Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Nodular type but not vitamin D levels increases the risk of second primary cancers in melanoma patients: An observational study of 663 patients / El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes

Background Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). Materials and methods A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan–Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. Results Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5–7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0–4.8) were included in the final model. Conclusions Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development (AU)

Antecedentes El déficit de vitamina D se asocia con un mayor riesgo de padecer varias enfermedades, incluido el cáncer. Molecularmente, esta parece tener un efecto antineoplásico. Sin embargo, el papel que juega en la patogénesis del cáncer no está bien esclarecido y hay resultados dispares en los estudios publicados. El objetivo del presente fue determinar si unos niveles de vitamina D deficientes en el momento del diagnóstico del melanoma aumentaba el riesgo de desarrollar un cáncer no cutáneo (CNC). Material y método Se diseñó un estudio retrospectivo de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022. El efecto de cada una de las variables seleccionadas en el desarrollo de un CNC durante el seguimiento tras el diagnóstico del melanoma se realizó mediante el estudio de supervivencia con el método de Kaplan-Meier y las diferencias se evaluaron con la prueba de los rangos logarítmicos. Se elaboraron modelos uni y multivariados de riesgos proporcionales de Cox para cuantificar el efecto de cada valor de las variables de estudio en el tiempo para desarrollar un CNC. Resultados De los 663 pacientes, 34 desarrollaron un CNC tras el melanoma. No hubo diferencias estadísticamente significativas entre los grupos definidos por los niveles de vitamina D (log-rank, p = 0,761). Sin embargo, una edad > 60, el estadio III/IV, y el tipo nodular se asociaron significativamente al desarrollo de un CNC. Tras el análisis multivariado, solo la edad > 60 (hazard ratio [HR] 3,4; intervalo de confianza [IC] 95% HR:1,5-7,6) y el subtipo nodular de melanoma (HR 2,2; IC 95% HR:1,0-4,8) se mantuvieron en el modelo predictivo final. Conclusiones Nuestros resultados sugieren que unos niveles de vitamina D deficientes en el diagnóstico de melanoma no se asocian a un mayor riesgo de desarrollar un CNC. Sin embargo, en una edad > 60 y el subtipo nodular sí que aumentan el riesgo de desarrollar un CNC (AU)

[Artículo traducido] El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes / Nodular Type but Not Vitamin D Levels Increases the Risk of Second Primary Cancers in Melanoma Patients: An Observational Study of 663 Patients

Antecedentes El déficit de vitamina D se asocia con un mayor riesgo de padecer varias enfermedades, incluido el cáncer. Molecularmente, esta parece tener un efecto antineoplásico. Sin embargo, el papel que juega en la patogénesis del cáncer no está bien esclarecido y hay resultados dispares en los estudios publicados. El objetivo del presente fue determinar si unos niveles de vitamina D deficientes en el momento del diagnóstico del melanoma aumentaba el riesgo de desarrollar un cáncer no cutáneo (CNC). Material y método Se diseñó un estudio retrospectivo de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022. El efecto de cada una de las variables seleccionadas en el desarrollo de un CNC durante el seguimiento tras el diagnóstico del melanoma se realizó mediante el estudio de supervivencia con el método de Kaplan-Meier y las diferencias se evaluaron con la prueba de los rangos logarítmicos. Se elaboraron modelos uni y multivariados de riesgos proporcionales de Cox para cuantificar el efecto de cada valor de las variables de estudio en el tiempo para desarrollar un CNC. Resultados De los 663 pacientes, 34 desarrollaron un CNC tras el melanoma. No hubo diferencias estadísticamente significativas entre los grupos definidos por los niveles de vitamina D (log-rank, p = 0,761). Sin embargo, una edad > 60, el estadio III/IV, y el tipo nodular se asociaron significativamente al desarrollo de un CNC. Tras el análisis multivariado, solo la edad > 60 (hazard ratio [HR] 3,4; intervalo de confianza [IC] 95% HR:1,5-7,6) y el subtipo nodular de melanoma (HR 2,2; IC 95% HR:1,0-4,8) se mantuvieron en el modelo predictivo final. Conclusiones Nuestros resultados sugieren que unos niveles de vitamina D deficientes en el diagnóstico de melanoma no se asocian a un mayor riesgo de desarrollar un CNC. Sin embargo, en una edad > 60 y el subtipo nodular sí que aumentan el riesgo de desarrollar un CNC (AU)

Background Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). Materials and methods A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan–Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. Results Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5–7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0–4.8) were included in the final model. Conclusions Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development (AU)

Avelumab to treat Merkel cell carcinoma: real-life experience in a dedicated oncology center. / Avelumab en el tratamiento del carcinoma de células de Merkel: experiencia en vida real en un centro monográfico oncológico.

The arrival of immunotherapy has revolutioned the management of patients with metastatic Merkel cell carcinoma (MCC). We conducted an observational, retrospective study of 14 cases treated with avelumab. The response rate was 57%: complete response was reached in 29% of patients, and partial responses in 29%. The drug proved effective in 83% (5/6) of the patients with a single metastatic site. However, the disease progressed in 75% (3/4) of the patients with bone metastases. PD1-L expression, MCC polyomavirus (MCPyV) positivity, and an impaired neutrophil-to-lypmhocyte ratio (NLR) could not be associated with responses to the therapy. Avelumab is an effective and safe drug for the management of advanced MCC, and its effectiveness appears to be impacted by the number and location of metastases.

Nodular Type but Not Vitamin D Levels Increases the Risk of Second Primary Cancers in Melanoma Patients: An Observational Study of 663 Patients. / [Artículo traducido] El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes.

BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.

Nodular type but not vitamin D levels increases the risk of second primary cancers in melanoma patients: An observational study of 663 patients.

BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.

High- and intermediate-risk susceptibility variants in melanoma families from the Mediterranean area: A multicentre cohort from the MelaNostrum Consortium.

BACKGROUND: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark-skinned individuals, are underrepresented. OBJECTIVES: We report a comprehensive pooled analysis of established high- and intermediate-penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium. METHODS: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country. RESULTS: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3-19.7), >3 affected members (OR 2.6; 95% CI 1.3-5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4-9.4) in the family (AUC 0.76, 95% CI 0.71-0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0-2.0 and OR 4.3; 95% CI 1.2-14.6, respectively). CONCLUSIONS: Variants in known high-penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment.

La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en sarcoma pleomórfico dérmico / Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma

Introducción y objetivo El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados En el análisis univariado, la recidiva tumoral (p<0,001), la necrosis (p=0,020), la infiltración linfovascular (p=0,037), la infiltración perineural (p=0,041) y el número de mitosis (categorizado en categorizado en <18 y ≥18 por 10 campos de gran aumento) (p=0,093), se asociaron a una menor supervivencia libre de enfermedad. En el análisis multivariado, el número de mitosis (categorizado en <18 y ≥18) y la infiltración linfovascular (p<0,05) se asociaron a una menor supervivencia libre de enfermedad. Conclusión El SPD es un tumor agresivo, en el que la presencia de un alto recuento mitótico (≥18) y/o invasión linfovascular se asocian a un mayor riesgo de recidiva y a una peor supervivencia libre de enfermedad. La necrosis y la infiltración perineural, también son hallazgos que probablemente se asocien a una mayor agresividad tumoral (AU)

Background and objective Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. Material and methods Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. Results In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). Conclusions PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness (AU)

[Translated article] Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma / La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en el sarcoma pleomórfico dérmico

Background and objective Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. Material and methods Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. Results In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). Conclusions PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness (AU)

Introducción y objetivo El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados En el análisis univariado, la recidiva tumoral (p<0,001), la necrosis (p=0,020), la infiltración linfovascular (p=0,037), la infiltración perineural (p=0,041) y el número de mitosis (categorizado en categorizado en <18 y ≥18 por 10 campos de gran aumento) (p=0,093), se asociaron a una menor supervivencia libre de enfermedad. En el análisis multivariado, el número de mitosis (categorizado en <18 y ≥18) y la infiltración linfovascular (p<0,05) se asociaron a una menor supervivencia libre de enfermedad. Conclusión El SPD es un tumor agresivo, en el que la presencia de un alto recuento mitótico (≥18) y/o invasión linfovascular se asocian a un mayor riesgo de recidiva y a una peor supervivencia libre de enfermedad. La necrosis y la infiltración perineural, también son hallazgos que probablemente se asocien a una mayor agresividad tumoral (AU)

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)

El lentigo maligno: actualización y claves en el diagnóstico y el tratamiento / Update on Lentigo Maligna: Diagnostic Signs and Treatment

El lentigo maligno es un melanoma cutáneo in situ que asienta en zonas con daño solar acumulado. Su presentación más habitual es como una mancha irregularmente pigmentada de crecimiento lento y progresivo localizada en la cara de un paciente añoso. Aunque el porcentaje real de casos de lentigo maligno que evoluciona a formas invasoras es desconocido, se calcula que supone entre un 2 y un 5% de los casos. Tanto el diagnóstico clínico como histopatológico del lentigo maligno puede suponer un reto, especialmente en casos precoces o atípicos. Su tratamiento también puede suponer un desafío por su localización en áreas muy visibles y por su tamaño frecuentemente considerable, lo que tiene implicaciones estéticas y ocasionalmente también funcionales derivadas de la cirugía. En este trabajo revisamos las claves clínicas e histopatológicas para facilitar el diagnóstico del lentigo maligno. También revisamos las opciones de tratamiento con especial atención a la cirugía (AU)

Lentigo maligna is an in situ cutaneous melanoma that arises in sun-damaged skin. Its most common presentation is a progressive, slow-growing, irregularly pigmented spot on the face of older patients. Although the exact percentage of Lentigo maligna that progresses to invasive tumors is unknown, it is thought to lie between 2% and 5%. Both the clinical and histologic diagnosis of Lentigo maligna can be challenging, especially in patients with early-stage or atypical disease. Treatment also holds challenges, because lesions are located in highly visible areas and are often large. Surgery can thus compromise cosmetic and sometimes functional outcomes. We review clinical and histopathological findings that can facilitate the diagnosis of Lentigo maligna. We also examine treatment options, with a focus on surgery (AU)

[Translated article] Update on Lentigo Maligna: Diagnostic Signs and Treatment / El lentigo maligno: actualización y claves en el diagnóstico y el tratamiento

Lentigo maligna is an in situ cutaneous melanoma that arises in sun-damaged skin. Its most common presentation is a progressive, slow-growing, irregularly pigmented spot on the face of older patients. Although the exact percentage of Lentigo maligna that progresses to invasive tumors is unknown, it is thought to lie between 2% and 5%. Both the clinical and histologic diagnosis of Lentigo maligna can be challenging, especially in patients with early-stage or atypical disease. Treatment also holds challenges, because lesions are located in highly visible areas and are often large. Surgery can thus compromise cosmetic and sometimes functional outcomes. We review clinical and histopathological findings that can facilitate the diagnosis of Lentigo maligna. We also examine treatment options, with a focus on surgery (AU)

El lentigo maligno es un melanoma cutáneo in situ que asienta en zonas con daño solar acumulado. Su presentación más habitual es como una mancha irregularmente pigmentada de crecimiento lento y progresivo localizada en la cara de un paciente añoso. Aunque el porcentaje real de casos de lentigo maligno que evoluciona a formas invasoras es desconocido, se calcula que supone entre un 2 y un 5% de los casos. Tanto el diagnóstico clínico como histopatológico del lentigo maligno puede suponer un reto, especialmente en casos precoces o atípicos. Su tratamiento también puede suponer un desafío por su localización en áreas muy visibles y por su tamaño frecuentemente considerable, lo que tiene implicaciones estéticas y ocasionalmente también funcionales derivadas de la cirugía. En este trabajo revisamos las claves clínicas e histopatológicas para facilitar el diagnóstico del lentigo maligno. También revisamos las opciones de tratamiento con especial atención a la cirugía (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.

Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma. / La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en sarcoma pleomórfico dérmico.

BACKGROUND AND OBJECTIVE: Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. MATERIAL AND METHODS: Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. RESULTS: In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). CONCLUSIONS: PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness.

Update on Lentigo Maligna: Diagnostic Signs and Treatment. / El lentigo maligno: actualización y claves en el diagnóstico y el tratamiento.

Lentigo maligna is an in situ cutaneous melanoma that arises in sun-damaged skin. Its most common presentation is a progressive, slow-growing, irregularly pigmented spot on the face of older patients. Although the exact percentage of Lentigo maligna that progresses to invasive tumors is unknown, it is thought to lie between 2% and 5%. Both the clinical and histologic diagnosis of Lentigo maligna can be challenging, especially in patients with early-stage or atypical disease. Treatment also holds challenges, because lesions are located in highly visible areas and are often large. Surgery can thus compromise cosmetic and sometimes functional outcomes. We review clinical and histopathological findings that can facilitate the diagnosis of Lentigo maligna. We also examine treatment options, with a focus on surgery.

Análisis de las características de la docencia de pregrado de Dermatología en las universidades españolas. ¿Los contenidos teóricos se aproximan a la casuística de los médicos de Atención Primaria y dermatólogos generales? / Analysis of Undergraduate Dermatology Syllabi at Spanish Universities: Does the Weight of Theoretical Content Match the Skin Conditions Seen in Primary Care and General Dermatology Practices?

Introducción La docencia de pregrado de Dermatología varía entre las casi 50 facultades de Medicina españolas. El presente estudio pretende describir las características de las asignaturas y analizar si la carga lectiva de los temarios se ajusta a la casuística de los médicos de Atención Primaria y dermatólogos generales del sistema de salud español. Material y método Estudio de corte transversal realizado en 2021-2022. Se recabaron datos de universidades a partir de las guías docentes. Se comparó la carga docente de una universidad pública y otra privada con la carga asistencial de médicos de familia y dermatólogos a partir de estudios previos. Resultados La mayor parte de las facultades imparten Dermatología como asignatura semestral, con una mediana de 4,5 créditos, con una media de 24 temas teóricos y 9 temas en seminarios y talleres. Existe una clara divergencia entre la carga docente relativa de los temas teóricos y la carga asistencial por enfermedades cutáneas en Atención Primaria y Dermatología general. Discusión La carga lectiva infrarrepresenta en gran medida las enfermedades cutáneas más comúnmente consultadas en Atención Primaria y Dermatología general. Resulta oportuno reevaluar qué contenidos deben adquirir o recuperar una mayor representación en la carga docente de la asignatura de Dermatología. Con base en los resultados obtenidos, consideramos óptimo incrementar, idealmente mediante metodologías de apoyo a la docencia teórica, la carga docente referida a cuadros de dermatitis, dermatosis infecciosas, acné, psoriasis, urticaria y, finalmente, las neoplasias benignas y su diagnóstico diferencial con las malignas (AU)

Introduction Undergraduate dermatology courses vary in the nearly 50 Spanish medical faculties that teach the subject. This study aimed to describe the characteristics of these courses and to analyze whether the weight assigned to dermatology topics reflect the caseloads of primary care physicians and general dermatologists in the Spanish national health system. Material and method Cross-sectional study of syllabi used in Spanish medical faculties during the 2021-2022 academic year. We determined the number of teaching hours in public and private university curricula and compared the weight of dermatology topics covered to the dermatology caseloads of primary care physicians and general dermatologists as reported in published studies. Results Most medical faculties taught dermatology for one semester. The median number of credits offered was 4.5. On average, lectures covered 24 theoretical topics, and seminars and workshops covered 9 topics. We identified a clear disparity between the percentage of time devoted to dermatology topics in course lectures and the skin conditions usually managed in primary care and general dermatology practices. Discussion The skin diseases most commonly treated by primary care physicians and general dermatologists are underrepresented in the curricula of Spanish medical faculties. The topics that should be given more weight in syllabi, or recovered for inclusion in dermatology courses, should be re-examined. Our findings show that the topics that ideally should be emphasized more are types of dermatitis, infectious skin diseases, acne, psoriasis, rashes, and the differential diagnosis of benign and malignant neoplasms. There should be additional support for the theoretical teaching of these topics (AU)

[Translated article] Analysis of Undergraduate Dermatology Syllabi at Spanish Universities: Does the Weight of Theoretical Content Match the Skin Conditions Seen in Primary Care and General Dermatology Practices? / Análisis de las características de la docencia de pregrado de Dermatología en las universidades españolas. ¿Los contenidos teóricos se aproximan a la casuística de los médicos de Atención Primaria y dermatólogos generales?

Introduction Undergraduate dermatology courses vary in the nearly 50 Spanish medical faculties that teach the subject. This study aimed to describe the characteristics of these courses and to analyze whether the weight assigned to dermatology topics reflect the caseloads of primary care physicians and general dermatologists in the Spanish national health system. Material and method Cross-sectional study of syllabi used in Spanish medical faculties during the 2021-2022 academic year. We determined the number of teaching hours in public and private university curricula and compared the weight of dermatology topics covered to the dermatology caseloads of primary care physicians and general dermatologists as reported in published studies. Results Most medical faculties taught dermatology for one semester. The median number of credits offered was 4.5. On average, lectures covered 24 theoretical topics, and seminars and workshops covered 9 topics. We identified a clear disparity between the percentage of time devoted to dermatology topics in course lectures and the skin conditions usually managed in primary care and general dermatology practices. Discussion The skin diseases most commonly treated by primary care physicians and general dermatologists are underrepresented in the curricula of Spanish medical faculties. The topics that should be given more weight in syllabi, or recovered for inclusion in dermatology courses, should be re-examined. Our findings show that the topics that ideally should be emphasized more are types of dermatitis, infectious skin diseases, acne, psoriasis, rashes, and the differential diagnosis of benign and malignant neoplasms. There should be additional support for the theoretical teaching of these topics (AU)

Introducción La docencia de pregrado de Dermatología varía entre las casi 50 facultades de Medicina españolas. El presente estudio pretende describir las características de las asignaturas y analizar si la carga lectiva de los temarios se ajusta a la casuística de los médicos de Atención Primaria y dermatólogos generales del sistema de salud español. Material y método Estudio de corte transversal realizado en 2021-2022. Se recabaron datos de universidades a partir de las guías docentes. Se comparó la carga docente de una universidad pública y otra privada con la carga asistencial de médicos de familia y dermatólogos a partir de estudios previos. Resultados La mayor parte de las facultades imparten Dermatología como asignatura semestral, con una mediana de 4,5 créditos, con una media de 24 temas teóricos y 9 temas en seminarios y talleres. Existe una clara divergencia entre la carga docente relativa de los temas teóricos y la carga asistencial por enfermedades cutáneas en Atención Primaria y Dermatología general. Discusión La carga lectiva infrarrepresenta en gran medida las enfermedades cutáneas más comúnmente consultadas en Atención Primaria y Dermatología general. Resulta oportuno reevaluar qué contenidos deben adquirir o recuperar una mayor representación en la carga docente de la asignatura de Dermatología. Con base en los resultados obtenidos, consideramos óptimo incrementar, idealmente mediante metodologías de apoyo a la docencia teórica, la carga docente referida a cuadros de dermatitis, dermatosis infecciosas, acné, psoriasis, urticaria y, finalmente, las neoplasias benignas y su diagnóstico diferencial con las malignas (AU)

Relevancia clínica de los angiomas en cereza / Clinical Relevance of Cherry Angiomas

Los angiomas en cereza son los tumores vasculares cutáneos más frecuentes. Son muy prevalentes en la población general y esta prevalencia aumenta con la edad. Aunque, en sus primeras descripciones en la literatura, a finales del siglo XIX, se relacionaron con el cáncer, dicha asociación no pudo demostrarse posteriormente por lo que, durante muchas décadas, se han considerado unas lesiones asociadas al proceso del envejecimiento sin otro significado clínico particular. Sin embargo, en los últimos años, han sido objeto de un mayor interés al ser publicados algunos estudios que muestran una asociación con la exposición a diversos tóxicos y fármacos, enfermedades malignas y no malignas y la inmunosupresión que pueden ayudar a conocer mejor su etiopatogenia y su relevancia clínica (AU)

Cherry angiomas are the most common vascular tumors of the skin. They are particularly prevalent in the general population and become more common with age. Although an association with cancer was suggested at the end of the 19th century, when these tumors were first described, it could not be demonstrated. For many decades, therefore, cherry angiomas were considered to have no clinical relevance other than their association with age. A number of studies in recent years, however, have shown a link between cherry angiomas and exposure to various toxic substances and medications, benign and malignant diseases, and immunosuppression, rekindling interest in these lesions and providing clues for a better understanding of their etiology, pathophysiology, and clinical relevance (AU)