Real-World Experience with Vismodegib on Advanced and Multiple BCCs: Data from the RELIVIS Study.

BACKGROUND: Vismodegib is approved for advanced cases of basal cell carcinomas not amenable to surgery or radiotherapy. Large studies on the use of vismodegib in clinical practice are scarce. OBJECTIVES: The main objective of the study was to analyse the evolution and therapeutic management of relapses and lack of response in patients who had received vismodegib for locally advanced and/or multiple basal cell carcinomas in a real-life multicentre setting. METHODS: This nationwide retrospective study collected data on patients treated with vismodegib in 15 specialized centres. We included patients who first received vismodegib until intolerable toxicity, maximum response, or progressive disease. Exploratory research variables referred to patient and tumour characteristics, vismodegib effectiveness and safety, relapse rate and management, and mortality. A multivariable logistic regression model was used to identify predictors of complete clinical response. RESULTS: 133 patients with advanced BCC were included in the registry. The objective response rate (ORR) was 77.5% and nearly half of the patients (45.9%) achieved complete remission. Long-term information and detailed information of subsequent treatments after a regime of vismodegib was available for 115 patients. Only 34% of the patients in this group were subsequently treated with other therapies or vismodegib rechallenge. Sixty-nine percent of the patients who had shown a complete remission with vismodegib remained free of recurrence while 30.7% relapsed. Almost half of the patients who received additional therapies after the first course of vismodegib achieved complete tumour remission. Three and 2 out of 9 patients who were rechallenged with vismodegib achieved complete and partial responses, respectively, with an ORR of 55.5%. CONCLUSION: Our study confirms efficacy of vismodegib in routine clinical practice. The risk of recurrence after achieving complete response with vismodegib was lower than previous reports. Rechallenge with vismodegib is feasible and most patients responded to re-treatment.

Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale.

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

Complications Associated with Mohs Micrographic Surgery: Data from the Nationwide Prospective Cohort REGESMOHS.

BACKGROUND: Large prospective studies on the safety of Mohs micrographic (MMS) surgery are scarce, and most focus on a single type of surgical adverse event. Mid-term scar alterations and functional loss have not been described. OBJECTIVES: To describe the risk of MMS complications and the risk factors for them. METHODS: A nationwide prospective cohort collected all adverse events on consecutive patients in 22 specialised centres. We used multilevel mixed-effects logistic regression to find out factors associated with adverse events. RESULTS: 5,017 patients were included, with 14,421 patient-years of follow-up. 7.0% had some perioperative morbidity and 6.5% had mid-term and scar-related complications. The overall risk of complications was mainly associated with use of antiaggregant/anticoagulant and larger tumours, affecting deeper structures, not reaching a tumour-free border, and requiring complex repair. Age and outpatient setting were not linked to the incidence of adverse events. Risk factors for haemorrhage (0.9%) were therapy with antiaggregant/anticoagulants, tumour size, duration of surgery, and unfinished surgery. Wound necrosis (1.9%) and dehiscence (1.0%) were associated with larger defects and complex closures. Immunosuppression was only associated with an increased risk of necrosis. Surgeries reaching deeper structures, larger tumours and previous surgical treatments were associated with wound infection (0.9%). Aesthetic scar alterations (5.4%) were more common in younger patients, with larger tumours, in H-area, and in flap and complex closures. Risk factors for functional scar alterations (1.7%) were the need for general anaesthesia, larger tumours that had received previous surgery, and flaps or complex closures. CONCLUSIONS: MMS shows a low risk of complications. Most of the risk factors for complications were related to tumour size and depth, and the resulting need for complex surgery. Antiaggregant/anticoagulant intake was associated with a small increase in the risk of haemorrhage, that probably does not justify withdrawal. Age and outpatient setting were not linked to the risk of adverse events.

Risk Factors and Rate of Recurrence after Mohs Surgery in Basal Cell and Squamous Cell Carcinomas: A Nationwide Prospective Cohort (REGESMOHS, Spanish Registry of Mohs Surgery).

Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.

Mohs micrographic surgery in dermatofibrosarcoma protuberans: Rate and risk factors for recurrence in a prospective cohort study from the Spanish Registry of Mohs Surgery (REGESMOHS) and review of the literature.

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.

State of the art of Mohs surgery for rare cutaneous tumors in the Spanish Registry of Mohs Surgery (REGESMOHS).

BACKGROUND: The use of Mohs micrographic surgery (MMS) for rare cutaneous tumors is poorly defined. We aim to describe the demographics, tumor presentation and topography, surgery characteristics and complications of MMS for rare cutaneous tumors in a national registry. METHODS: Prospective cohort study of patients treated with MMS in Spain between July 2013 and June 2018. The inclusion criteria were patients with cutaneous tumors with final diagnosis different from basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, or any kind of melanoma. RESULTS: Five thousand and ninety patients were recorded in the registry, from which only 73 tumors (1.4%) fulfilled the inclusion criteria: atypical fibroxanthoma (18), microcystic adnexal carcinoma (10), extramammary Paget's disease (7), Merkel cell carcinoma (5), dermatofibroma (4), trichilemmal carcinoma (4), desmoplastic trichoepithelioma (4), sebaceous carcinoma (3), leiomyosarcoma (2), porocarcinoma (2), angiosarcoma (2), trichoblastoma (1), superficial acral fibromyxoma (1), and others (10). No intra-surgery morbidity was registered. Postsurgery complications appeared in six patients (9%) and were considered mild. Median follow-up time was 0.9 years during which three Merkel cell carcinomas, one angiosarcoma, one microcystic adnexal carcinoma, and four others recurred (12.3%). CONCLUSION: This national registry shows that rare cutaneous tumors represent a negligible part of the total MMS performed in our country with a low complication rate.

Differences of Mohs micrographic surgery in basal cell carcinoma versus squamous cell carcinoma.

BACKGROUND: The two main tumors treated with Mohs micrographic surgery (MMS) are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There are no studies analyzing whether MMS is different when treating these two types of tumors. OBJECTIVE: We aim to compare the characteristics of the patients, the tumors, and MMS, and first-year follow-up of MMS in BCC and SCC. METHODS: REGESMOHS is a prospective cohort study of patients treated with MMS. The participating centers are 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patients, tumors, and surgery were recorded. The follow-up was done with two visits: the first visit within 1 month after surgery and the second one within the first year. RESULTS: From July 2013 to April 2017, a total of 2,669 patients who underwent MMS were included in the registry. Of them, 2,448 (93%) were diagnosed with BCC, and 181 (7%) were diagnosed with SCC. Patients with SCC were older than those with BCC (median age 73 years vs. 68 years) and presented immunosuppression more frequently. The tumor size was significantly larger in the SCC group. Regarding surgery, deeper invasion was more frequent in SCC, resulting in larger defects. Despite this, SCC did not require more stages to get clear margins or more time in the operating room. Incomplete Mohs was more frequent in the SCC group (6%) than in the BCC group (2%). The incidence of perioperative complications was higher when treating SCC. There were more relapses in the first-year follow-up in the SCC group. CONCLUSION: There are significant differences when comparing MMS in BCC and SCC. Knowledge of these differences can help to prepare the patient and plan the surgery, optimizing results.

Case report: differential diagnosis between primary cutaneous apocrine adenocarcinoma versus extramammary or metastatic breast adenocarcinoma.

Cutaneous apocrine adenocarcinoma (CAA) is a rare adnexal neoplasm that histologically can mimic breast carcinoma metastatic to the skin or apocrine carcinoma arising in ectopic breast tissue. It can present with a wide range of clinical modalities and can often simulate many benign processes, which delays its diagnosis and hinders its prognosis. We describe a case of a 33-year-old man who had a short-evolution small nodule in the right axilla with local lymph node metastases. The immunohistochemical characterization was closer to that of breast adenocarcinoma than to an adnexal neoplasm. This was established as the main differential diagnosis. Diagnosis of cutaneous apocrine adenocarcinoma may be difficult and immunomarkers are not specific. The anatomical criteria and systemic investigation are mandatory to establish the correct diagnosis.

Paniculitis pancreática como forma de presentación inicial de adenocarcinoma gástrico con metástasis hepáticas / Gastric adenocarcinoma with hepatic metastases presenting as pancreatic panniculitis

El interés del caso reportado surge a raíz de la obtención de un valor de lipasa superior a 7.000 U/l en una paciente con una paniculitis en miembros inferiores de 10 meses de evolución. Se estableció el diagnóstico de paniculitis pancreática, y adenocarcinoma gástrico con metástasis hepáticas, con la peculiaridad de no encontrar afectación clínica ni radiológica del páncreas. Las paniculitis pancreáticas de origen tumoral no pancreático constituyen una rareza, y son un hecho excepcional en la literatura médica consultada. Este es el primer caso de paniculitis pancreática como signo inicial de un cáncer gástrico, con metástasis hepáticas y con mayor supervivencia reportado en la literatura, lo cual hace que su revisión clínica e histológica sea de extraordinario interés(AU)

A patient presenting with a ten month history of progressive lower limb panniculitis was found to have more than 7,000 lipase U/L. Pancreatic panniculitis and gastric adenocarcinoma with liver metastases was diagnosed, despite no clinical or radiological findings of pancreatic disease. Pancreatic panniculitis arising from a non pancreatic primary is extremely rare. To our knowledge, this is the first time pancreatic panniculitis has been reported as the presenting sign of gastric carcinoma with hepatic metastases. It is also the longest survival to be reported to date(AU)

Papular mycosis fungoides: two new cases of a recently described clinicopathological variant of early mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. In early stages of the disease many different clinicopathologic variants have been observed. Currently, a papular variant of MF which is characterized by a good prognosis has been described. OBJECTIVE AND METHODS: Because only seven cases have been reported in the literature, clinical and morphological data of this variant are not well established. We report the clinical and histopathological characteristics of two new patients with papular mycosis fungoides and review the previous cases reported in the literature. RESULTS: The two cases of this early variant of MF were characterized by the presence of papules which, unlike the papules of lymphomatoid papulosis, did not show a tendency for spontaneous resolution. Histologic examination confirmed the diagnosis of MF in all cases. Immunohistochemical staining for CD30 was negative in all two cases. Follow-up data of our two patients confirmed the non-aggressive behavior of the disease, confirming that the lesions were not manifestations of advanced MF. CONCLUSION: Papular MF is a new variant of early MF characterized by a good prognosis in the long term follow- up. Thus, it should be added to the long list of clinicopathologic subtypes of MF.

Cirugía micrográfica de Mohs del canto interno del ojo. Estudio de casos y controles / Mohs' micrographic surgery of the medial canthus of the eye. A case-control study

Introducción: los carcinomas basocelulares (CB) localizados en zonas periorificiales y de fusión embrionaria se consideran de alto riesgo. Hemos observado que de estas localizaciones, el canto interno del ojo parece tener unas características que dan lugar a un manejo especialmente complicado de los CB. Material y métodos: se seleccionaron como casos 35 carcinomas basocelulares del canto interno del ojo (CBCIO) correspondientes a 30 pacientes y como controles 34 carcinomas basocelulares de la frente, mejillas y sien (CBOL) de 31 pacientes, todos ellos intervenidos con cirugía micrográfica de Mohs. Se evaluaron mediante estudio uni y multivariado las diferencias existentes en los siguientes datos: a) clínicos del paciente: edad y sexo; b) clínicos del tumor: tratamientos previos, tamaño tumoral, tiempo de evolución; c) histología del tumor: tipo, ulceración, estructuras infiltradas; d) cirugía: número de estadios, márgenes extirpados, defecto resultante y características de la reconstrucción, y e) seguimiento: existencia o no de recidiva. Resultados: los CBCIO tenían un menor tamaño tumoral, pero con infiltración más profunda, precisaban de un mayor número de estadios y de reconstrucciones más complejas durante el procedimiento quirúrgico y recurrieron con más frecuencia que los CBOL. Estas diferencias alcanzaron significación estadística. Conclusiones: los carcinomas basocelulares del canto interno del ojo merecen una especial consideración en cuanto a su tratamiento y se debería considerar la cirugía de Mohs como el tratamiento de elección, incluso para los casos aparentemente benignos (AU)

Valoración del tratamiento de los hemangiomas infantiles ulcerados / Evaluation of the treatment of ulcerated infantile hemangiomas

La complicación más frecuente de los hemangiomas infantiles es la ulceración; aparece en un 5%-10% de los casos, se suele acompañar de dolor, en ocasiones muy intenso, y conlleva un riesgo secundario de infección, hemorragia y cicatrices. El tratamiento clásico ha consistido en medidas locales, antibióticos tópicos u orales y corticosteroides intralesionales o sistémicos. Más recientemente se ha introducido el tratamiento con láser de colorante pulsado. Hemos tratado a nueve niños con hemangiomas infantiles ulcerados, todos ellos recibieron inicialmente tratamiento convencional y cuatro recibieron además tratamiento con láser de colorante pulsado (595 nm, 1.500 µseg) tras no observarse mejoría al cabo de 4-6 semanas. Las ulceraciones de los hemangiomas que reepitelizaron tras ser tratados de forma convencional eran más superficiales y de menor tamaño que los que necesitaron ser tratados con láser; la duración media de su reepitelización fue de 6 semanas. De los cuatro hemangiomas ulcerados tratados con láser, tres reepitelizaron tras una sesión y el restante requirió tres sesiones. Se observó una mejoría del dolor en todos los casos en la primera semana tras el tratamiento. El láser de colorante pulsado es un tratamiento a considerar en los hemangiomas infantiles ulcerados, sobre todo cuando no se observe mejoría tras tratamiento convencional durante 2 semanas. (AU)

Mucinosis folicular: nuevas entidades clínico-patológicas. Estudio clínico, histológico, inmunohistoquímico e inmunogenotípico de 23 pacientes* / Follicular mucinosis: new clinicopathologic entities. Clinical, histological, immunohistochemical and immunogenotypic study of 23 patients

En el presente trabajo se realiza una revisión clínica, histológica, inmunohistoquímica e inmunogenotípica de 23 pacientes con mucinosis folicular. Se incluyeron en el trabajo pacientes con mucinosis folicular primaria (MFP) y pacientes con mucinosis folicular secundaria (MFS) a linfoma sistémico o linfoma cutáneo de células T. Se seleccionaron del archivo de histopatología las biopsias con diagnóstico de mucinosis folicular desde 1975 al año 2000 con el único criterio de mostrar degeneración mucinosa en el epitelio folicular con un infiltrado inflamatorio acompañante. En todas las biopsias se efectuaron tinciones inmunohistoquímicas con marcadores pan B, pan T, T4 y T8. En casos seleccionados se realizó detección de reordenamiento clonal del receptor T mediante PCR de cortes en parafina de las biopsias. Se encontraron seis casos de MFS (30,4% del total), todos ellos varones de una edad media de 50,4 años. El linfoma más frecuentemente asociado fue la micosis fungoide. Dieciséis casos correspondían a MFP (ocho varones y ocho mujeres; edades entre 8 y 72 años). En este grupo de pacientes se identificaron cuatro formas clínicas de presentación: MFP localizada, MFP difusa, MFP acneiforme y MFP urticarial. No existieron diferencias histológicas sustanciales entre la MFS y la MFP. Tan sólo la forma urticarial de la mucinosis folicular presentaba características histológicas diferenciales, como fueron un abundante infiltrado inflamatorio y abundantes eosinófilos. Los hallazgos inmunohistoquímicos confirman que el infiltrado inflamatorio está formado preferentemente por linfocitos T helper. Los estudios de reordenamiento demostraron tres casos de MFP con clonalidad, sin que se pudieran encontrar características diferenciales entre éstos y las formas no clonales. Pese a la clonalidad ninguno de estos tres casos evolucionó posteriormente a linfoma, lo que sostiene la teoría de las dermatosis benignas clonales, recientemente propuesta. No obstante, parece aconsejable un seguimiento prolongado de los casos de mucinosis folicular primaria con clonalidad en el estudio genético (AU)

Dermatosis pustulosa subcórnea con anticuerpos IgA antidesmocolina / Subcorneal pustular dermatosis with IgA antibodies targeting desmocollin

Describimos el caso de una paciente de 74 años con lesiones características de dermatosis pustulosa subcórnea (DPS) o enfermedad de Sneddon-Wilkinson. La inmunofluorescencia indirecta demostró la existencia de anticuerpos IgA que se depositaban a nivel intercelular en las capas altas de la epidermis, y demostramos que el antígeno reconocido por estos anticuerpos era la desmocolina 1 (proteína constituyente de la porción extracelular de los desmosomas). En los últimos años se ha definido una nueva variedad de pénfigo, el pénfigo IgA, que se presenta bajo dos formas diferentes: la DPS y la dermatosis neutrofílica intraepidérmica. Comentamos el diagnóstico diferencial clínico e histológico de nuestro caso, con especial referencia a la diferenciación entre la DPS y la psoriasis pustulosa (AU)

La proteína S-100 como marcador tumoral en pacientes con melanoma cutáneo / S-100 protein as a tumoral marker in cutaneous melanoma patients

La proteína S100 se ha utilizado como marcador tumoral en pacientes diagnosticados de melanoma en los últimos años. Los objetivos de este estudio han sido analizar el significado de la proteína S100 en el momento del diagnóstico y evaluar su uso durante el seguimiento posterior de los pacientes. Se incluyeron 156 pacientes diagnosticados de melanoma, 58 pacientes en estadio I, 62 en estadio II, 22 en estadio III, nueve en estadio IV y en cinco pacientes en estadio I/II (18 no tratados y 138 tratados previamente). Los niveles séricos se determinaron con un ensayo inmunorradiométrico. El valor de corte fue de 0,2 µg/l. En los 18 pacientes no tratados la determinación media sérica de S100 antes del tratamiento fue de 0,235 µg/l. Estos valores fueron significativamente mayores en los pacientes con melanoma nodular y los valores medios de los estadios III y IV fueron mayores que los estadios I y II. De los 79 pacientes con dos o más determinaciones durante el seguimiento clínico se ha obtenido una sensibilidad de la proteína S100 para la detección de la progresión de la enfermedad o de la recidiva del 83,3% y una especificidad del 89,5%. Concluimos que la S100 no es eficaz para diagnosticar melanomas en estadios precoces, pero que es útil como marcador tumoral en los casos de enfermedad metastásica y en la monitorización de las respuestas a los tratamientos, y podría ser útil durante el seguimiento de los pacientes para ampliar estudios complementarios en el caso de que se positivizara (AU)