Lower limb cutaneous melanoma surgery: location matters.

The anatomical location of cutaneous melanoma is a relevant independent prognostic factor in melanoma. The aim of the study is to know the prognosis of lower limb cutaneous melanoma related to their location within the limb, regardless of the histological type, and if there are any other influencing variables. A real-world data observational study was developed. The lesions were divided depending on the location of the melanoma (thigh, leg and foot). Bivariate and multivariate analysis were performed, and melanoma-specific survival and disease-free survival rates were calculated. When these analysis were done, the results showed that, in melanomas of the lower limb, location on the foot presented a lower melanoma-specific survival rate compared to more proximal locations, and only the anatomical location presents statistical significance to discriminate cases with a higher mortality risk and a lower disease-free survival rate among distal melanomas (mainly on the foot). In conclusion, this study confirms that a more distal location of lower limb cutaneous melanoma is a relevant prognostic factor.Trial registration number NCT04625491 retrospectively registered.

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population.

BACKGROUND: Ectodermal dysplasias (ED) are a group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives. An attenuated phenotype is considered a non-syndromic trait when the patient is affected by only one impaired ectodermal structure, such as in non-syndromic tooth agenesis (NSTA) disorder. Hypohidrotic ectodermal dysplasia (HED) is the most highly represented ED. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common subtype, with an incidence of 1/50,000-100,000 males, and is associated with the EDA gene (Xq12-q13.1); the dominant and recessive subtypes involve the EDAR (2q13) and EDARADD (1q42.3) genes, respectively. The WNT10A gene (2q35) is associated more frequently with NSTA. Our goal was to determine the mutational spectrum in a cohort of 72 Spanish patients affected by one or more ectodermal derivative impairments referred to as HED (63/72) or NSTA (9 /72) to establish the prevalence of the allelic variants of the four most frequently associated genes. Sanger sequencing of the EDA, EDAR, EDARADD and WNT10A genes and multiplex ligation-dependent probe amplification (MLPA) were performed. RESULTS: A total of 61 children and 11 adults, comprising 50 males and 22 females, were included. The average ages were 5.4 and 40.2 years for children and adults, respectively. A molecular basis was identified in 51/72 patients, including 47/63 HED patients, for whom EDA was the most frequently involved gene, and 4/9 NSTA patients, most of whom had variants of WNT10A. Among all the patients, 37/51 had variants of EDA, 8/51 had variants of the WNT10A gene, 4/51 had variants of EDAR and 5/51 had variants of EDARADD. In 42/51 of cases, the variants were inherited according to an X-linked pattern (27/42), with the remaining showing an autosomal dominant (10/42) or autosomal recessive (5/42) pattern. Among the NSTA patients, 3/9 carried pathogenic variants of WNT10A and 1/9 carried EDA variants. A total of 60 variants were detected in 51 patients, 46 of which were different, and out of these 46 variants, 12 were novel. CONCLUSIONS: This is the only molecular study conducted to date in the Spanish population affected by ED. The EDA, EDAR, EDARADD and WNT10A genes constitute the molecular basis in 70.8% of patients with a 74.6% yield in HED and 44.4% in NSTA. Twelve novel variants were identified. The WNT10A gene has been confirmed as the second molecular candidate that has been identified and accounts for one-half of non-EDA patients and one-third of NSTA patients. Further studies using next generation sequencing (NGS) will help to identify other contributory genes in the remaining uncharacterized Spanish patients.

NKG2D Polymorphism in Melanoma Patients from Southeastern Spain.

BACKGROUND: Natural killer (NK) and CD8+ T cells are involved in the immune response against melanoma. C-Type lectin-like NK cell receptors are located in the Natural Killer Complex (NKC) region 12p13.2-p12.3 and play a critical role in regulating the activity of NK and CD8+ T cells. An association between polymorphisms in the NKC region, including the NKG2D gene and NKG2A promoter, and the risk of cancer has been previously described. The aim of this study was to analyze the association of polymorphisms in the NKC region with cutaneous melanoma in patients from southeastern Spain. METHODS: Seven single-nucleotide polymorphisms (SNPs) in the NKG2D gene (NKC3,4,7,9,10,11,12), and one SNP in the NKG2A promoter (NKC17) were genotyped by a TaqMan 5' Nuclease Assay in 233 melanoma patients and 200 matched healthy controls. RESULTS: A linkage disequilibrium analysis of the SNPs performed in the NKC region revealed two blocks of haplotypes (Hb-1 and Hb-2) with 14 and seven different haplotype subtypes, respectively. The third most frequent haplotype from the block Hb-2-NK3 (CAT haplotype)-was significantly more frequent on melanoma patients than on healthy controls (p = 0.00009, Pc = 0.0006). No further associations were found when NKC SNPs were considered independently. CONCLUSIONS: Our results suggest an association between NKG2D polymorphisms and the risk of cutaneous malignant melanoma.

MHC class I chain-related gene a diversity in patients with cutaneous malignant melanoma from southeastern Spain.

A limited number of studies have been performed so far on the polymorphism in the transmembrane region (exon 5) of the major histocompatibility complex class I chain-related gene A (MICA) in patients with melanoma. However, the influence of MICA polymorphism in extracellular domains (exons 2, 3, and 4) has not been investigated on melanoma disease. This study aims to characterize the influence of extracellular MICA polymorphism, and its previously described linkage disequilibrium with HLA-B locus, on patients with cutaneous melanoma from southeastern Spain. For this purpose, MICA and HLA-B genotyping was performed in 233 patients and 200 ethnically matched controls by luminex technology. Patients were classified according to the presence of methionine or valine at codon 129 of MICA gene. We found a high frequency of MICA(*)009 in melanoma patients compared with controls (P = 0.002, Pc = 0.03). Our results also showed an association between MICA(*)009 and HLA-B(*)51 alleles in both patients and controls. This association was stronger in patients than controls (P = 0.015). However, a multivariate logistic regression model showed that neither MICA(*)009 nor the combination MICA(*)009/HLA-B(*)51 was associated with melanoma susceptibility. No relationship was observed between MICA-129 dimorphism and melanoma nor when MICA polymorphism was evaluated according to clinical findings at diagnosis.

Cutaneous leishmaniasis in a patient receiving infliximab.

Leishmaniasis is endemic in the Mediterranean region, and the prevalence of latent infection in this area is high. Treatment with tumour necrosis factor (TNF) antagonists represents a major breakthrough in the treatment of several inflammatory diseases, including psoriasis. Reports describing opportunistic leishmaniasis in European patients treated with TNF-α antagonist drugs are rapidly accumulating. We describe a case of cutaneous leishmaniasis in a patient treated with infliximab and corticosteroids.

Localización anatómica del tumor primario como variable a considerar en la biopsia selectiva del ganglio centinela del melanoma cutáneo / Anatomical location of the primary tumor as a variable to be considered in sentinel node biopsy of cutaneous melanoma

Introducción. La localización anatómica del melanoma cutáneo se ha considerado como un factor pronóstico independiente. En este trabajo se trata de comprobar si la localización del tumor primario influye en la detección del ganglio centinela en el melanoma cutáneo. Pacientes y método. Se ha estudiado a 212 pacientes con melanoma cutáneo primario (96 en los miembros, 89 en el tronco y 27 en la cabeza o el cuello) en los que se realizó la biopsia del ganglio centinela. Se estudió la adecuada localización gammagráfica y quirúrgica y se compararon las variables epidemiológicas e histopatológicas, el número de drenajes por lesión y de ganglios centinela por drenaje y la positividad del estudio de los ganglios. Para los drenajes procedentes de los tumores de la cabeza y el cuello se estudió el drenaje hacia territorio de la glándula salival como variable relacionada con la localización del ganglio centinela. Resultados. La localización fue peor para los tumores de cabeza y cuello (88,8%), tanto gammagráfica (p <0,001) como quirúrgica (p <0,0005), especialmente para los ganglios adyacentes a las glándulas salivales (p <0,0005). Los melanomas del tronco presentan un mayor número y variabilidad en sus drenajes (p <0,0005), aunque sin diferencias en el número de ganglios centinela por drenaje linfático (p = 0,455). Conclusiones. Los melanomas cutáneos localizados en la cabeza y el cuello presentaron más fallos en la identificación del ganglio centinela. La localización del ganglio centinela adyacente a una glándula salival es un factor que influye en su adecuada detección. Los melanomas cutáneos del tronco presentan un mayor número de drenajes por lesión que los localizados en las extremidades o en la cabeza y el cuello (AU)

Introduction. The anatomical location of cutaneous melanoma has been suggested to be an independent prognostic factor. The aim of the present study was to determine whether the location of the primary tumor influences sentinel node detection in cutaneous melanoma. Patients and method. Two hundred twelve patients with primary cutaneous melanoma (96 of the limbs, 89 of the trunk and 27 of the head or neck) who underwent sentinel lymph node biopsy were studied. Adequate lymphoscintigraphic and surgical localization was evaluated and epidemiological and histopathological variables, the number of lymph nodes draining the site of the primary lesion, sentinel nodes per drainage basin, and tumor-positive nodes were compared. Results. Localization was less successful for tumors of the head and neck (88.8%), both with lymphoscintigraphy (P<.001) and surgery (P<.0005), especially for lymph nodes adjacent to salivary glands (P<.0005). Melanomas of the trunk showed a greater number of nodes per lesion and wider variability in drainage pathways (P<.0005), although there were no differences in the number of sentinel nodes per drainage basin (P=0455). Conclusions. Sentinel node detection with less successful in cutaneous melanomas located in the head and neck. Location of the sentinel node adjacent to a salivary gland is a factor that influences its detection. Cutaneous melanomas of the trunk showed a higher number of draining nodes per lesion than those located in the limbs or head and neck (AU)

[Anatomical location of the primary tumor as a variable to be considered in sentinel node biopsy of cutaneous melanoma]. / Localización anatómica del tumor primario como variable a considerar en la biopsia selectiva del ganglio centinela del melanoma cutáneo.

INTRODUCTION: The anatomical location of cutaneous melanoma has been suggested to be an independent prognostic factor. The aim of the present study was to determine whether the location of the primary tumor influences sentinel node detection in cutaneous melanoma. PATIENTS AND METHOD: Two hundred twelve patients with primary cutaneous melanoma (96 of the limbs, 89 of the trunk and 27 of the head or neck) who underwent sentinel lymph node biopsy were studied. Adequate lymphoscintigraphic and surgical localization was evaluated and epidemiological and histopathological variables, the number of lymph nodes draining the site of the primary lesion, sentinel nodes per drainage basin, and tumor-positive nodes were compared. RESULTS: Localization was less successful for tumors of the head and neck (88.8%), both with lymphoscintigraphy (P<.001) and surgery (P<.0005), especially for lymph nodes adjacent to salivary glands (P<.0005). Melanomas of the trunk showed a greater number of nodes per lesion and wider variability in drainage pathways (P<.0005), although there were no differences in the number of sentinel nodes per drainage basin (P=.455). CONCLUSIONS: Sentinel node detection with less successful in cutaneous melanomas located in the head and neck. Location of the sentinel node adjacent to a salivary gland is a factor that influences its detection. Cutaneous melanomas of the trunk showed a higher number of draining nodes per lesion than those located in the limbs or head and neck.

Carcinoma de mama en varón / Male breast cancer

Se presentan 2 pacientes en los que, tras la biopsia de sus lesiones cutáneas mamarias, se diagnosticaron sendos carcinomas, en uno trabecular y en el otro ductal infiltrante. En ambos casos el motivo de consulta original fue totalmente distinto, y las lesiones mamarias fueron hallazgos casuales tras la adecuada exploración física. Los factores de riesgo relacionados eran un traumatismo mamario en el primero y la existencia de enfermedad prostática previa, obesidad y edad avanzada en el segundo. El cáncer de mama en el varón es poco frecuente. Aunque en el 25% de los casos la primera manifestación suele ser cutánea, ésta no suele ser el motivo de consulta. El diagnóstico precoz mejora el pronóstico, al igual que en la mujer, por lo que es necesario conocer las manifestaciones cutáneas, pues éstas pueden constituir el signo fundamental para establecer un rápido diagnóstico e instaurar un tratamiento adecuado (AU)

Biopsia selectiva del ganglio centinela en el melanoma mediante localización con linfogammagrafía preoperatoria y sonda de detección gamma intraoperatoria / Sentinel node biopsy in melanoma using preoperative lymphoscintigraphy and intraoperative handheld gamma probe

FUNDAMENTOS: Se refiere la experiencia para la detección del ganglio centinela en el melanoma utilizando únicamente la linfogammagrafía preoperatoria y trazador radiactivo con sonda de detección de radiación gamma intraoperatoria. PACIENTES Y MÉTODO: Se estudió a 60 pacientes con melanoma en estadios I-II, a quienes se realizó biopsia selectiva del ganglio centinela mediante su localización con sulfuro coloidal marcado con Tc-99m. A todos se les efectuó una gammagrafía preoperatoria y se trató de localizar el ganglio centinela con una sonda de detección de radiación gamma. Se han estudiado los resultados de la gammagrafía preoperatoria, la eficacia técnica en la localización intraoperatoria, así como los resultados anatomopatológicos y del seguimiento de los pacientes. RESULTADOS: La tasa de detección preoperatoria fue del 98,3 por ciento, con una media de 1,17 drenajes por lesión, siendo múltiples especialmente en los melanomas de tronco. La localización intraoperatoria (eficacia técnica) fue del 98,48 por ciento, con dificultades para su localización en la región parotídea. En el estudio histopatológico fueron fundamentales las técnicas de inmunohistoquímica con HMB45, resultando positivos un 10 por ciento, por lo que se evitó la linfadenectomía en el 90 por ciento de los casos. No se observaron recidivas y las metástasis se dieron en casos inabordables. La morbilidad de la técnica fue significativamente menor que la de la linfadenectomía. CONCLUSIONES: La linfogammagrafía preoperatoria y el uso de sonda de detección de radiación gamma, como técnica de localización del ganglio centinela en el melanoma, tienen una elevada eficacia técnica, permiten detectar drenajes múltiples y posibilitan un abordaje muy selectivo y con disección mínima (AU)