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.

Carcinoma basocelular histológicamente agresivo con especial atención a la infiltración galeal del cuero cabelludo / Histologically Agressive Basal Cell Carcinoma With Particular Emphasis On Galeal Infiltration Of The Scalp

En el manejo del carcinoma basocelular (CBC) es fundamental conocer los factores de riesgo que predicen un comportamiento más agresivo. Estos factores de riesgo se dividen esencialmente en factores clínicos y en factores histopatológicos. En este trabajo revisamos e ilustramos los hallazgos histopatológicos predictivos de agresividad en el CBC. Dichos factores histopatológicos predictivos de agresividad incluyen las variedades histológicas clásicas de CBC «agresivas»: la morfeiforme, la infiltrativa, la micronodular, la metatípica, la basoescamosa y el CBC con diferenciación sarcomatoide. Pero, aparte de las variedades referidas, existen también 2hallazgos histopatológicos asociados a CBC agresivos, uno bien conocido y reflejado en la literatura, que es la infiltración perineural de filetes nerviosos de más de 0,1mm de diámetro o subdérmicos, y el otro es la extensión subgaleal. La infiltración galeal no está bien reconocida como tal en literatura, pero es un factor predictivo de agresividad importante en el CBC y queremos llamar la atención sobre él (AU)

Familiarity with predictors of more aggressive behavior is crucial to the management of basal cell carcinoma (BCC). Risk factors for aggressive BCC are essentially divided into clinical and histopathologic factors. In this review we examine histopathologic features predictive of aggressiveness in BCC. The morpheaform, infiltrative, micronodular, metatypical, and basosquamous subtypes and BCC with sarcomatoid differentiation are classically considered predictive of aggressive behavior. However, 2 other features associated with aggressive BCC are perineural invasion (invasion of nerves below the dermis or nerves larger than 0.1mm in caliber) and subgaleal extension. While the former is well known and widely described in the literature, the latter is not generally recognized as a risk factor, even though it is predictive of highly aggressive behavior. In this review, we draw attention to its importance (AU)

[Translated article] Histologically agressive basal cell carcinoma with particular emphasis on galeal infiltration of the scalp / Carcinoma basocelular histológicamente agresivo con especial atención a la infiltración galeal del cuero cabelludo

Familiarity with predictors of more aggressive behavior is crucial to the management of basal cell carcinoma (BCC). Risk factors for aggressive BCC are essentially divided into clinical and histopathologic factors. In this review we examine histopathologic features predictive of aggressiveness in BCC. The morpheaform, infiltrative, micronodular, metatypical, and basosquamous subtypes and BCC with sarcomatoid differentiation are classically considered predictive of aggressive behavior. However, 2 other features associated with aggressive BCC are perineural invasion (invasion of nerves below the dermis or nerves larger than 0.1mm in caliber) and subgaleal extension. While the former is well known and widely described in the literature, the latter is not generally recognized as a risk factor, even though it is predictive of highly aggressive behavior. In this review, we draw attention to its importance (AU)

En el manejo del carcinoma basocelular (CBC) es fundamental conocer los factores de riesgo que predicen un comportamiento más agresivo. Estos factores de riesgo se dividen esencialmente en factores clínicos y en factores histopatológicos. En este trabajo revisamos e ilustramos los hallazgos histopatológicos predictivos de agresividad en el CBC. Dichos factores histopatológicos predictivos de agresividad incluyen las variedades histológicas clásicas de CBC «agresivas»: la morfeiforme, la infiltrativa, la micronodular, la metatípica, la basoescamosa y el CBC con diferenciación sarcomatoide. Pero, aparte de las variedades referidas, existen también 2hallazgos histopatológicos asociados a CBC agresivos, uno bien conocido y reflejado en la literatura, que es la infiltración perineural de filetes nerviosos de más de 0,1mm de diámetro o subdérmicos, y el otro es la extensión subgaleal. La infiltración galeal no está bien reconocida como tal en literatura, pero es un factor predictivo de agresividad importante en el CBC y queremos llamar la atención sobre él (AU)

Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Real-World Experience in a Monographic Oncology Center / Cemiplimab en el carcinoma de células escamosas cutáneo avanzado: experiencia del mundo real en un centro oncológico monográfico

Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile (AU)

El manejo del carcinoma de células escamosas cutáneo (cSCC) avanzado es complicado, siendo modesta la eficacia de muchos de los fármacos sistémicos disponibles. Cemiplimab ha demostrado su eficacia en el tratamiento del cSCC avanzado en ensayos clínicos, pero los datos del mundo real siguen siendo limitados. Con el objetivo de evaluar la eficacia de cemiplimab en un entorno clínico del mundo real, realizamos un estudio observacional prospectivo de 13 pacientes con cSCC avanzado. Seis pacientes (46%) tenían enfermedad localmente avanzada, mientras que 7 (54%) tenían enfermedad metastásica. Un total de 8 pacientes (62%) respondieron a cemiplimab, 5 (38%) mostraron una respuesta parcial y 3 (23%) mostraron una respuesta completa. Cuatro pacientes con respuesta parcial inicial presentaron una progresión de la enfermedad subsiguiente durante el seguimiento. Seis pacientes (46%) desarrollaron efectos secundarios, siendo leve la mayoría de los mismos (G1). La supervivencia libre de progresión fue de 5,9 meses, con un seguimiento medio de 9 meses. En conclusión, cemiplimab demostró su utilidad en el tratamiento del cSCC avanzado, con unas tasas de respuesta aceptables, un número destacable de respuestas completas y un perfil de seguridad muy bueno (AU)

[Artículo traducido] Cemiplimab en el carcinoma de células escamosas cutáneo avanzado: experiencia del mundo real en un centro oncológico monográfico / Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Real-World Experience in a Monographic Oncology Center

El manejo del carcinoma de células escamosas cutáneo (cSCC) avanzado es complicado, siendo modesta la eficacia de muchos de los fármacos sistémicos disponibles. Cemiplimab ha demostrado su eficacia en el tratamiento del cSCC avanzado en ensayos clínicos, pero los datos del mundo real siguen siendo limitados. Con el objetivo de evaluar la eficacia de cemiplimab en un entorno clínico del mundo real, realizamos un estudio observacional prospectivo de 13 pacientes con cSCC avanzado. Seis pacientes (46%) tenían enfermedad localmente avanzada, mientras que 7 (54%) tenían enfermedad metastásica. Un total de 8 pacientes (62%) respondieron a cemiplimab, 5 (38%) mostraron una respuesta parcial y 3 (23%) mostraron una respuesta completa. Cuatro pacientes con respuesta parcial inicial presentaron una progresión de la enfermedad subsiguiente durante el seguimiento. Seis pacientes (46%) desarrollaron efectos secundarios, siendo leve la mayoría de los mismos (G1). La supervivencia libre de progresión fue de 5,9 meses, con un seguimiento medio de 9 meses. En conclusión, cemiplimab demostró su utilidad en el tratamiento del cSCC avanzado, con unas tasas de respuesta aceptables, un número destacable de respuestas completas y un perfil de seguridad muy bueno (AU)

Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile (AU)