those involved in cell proliferation and the immune response. Serum levels of this vitamin have been linked to melanoma risk and prognosis. This study aimed to assess the prognostic value of vitamin D serum level in melanoma. Material and methods: Retrospective, observational, longitudinal, and analytical study of 286 patients with a histologic diagnosis of melanoma in whom serum levels of vitamin D were measured at the time of diagnosis. We analyzed associations between serum level and epidemiologic and clinical variables and pathology findings; we also analyzed the influence of vitamin D on overall survival. An iterative loop was used to identify a vitamin D serum level to test for its an association with survival. Results: A vitamin D level less than 9.25ng/mL was associated with a histologic finding of ulceration. After a median follow-up period of 39.4 months, 24 patients (8.4%) had died. The cutoff of 9.25ng/mL was associated with lower overall survival according to both the Kaplan-Meier curves and multivariate Cox regression analysis. Conclusion: Vitamin D levels less than 9.25ng/mL are associated with ulceration in melanoma and serve as an independent prognostic factor for overall survival in this disease (AU)

Introducción: La vitamina D tiene un rol fundamental en múltiples vías metabólicas, incluidas vías implicadas en la proliferación celular y la respuesta inmune. Sus niveles han mostrado una asociación con el riesgo de desarrollar el melanoma cutáneo y su pronóstico. El objetivo de este estudio fue evaluar si los niveles séricos de vitamina D influyen en el pronóstico del melanoma. Materiales y métodos: Estudio de cohorte retrospectivo, observacional, longitudinal y analítico en 286 pacientes con diagnóstico histológico de melanoma, en los que se midieron los niveles séricos de vitamina D en el momento del diagnóstico. Se analizó la relación entre los niveles de vitamina D y las características epidemiológicas, clínicas y patológicas de los pacientes, y el efecto de la vitamina D en la supervivencia global de los pacientes. Mediante un bucle iterativo se encontró el punto de corte de los niveles séricos de vitamina D de 9,25ng/mL para su relación con la supervivencia. Resultados: Un nivel bajo de vitamina D (<9,25ng/mL) se relacionó con la ulceración en el análisis histológico. Tras una mediana de seguimiento de 39,4 meses, 24 pacientes (8,4%) fallecieron. Unos niveles de vitamina D<9,25ng/mL se asociaron con una menor supervivencia global, tanto en el análisis a través de curvas de Kaplan-Meier, como tras la regresión de Cox multivariada. Conclusión: Los niveles<9,25ng/mL de vitamina D se asocian a la presencia de ulceración histológica en el melanoma y son un factor pronóstico independiente para la supervivencia global en estos pacientes (AU)

Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma / Protocol for the Histologic Diagnosis of Cutaneous Melanoma: Consensus Statement of the Spanish Society of Pathology and the Spanish Academy of Dermatology and Venereology (AEDV) for the National Cutaneous Melanoma Registry

El presente texto es una propuesta de protocolo de diagnóstico histológico para el melanoma cutáneo realizada a instancias del Registro Nacional de Melanoma de la Academia Española de Dermatología y Venereología. Tras una búsqueda bibliográfica, un grupo de ocho panelistas (siete patólogos) decidieron entre 36 variables del tumor primario, el ganglio centinela y la linfadenectomía incluir un total de 30 variables mediante el método de Delphi modificado. Se han consensuado las variables que deberían contener un informe histológico de melanoma cutáneo para que puedan ser utilizadas en el Registro de Melanoma o servir de modelo para los distintos Servicios de Anatomía Patológica a la hora de elaborar sus propios informes de forma rutinaria

This article describes a proposed protocol for the histologic diagnosis of cutaneous melanoma developed for the National Cutaneous Melanoma Registry managed by the Spanish Academy of Dermatology and Venereology (AEDV). Following a review of the literature, 36 variables relating to primary tumors, sentinel lymph nodes, and lymph node dissection were evaluated using the modified Delphi method by a panel of 8 specialists (including 7 pathologists). Consensus was reached on the 30 variables that should be included in all pathology reports for cutaneous melanoma and submitted to the Melanoma Registry. This list can also serve as a model to guide routine reporting in pathology departments

Protocol for the Histologic Diagnosis of Cutaneous Melanoma: Consensus Statement of the Spanish Society of Pathology and the Spanish Academy of Dermatology and Venereology (AEDV) for the National Cutaneous Melanoma Registry. / Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma.

This article describes a proposed protocol for the histologic diagnosis of cutaneous melanoma developed for the National Cutaneous Melanoma Registry managed by the Spanish Academy of Dermatology and Venereology (AEDV). Following a review of the literature, 36 variables relating to primary tumors, sentinel lymph nodes, and lymph node dissection were evaluated using the modified Delphi method by a panel of 8 specialists (including 7 pathologists). Consensus was reached on the 30 variables that should be included in all pathology reports for cutaneous melanoma and submitted to the Melanoma Registry. This list can also serve as a model to guide routine reporting in pathology departments.

Clinical, environmental and histological distribution of BRAF, NRAS and TERT promoter mutations among patients with cutaneous melanoma: a retrospective study of 563 patients.

BACKGROUND: The distinct somatic mutations that define clinical and histopathological heterogeneity in cutaneous melanoma could be dependent on host susceptibility to exogenous factors like ultraviolet radiation. OBJECTIVES: Firstly, to characterize patients with cutaneous melanoma clinically and pathologically based on the mutational status of BRAF, NRAS and TERT promoter. Secondly, to elucidate the modified features due to the presence of TERT promoter mutations over the background of either BRAF or NRAS mutations. METHODS: We performed a retrospective study on 563 patients with melanoma by investigating somatic mutations in BRAF, NRAS and TERT promoter. RESULTS: We observed co-occurrence of TERT promoter mutations with BRAF and NRAS mutations in 26.3% and 6.9% of melanomas, respectively. Multivariate analysis showed an independent association between BRAF mutations and a decreased presence of cutaneous lentigines at the melanoma site, and an increased association with the presence of any MC1R polymorphism. We also observed an independent association between TERT promoter mutations and increased tumour mitotic rate. Co-occurrence of BRAF and TERT promoter mutations was independently associated with occurrence of primary tumours at usually sun-exposed sites, lack of histological chronic sun damage in surrounding unaffected skin at the melanoma site, and increased tumour mitotic rate. Co-occurrence of NRAS and TERT promoter mutations was independently associated with increased tumour mitotic rate. The presence of TERT promoter together with BRAF or NRAS mutations was associated with statistically significantly worse survival. CONCLUSIONS: The presence of TERT promoter mutations discriminates BRAF- and NRAS-mutated tumours and indicates a higher involvement of ultraviolet-induced damage and tumours with worse melanoma-specific survival than those without any mutation. These observations refine classification of patients with melanoma based on mutational status.

Cirugía por etapas con control micrográfico de los márgenes del lentigo maligno / Staged Excision With Micrographic Monitoring of Margins in Lentigo Maligna

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Risk factors for the development of a second melanoma in patients with cutaneous melanoma.

BACKGROUND: Cutaneous melanoma patients have an increased risk of developing other neoplasms, especially cutaneous neoplasms and other melanomas. Identifying factors associated with an increased risk might be useful in the development of melanoma guidelines. OBJECTIVES: To identify risk factors related to the development of a second primary melanoma in a series of patients diagnosed with sporadic melanoma and to establish the estimated incidence rate. METHODS: A longitudinal study based on prospective follow-up information of patients diagnosed with sporadic cutaneous melanoma at our centre from 2000 to 2015 was performed. Cumulative incidence was estimated based on competing risk models, and the association of characteristics with the risk of a second melanoma was performed by Cox proportional hazard models. RESULTS: Out of 1447 patients included in the study, after a median follow-up of 61 months, 55 patients (3.8%) developed a second melanoma. Fair hair colour, more than 100 common melanocytic nevi and the presence of more than 50 cherry angiomas were independently associated with the development of a second melanoma. The site and the histological subtype of the first and second melanomas were not consistent. The second melanomas were thinner than the first ones. CONCLUSIONS: Fair-haired and multiple-nevi patients might benefit from more intensive prevention measures. The finding of cherry angiomas as a risk factor suggests that these lesions could be markers of skin sun damage in the setting of certain degree of genetic susceptibility.

Histologic Changes During Treatment With Vismodegib in Locally Advanced Basal Cell Carcinoma: A Series of 19 Cases.

BACKGROUND: There are no large series describing cutaneous histologic changes during treatment with vismodegib in locally advanced basal cell carcinoma (BCC). OBJECTIVE: To analyze histologic changes in skin biopsy specimens from patients with locally advanced BCC treated with vismodegib. METHODS: A descriptive, retrospective study of patients with locally advanced BCC treated with vismodegib between June 2012 and December 2017 at the Instituto Valenciano de Oncología, Spain. Nineteen patients were biopsied before and during the treatment with vismodegib, and we compared histologic changes observed. RESULTS: Seven patients (37%) achieved complete response, which was characterized by replacement of tumor stroma with a hyaline scar, lymphocytic inflammatory infiltrate, keratin formation, and infundibular cysts. Twelve patients (63%) achieved partial response; 5 showed no phenotypic changes, whereas 7 showed histologic changes; 5 cases showed metatypical differentiation; and 2 cases presented squamous differentiation. We observed no cases of squamous cell carcinoma arising at vismodegib treatment sites and no association between initial histologic subtype and clinical response. LIMITATIONS: Many biopsy specimens were obtained by punch biopsy and may not be representative of the full tumors. We studied histologic changes only in complete and partial responses. CONCLUSION: Vismodegib can induce histologic changes toward metatypical or squamous differentiation of BCC in patients with partial response. Keratinizing phenomena were frequent, both in partial and complete response groups.

No association between smoking and sentinel lymph node metastasis and survival in cutaneous melanoma.

BACKGROUND: There is little evidence that smoking is associated with metastasis in patients with cutaneous melanoma. OBJECTIVE: Using a propensity score matching analysis, we assessed whether smoking was associated with a higher rate of sentinel lymph node (SLN) metastasis and worse survival in these patients. METHODS: Retrospective cohort study at a referral hospital for melanoma. We studied 762 patients with known smoking status from the melanoma database of the Instituto Valenciano de Oncología who underwent SLN biopsy between 1 January 2000 and 31 December 2016. The patients were matched by smoking status. The matching procedure was implemented using three logistic regression models featuring never vs. former smokers, never vs. current smokers and former vs. current smokers. The study outcomes were disease-free survival (DFS), melanoma-specific survival (MSS), overall survival (OS) and SLN status. RESULTS: The following groups were formed based on the propensity matching scores: 114 pairs of smokers vs. never smokers, 113 pairs of smokers vs. former smokers and 174 pairs of never smokers vs. former smokers. Smoking status was not associated with SLN metastasis or with DFS, MSS or OS in any of the three groups. CONCLUSION: Smoking does not influence SLN metastasis or survival in patients with cutaneous melanoma.

Guidelines for Diagnosis and Treatment of Cutaneous Sarcomas: Dermatofibrosarcoma Protuberans. / Sarcomas cutáneos: directrices para el diagnóstico y tratamiento. Dermatofibrosarcoma protuberans.

Sarcomas comprise a broad group of tumors, many of whose biological behavior and aggressiveness differ from one type to another. The therapeutic approach is generally multidisciplinary and often complex. Developments in surgical and oncological dermatology during the last few decades have positioned dermatologists as specialists in the diagnosis and treatment of skin cancer. The aim of this article is to review the main soft tissue sarcomas that typically affect the skin. Dermatofibrosarcoma protuberans is a low-grade malignant sarcoma. It exhibits slow-growth, is locally invasive, and has low metastatic potential (<3%). Mohs micrographic surgery is the treatment of choice. The COL1A1-PDGFB translocation should be analyzed in cases of unclear diagnosis and when it is necessary to identify candidates for tyrosine kinase inhibitors. Imatinib is indicated for the treatment of locally advanced and metastatic dermatofibrosarcoma protuberans.

Experiencia con vismodegib en carcinoma basocelular avanzado en un centro oncológico / Experience With Vismodegib in the Treatment of Advanced Basal Cell Carcinoma at a Cancer Center

INTRODUCCIÓN Y OBJETIVOS: Vismodegib es el primer inhibidor selectivo de la vía de la señalización Hedgehog aprobado para el tratamiento del carcinoma basocelular (CBC) localmente avanzado y metastásico. Describimos nuestra experiencia en un centro oncológico con el vismodegib en el tratamiento de pacientes con CBC avanzados y/o múltiples durante un periodo de 5 años. MATERIAL Y MÉTODOS: Analizamos variables como la edad y el sexo del paciente, la localización, el tamaño, el tipo y las características del tumor, el tiempo de evolución, si son tumores primarios o recidivas, la duración del tratamiento, la respuesta a este (completa, parcial, estabilización o ausencia de respuesta), los efectos secundarios observados y las recidivas. RESULTADOS: Un total de 22 pacientes fueron tratados, 20 con CBC localmente avanzados y 2 con CBC metastásicos con afectación ganglionar. El tratamiento fue administrado durante 11,8 meses de media. El 41% (9) de los pacientes obtuvieron una respuesta completa al tratamiento, un 45% (10) respuesta parcial y en el 14% (3) de los pacientes el tratamiento consiguió estabilizar la enfermedad. Tras una mediana de 21 meses, 2 casos recidivaron. Los principales efectos secundarios observados fueron disgeusia, alopecia y calambres musculares, todos ellos de carácter leve. Ningún paciente desarrolló un carcinoma epidermoide sobre el área tratada con vismodegib, aunque sí cambios metatípicos tras el tratamiento. CONCLUSIONES: El vismodegib es un fármaco seguro y eficaz para el tratamiento del CBC localmente avanzado, con un porcentaje de respuesta del 86%. Los efectos adversos deben tenerse en cuenta por su alta frecuencia, aunque estos suelen ser de carácter leve

INTRODUCTION AND OBJECTIVES: Vismodegib is the first selective Hedgehog inhibitor approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). In this article, we describe our experience with the use of this drug to treat advanced and/or multiple BCCs at a cancer center over 5 years. MATERIAL AND METHODS: We analyzed the following variables: patient age and sex; tumor location, size, type, and characteristics; time since onset; primary or recurrent status; duration of treatment; response to treatment (complete, partial, stabilization, or absence of response); adverse effects; and recurrences. RESULTS: We treated 22 patients, of whom 20 had locally advanced BCCs and 2 had metastatic BCCs with lymph node involvement. The treatment was administered over a mean of 11.8 months. Nine patients (41%) achieved complete response and 10 (45%) partial response. The disease was stabilized in 3 (14%). Two patients relapsed after a median of 21 months. The main adverse effects were dysgeusia, alopecia, and muscle cramps, all of which were mild. None of the patients developed squamous cell carcinoma in an area treated with vismodegib, although metatypical changes were observed after treatment. CONCLUSIONS: With a response rate of 96%, vismodegib is a safe and effective treatment for locally advanced BCC. Adverse effects are generally mild but they need to be taken into account owing to their high frequency

Experience With Vismodegib in the Treatment of Advanced Basal Cell Carcinoma at a Cancer Center. / Experiencia con vismodegib en carcinoma basocelular avanzado en un centro oncológico.

INTRODUCTION AND OBJECTIVES: Vismodegib is the first selective Hedgehog inhibitor approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). In this article, we describe our experience with the use of this drug to treat advanced and/or multiple BCCs at a cancer center over 5 years. MATERIAL AND METHODS: We analyzed the following variables: patient age and sex; tumor location, size, type, and characteristics; time since onset; primary or recurrent status; duration of treatment; response to treatment (complete, partial, stabilization, or absence of response); adverse effects; and recurrences. RESULTS: We treated 22 patients, of whom 20 had locally advanced BCCs and 2 had metastatic BCCs with lymph node involvement. The treatment was administered over a mean of 11.8 months. Nine patients (41%) achieved complete response and 10 (45%) partial response. The disease was stabilized in 3 (14%). Two patients relapsed after a median of 21 months. The main adverse effects were dysgeusia, alopecia, and muscle cramps, all of which were mild. None of the patients developed squamous cell carcinoma in an area treated with vismodegib, although metatypical changes were observed after treatment. CONCLUSIONS: With a response rate of 96%, vismodegib is a safe and effective treatment for locally advanced BCC. Adverse effects are generally mild but they need to be taken into account owing to their high frequency.