Recurrence factors in patients with cutaneous melanoma and positive sentinel lymph node treated in a single reference unit in Buenos Aires / Factores de recurrencia en pacientes con melanoma cu táneo y ganglio centinela positivo

Abstract Introduction : Although therapeutic advances have improved results of cutaneous melanoma (CM), senti nel node-positive patients still have substantial risk to develop recurrent disease. We aim to investigate prog nostic indicators associated with disease recurrence in positive-sentinel lymph node biopsy (SLNB) patients in a Latin-American population. Methods : Retrospective analysis of CM patients and positive-SLNB (2010-2020). Patients were divided into two groups: Group A (completion lymph node dissection, CLND), Group B (active surveillance, AS). Association of demographics, tumor data and SLN features with recurrence-free (RFS), distant metastases-free (DMFS) and melanoma specific (MSS) survival was analyzed. Results : Of 205 patients, 45 had a positive SLNB; 27(60%) belonged to Group A and 18(40%) to Group B. With a median follow-up of 36 months, 16 patients (12 in Group A and 4 in Group B) developed recurrent dis ease and estimated 5-yr RFS at any site was 60% (CI95%, 0.39 - 0.77) (44.5% in CLND group vs. 22% in AS group; P = 0.20). Estimated 5-yr DMFS and MSS: 65% (CI 95%, 0.44 - 0.81) and 73% (CI 95%, 0.59 - 0.89) with no differ ences between groups (p = 0.41 and 0.37, respectively). Independent predictors of poorer MSS were extranodal extension (ENE) and MaxSize > 2 mm of melanoma deposit in SLN. Factors independently associated with DMFS: Breslow depth > 2 mm, ENE, number (≥ 2) of posi tive SN and CLND status. Conclusion : Primary tumor and SN features in mela noma provide important prognostic information that help optimize prognosis and clinical management. AS is now the preferred approach for most positive-SLNB CM patients.

Resumen Introducción : Si bien los avances terapéuticos han permitido mejorar los resultados del melanoma cutáneo (MC), los pacientes con ganglio centinela positivo (BGCP) aún tienen riesgo elevado de desarrollar recurrencia de la enfermedad. Nuestro objetivo fue investigar in dicadores pronósticos asociados a dicho evento en una población latinoamericana. Métodos : Análisis retrospectivo de pacientes con MC y BGCP entre 2010-2020. Los pacientes se dividieron en 2 grupos: Grupo A (linfadenectomía terapéutica) y Grupo B (Vigilancia activa, VA). Se analizaron datos demográficos, tumorales y características del GC junto con sobrevida-libre de recurrencia (SLR), libre de metástasis a distancia (SLMD) y específica de melanoma (SEM). Resultados : De 205 pacientes, 45 presentaron BGCP; 27 (60%) perteneció al Grupo A y 18 (40%) al Grupo B. Con una mediana de seguimiento de 36 meses, 16 pa cientes (12 en Grupo A y 4 en Grupo B) desarrollaron enfermedad recurrente con una SLR a 5 años de 60% (IC95%: 0.39-0.77) (44.5% en Grupo B vs. 22% en Grupo A; P = 0.20). Las SLMD y SEM estimadas a 5 años fueron de 65% (CI 95%, 0.44 - 0.81) y 73% (CI 95%, 0.59 - 0.89) sin diferencias entre ambos grupos (p = 0.41 y 0.37, respec tivamente). Los predictores independientes de peor SEM fueron: extensión extranodal (ENE) y MaxSize > 2mm de depósito tumoral en GC. Los factores asociados de forma independiente con SLMD fueron Breslow >2mm, ENE, número (≥ 2) de GC positivos y el status (positividad) de la linfadenectomía. Conclusión : Características del tumor primario y del GC brindan información importante que ayuda a optimi zar el pronóstico y manejo clínico de los pacientes con MC. La VA es actualmente el abordaje de elección para la mayoría de los pacientes con BGCP.

Melanoma mucoso de la cavidad oral: Reporte de caso

El melanoma mucoso (MM) es un subtipo raro de malignidad que surge de la transformación maligna de los melanocitos. EL MM representa el 1% de todos los casos de melanoma, siendo un subtipo agresivo y con mal pronóstico, con supervivencia global a 5 años de 10-20%. El Melanoma mucoso de la cavidad oral corresponde al 0.5% de todos los tumores malignos en la cavidad oral y al 25% de los melanomas mucosos ubicados en cabeza y cuello. Tiene una distribución anatómica de predominio en el tracto sinunasal 70%, cavidad oral 20% y otras ubicaciones como larige y faringe. Algunos probables factores de riesgo descritos son: trauma mecánico crónico, etilismo, tabaquismo, formaldehído, Sin embargo su etiología permanece incierta. Presentamos el caso de una paciente Femenina de 77 años tratada exitosamente mediante maxilectomía inferior y disección selectiva cervical izquierda. (provisto por Infomedic International)

Mucosal melanoma (MM) is a rare subtype of malignancy arising from malignant transformation of melanocytes. MM accounts for 1% of all cases of melanoma, being an aggressive subtype with poor prognosis, with 5-year overall survival of 10-20%. Mucosal melanoma of the oral cavity corresponds to 0.5% of all malignant tumors in the oral cavity and 25% of mucosal melanomas located in the head and neck. It has an anatomical distribution of predominance in the sinonasal tract 70%, oral cavity 20% and other locations such as larynx and pharynx. Some probable risk factors described are chronic mechanical trauma, ethylism, smoking, formaldehyde, however its etiology remains uncertain. We present the case of a 77-year-old female patient successfully treated by inferior maxillectomy and selective left cervical dissection. (provided by Infomedic International)

Reflectance confocal microscopy - Consensus terminology glossary in Brazilian Portuguese for normal skin, melanocytic and non-melanocytic lesions

Abstract Background: Currently, there is no uniform and official terminology in Portuguese for reflectance confocal microscopy analysis, despite the increasing number of Brazilian dermatologists using this new tool. Objective: To present the terminology in Brazilian Portuguese for the description of reflectance confocal microscopy and establish the first Brazilian consensus on terms related to normal skin and cutaneous tumors. Methods: 10 Brazilian specialists from different institutions and states of Brazil were selected to evaluate the best corresponding terms in Portuguese for normal skin, melanocytic and non-melanocytic tumors. The terms used were translated from international consensuses in the English language. The modified Delphi method was used to create the consensus in 3 steps. Results: The terms considered the most appropriate in the Portuguese language to describe the findings of normal skin, melanocytic and non-melanocytic lesions in the reflectance confocal microscopy analysis were presented. Study limitations: The limitations of the present study include the number of participants and limited regional representation (only two of the five Brazilian regions were represented). Conclusion: This Brazilian consensus represents an opportunity for dermatologists and physicians specializing in cutaneous oncology to become familiar with reflectance confocal microscopy, propagating the technique in clinical and research environments to stimulate national and international publications on this subject.

Caracterización histológica del melanoma cutáneo en reportes de patología en la ciudad de Cali, 2016-2021 / Histological characterization of cutaneous melanoma in pathology reports in the city of Cali, 2016-2021

Introducción. El melanoma es la proliferación maligna de melanocitos asociado a un comportamiento agresivo. El objetivo de este estudio fue determinar las variables histológicas del melanoma cutáneo. Métodos. Estudio observacional retrospectivo, transversal descriptivo, realizado con reportes de patologías de pacientes con diagnóstico de melanoma cutáneo en un laboratorio de patología en Cali, Colombia, entre 2016-2021. Se incluyeron las variables edad, sexo, localización, subtipo, espesor de Breslow, ulceración, márgenes, mitosis, invasión linfovascular, neurotrofismo, regresión tumoral, nivel de Clark e infiltración tumoral por linfocitos. Resultados. Se obtuvieron 106 reportes y fueron excluidos 54 por duplicación. Se incluyeron 52 registros, la media de edad fue de 61 años, con una mayor frecuencia de mujeres (55,8 %). De los 33 casos donde se especificó el subtipo histológico, el más frecuente fue el de extensión superficial (66,6 %), seguido del acral lentiginoso (18,1 %) y nodular con (15,2 %). La localización más frecuente fue en extremidades (61,5 %). El espesor de Breslow más común fue IV (34,6 %) y el nivel de Clark más frecuente fue IV (34,6 %). La ulceración estuvo en el 40,4 %. El subtipo nodular fue el de presentación más agresiva, donde el 100 % presentaron espesor de Breslow IV. Conclusiones. El subtipo de melanoma más común en nuestra población fue el de extensión superficial; el segundo en frecuencia fue el subtipo acral lentiginoso, que se localizó siempre en extremidades. Más del 50 % de los melanomas tenían espesor de Breslow mayor o igual a III, lo que impacta en el pronóstico.

Background. Melanoma is the malignant proliferation of melanocytes associated with aggressive behavior. The objective of this study was to determine the histological variables of cutaneous melanoma. Methods. Observational, cross-sectional, descriptive, retrospective study carried out with reports of pathologies with a diagnosis of cutaneous melanoma in a pathology laboratory in Cali between 2016-2021. The variables were age, sex, location, subtype, Breslow thickness, ulceration, margins, mitosis, lymphovascular invasion, neurotropism, tumoral regression, Clark level and tumor infiltration by lymphocytes. Results. One hundred and six reports were obtained and 54 were excluded due to duplication. A descriptive analysis was made on the 52 records that were included, the mean age was 61 years, with a higher frequency in women with 55.8%. Of the 33 cases where the histological subtype was specified, the most frequent was superficial extension with 66.6%, followed by acral lentiginous with 18.1% and nodular with 15.2%. The most frequent location was in the extremities (61.5%); the most common Breslow was IV (34.6%), and the most frequent Clark was IV (34.6%). Ulceration was in 40.4%. The nodular subtype was the most aggressive presentation where 100% presented Breslow IV. Conclusions. The most common subtype of melanoma was that of superficial extension. In our population, the second most frequent was the acral lentiginous subtype, which was always located on the extremities. More than 50% of the melanomas had Breslow greater than or equal to III, which affects the prognosis.

Tumor maligno de la vaina nerviosa periférica: reporte de un caso / Malignant peripheral nerve sheath tumor, a case report

Resumen El tumor maligno de la vaina nerviosa periférica (TMVNP) es un sarcoma de alto grado de malignidad. Es poco frecuente, agresivo y generalmente se localiza en tronco y miembros inferiores. Se presenta mayormente en pacientes con neurofibormatosis tipo 1, aunque no siempre se encuentra esta asociación. Este tumorcomparte características histológicas e inmunohistoquímicas con el melanoma, lo que puede dificultar el diagnóstico. Presentamos el caso de un paciente con TMVNP, en el cual los hallazgos histológicos iniciales condujeron a un diagnósticoerróneode melanoma.

Abstract Malignant peripheral nerve sheath tumor (MPNST) is a high-grade sarcoma. It is rare, aggressive and generally located on the trunk and lower limbs. It occurs in a high percentage of patients with neurofibormatosis type 1, although this association is not always found. This tumor shares histological and immunohistochemical characteristics with melanoma, which can make diagnosis difficult. We present the case of a patient with MPNST, in whom the initial histological findings led to an erroneous diagnosis of melanoma.

Crotoxin induces cytotoxic effects in human malignant melanoma cells in both native and detoxified forms

Introduction: Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential. While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. Crotoxin (CTX), the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial. Methods and Results: This study investigates the antitumoral potential of CTX in its native and in a detoxified form, in melanoma cells. Firstly, we demonstrated that detoxified CTX presented reduced phospholipase activity. Both forms proved to be more cytotoxic to SK-MEL-28 and MeWo melanoma cells than non-tumoral cells. In SK-MEL-28 cells, where cytotoxic effects were more pronounced, native and detoxified CTX induced increased necrosis and apoptosis rates. We also confirmed the apoptosis death demonstrated by the activation of caspase-3 and 7, and the formation of apoptotic bodies. Furthermore, both CTX caused cell cycle arrest at the G2/M phase, interfering with melanoma cell proliferation. Cell migration and invasion were also suppressed by both CTX. These results confirm the antitumoral potential of CTX. Discussion: The maintenance of the antiproliferative effects in the detoxified version, with reduced enzymatic activity often liked to harm effects, supports further studies to identify active parts of the molecule responsible for the interesting effects without causing substantial toxic events, contributing to the future use of CTX-derived drugs with safety and efficacy.

Crotoxin induces cytotoxic effects in human malignant melanoma cells in both native and detoxified forms

Introduction: Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential. While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. Crotoxin (CTX), the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial. Methods and Results: This study investigates the antitumoral potential of CTX in its native and in a detoxified form, in melanoma cells. Firstly, we demonstrated that detoxified CTX presented reduced phospholipase activity. Both forms proved to be more cytotoxic to SK-MEL-28 and MeWo melanoma cells than non tumoral cells. In SK-MEL-28 cells, where cytotoxic effects were more pronounced, native and detoxified CTX induced increased necrosis and apoptosis rates. We also confirmed the apoptosis death demonstrated by the activation of caspase-3 and 7, and the formation of apoptotic bodies. Furthermore, both CTX caused cell cycle arrest at the G2/M phase, interfering with melanoma cell proliferation. Cell migration and invasion were also suppressed by both CTX. These results confirm the antitumoral potential of CTX. Discussion: The maintenance of the antiproliferative effects in the detoxified version, with reduced enzymatic activity often liked to harm effects, supports further studies to identify active parts of the molecule responsible for the interesting effects without causing substantial toxic events, contributing to the future use of CTX-derived drugs with safety and efficacy.

Unveiling novel targets in melanoma under melanogenesis stimulation and photodynamic therapy by redox proteomics

Melanogenesis- stimulated B16-F10 cells enter in a quiescent state, present inhib-ited mitochondrial respiration and increased reactive oxygen species levels. Thesealterations suggest that these cells may be under redox signaling, allowing tumorsurvival. The aim of this study was to evaluate redox-modified proteins in B16-F10 cells after melanogenesis stimulation and rose bengal-photodynamic therapy(RB-PDT). A redox proteomics label-free approach based on the biotin switchassay technique with biotin-HPDP and N-ethylmaleimide was used to assess thethiol-oxidized protein profile. Aconitase was oxidized at Cys-448 and Cys-451,citrate synthase was oxidized at Cys-202 and aspartate aminotransferase (Got2)was oxidized at Cys-272 and Cys-274, exclusively after melanogenesis stimula-tion. After RB- PDT, only guanine nucleotide-binding protein subunit beta- 2- like1 (Gnb2l1) was oxidized (Cys-168). In contrast, melanogenesis stimulation fol-lowed by RB- PDT led to the oxidation of different cysteines in Gnb2l1 (Cys-153and Cys- 249). Besides that, glyceraldehyde-3-phosphate dehydrogenase (Gapdh)presented oxidation at Cys-245, peptidyl-prolyl cis-trans isomerase A (Ppia) wasoxidized at Cys-161 and 5,6-dihydroxyindole-2-carboxylic acid oxidase (Tyrp1)was oxidized at Cys-65, Cys-30, and Cys-336 after melanogenesis stimulation fol-lowed by RB-PDT. The redox alterations observed in murine melanoma cells andidentification of possible target proteins are of great importance to further under-stand tumor resistance mechanisms.

Effectiveness and tolerance of electrochemotherapy as palliative therapy for patients with head and neck cancer and malignant melanoma and its relation to early skin reaction

Abstract Objectives To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). Methods prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n = 13), papillary thyroid carcinoma (n = 4), adenoid cystic carcinoma of parotid gland (n = 1) or malignant melanoma (n = 37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. Results Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p = 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p = 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p = 0.86). Conclusions Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. Level of evidence III.

Frequency of skin diseases in renal transplant recipients and patients with chronic kidney disease in a tertiary center: a cross-sectional study

ABSTRACT BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants' medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0-56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0-71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Proposal for the applicability of modified Breslow (measured from the basal membrane) as a predictor of survival and sentinel lymph node outcome in patients with cutaneous melanoma

Abstract Background Cutaneous melanoma is a neoplasm with a high mortality rate and risk of metastases to distant organs. The Breslow micrometric measurement is considered the most important factor for evaluating prognosis and management, measured from the granular layer to the deepest portion of the neoplasm. Despite its widespread use, the Breslow thickness measurement has some inaccuracies, such as not considering variations in the thickness of the epidermis in different body locations or when there is ulceration. Objective To evaluate the applicability of a modified Breslow measurement, measured from the basal membrane instead of from the granular layer, in an attempt to predict sentinel lymph node examination outcome and survival of patients with melanoma. Methods A retrospective and cross-sectional analysis was carried out based on the evaluation of slides stained with hematoxylin & eosin from 275 cases of melanoma that underwent sentinel lymph node biopsy from 2008 to 2021 at a reference center in Brazil. Results Analysis of the Cox model to evaluate the impact of the Breslow measurement and the modified Breslow measurement on survival showed that both methods are statistically significant. Logistic regression revealed a significant association between both measurements and the presence of metastasis in sentinel lymph nodes. Conclusion Measuring melanoma depth from the basal membrane (modified Breslow measurement) is capable of predicting survival time and sentinel lymph node outcome, as well as the conventional Breslow measurement.

Avaliação morfológica dos glóbulos periféricos nos nevos melanocíticos e no melanoma através da dermatoscopia / Melanoma and melanocytic nevi with peripheral globules: Clinical and dermoscopic features

Introdução: A morfologia e biologia do nevo melanocítico (NM) com glóbulos periféricos (GP) é descrita como parte do processo natural de evolução do nevo melanocítico sendo caracterizada como fase de crescimento. Por outro lado, os melanomas cutâneos (MC) com glóbulos periféricos ainda permanecem indefinidos. Objetivos: avaliar e descrever as características dos melanomas com glóbulos periféricos à dermatoscopia e, com isso, criar um algoritmo de conduta para facilitar o manejo das lesões melanocíticas em crescimento. Como objetivo secundário, foi realizado análise prospectiva de lesões melanocíticas com glóbulos periféricos à dermatoscopia através da utilização do algoritmo proposto previamente buscando comprovar sua aplicabilidade clínica. Materiais e métodos: Fase 1, estudo retrospectivo, foram avaliadas lesões melanocíticas com GP de 2006 a 2020. As imagens dermatoscópicas destas lesões foram avaliadas por dermatoscopista experiente, através da análise estatística foi possível desenvolver um algoritmo de conduta. Fase 2, na amostra inicial foram incluídas lesões melanocíticas com GP entre 2020 e 2023. Com esta nova amostra, foi realizada a validação do algoritmo de conduta através da aplicação estatística de um modelo preditivo. Em um segundo momento, 04 observadores avaliaram as imagens dermatoscópicas através do algoritmo proposto sendo possível estimar seu desempenho. Resultados: Fase 1, das 401 lesões, 179 foram excisadas sendo 41 melanomas. Os melanomas foram mais comuns quando localizados nos membros inferiores (p<0,1) e se apresentavam com padrão dermatoscópico desorganizado. Enquanto os nevos melanocíticos foram mais comuns no tronco e com padrão organizado. Além disso, a presença de uma das seguintes estruturas: pontos e glóbulos atípicos, estruturas vasculares atípicas ou área de borrão apresentaram associação com melanoma. Fase 2, as 55 lesões coletadas foram excisadas e adicionadas ao banco de dados final (n= 456), a partir dos valores preditos deste banco de dados, foi possível estabelecer uma curva ROC cuja área sob a curva foi de 0,834 e acurácia de 71,21%. A análise dermatoscópica de quatro observadores demonstrou área sob a curva ROC de 0,627 a 0,765. Conclusão: Lesões melanocíticas com glóbulos periféricos apresentam maior risco para melanoma quando em indivíduos acima de 30 anos de idade, se localizadas nos membros inferior e com a presença de uma ou mais das seguintes estruturas: pontos e glóbulos atípicos e/ou estruturas vasculares atípicas e/ou área de borrão. Estas características encontradas foram validadas por modelo preditivo demonstrando um bom desempenho através da análise da curva ROC e índice de acurácia dentro do esperado

Introduction: The morphology and biology of melanocytic nevus (MN) with peripheral globules (PG) is described as part of the natural process of evolution of melanocytic nevus and is characterized as a growth phase. On the other hand, cutaneous melanomas (CM) with peripheral globules remain unclear. Objectives: To evaluate and describe in detail the characteristics of melanocytic lesions with peripheral globules at dermoscopy, therefore, create an algorithm of management of growing melanocytic lesions. As a secondary objective, a prospective analysis of melanocytic lesions with peripheral globules was carried out using the previously proposed algorithm, seeking to prove its clinical applicability. Materials and methods: Phase 1, retrospective study, melanocytic lesions with PG were evaluated from 2006 to 2020. The dermoscopic images of these lesions were evaluated by an experienced dermatoscopist, through statistical analysis it was possible to develop a management algorithm. Phase 2, melanocytic lesions with peripheral globules were included between 2020 and 2023. In this phase, a predictive model was fitted to the dataset to evaluate the algorithm accuracy and ROC curve. In a second moment, 04 observers evaluated the dermoscopic images using the proposed algorithm, making it possible to estimate its performance. Results: Phase 1, of the 401 lesions, 179 were excised, 41 of which were melanomas. Melanomas were more common when located on the lower limbs (p<0.1) and presented a disorganized dermoscopic pattern. While melanocytic nevi were more common on the trunk and with an organized pattern. In addition, the presence of one of the following structures: atypical dots and globules, atypical vessels or blotch was associated with melanoma. Phase 2, the 55 lesions collected were excised and added to the final database (n= 456), based on the predicted values from this database, it was possible to establish a ROC curve whose area under the curve was 0.834 and accuracy was 71 .21%. Dermoscopic analysis by four observers demonstrated an area under the ROC curve of 0.627 to 0.765. Conclusion: Melanocytic lesions with peripheral globules are the greatest risk of melanoma in individuals older than 30 years if located on the lower limbs and if lesions reveal one or more of the following structures: atypical dots and globules, atypical vessels, or blotch. These characteristics found were validated by a predictive model demonstrating an excellent performance index through ROC curve analysis and an accuracy index within expectations

Pseudomelanomas at a referral ocular oncology center in Brazil / Pseudomelanomas em um centro de referência em oncologia ocular no Brasil

ABSTRACT Objective: To evaluate the epidemiological, clinical, and imaging profile of lesions that mimic choroidal melanoma. Methods: Retrospective study of medical records of suspected choroidal melanoma lesions referred to the Ocular Oncology Service from the Universidade Federal de São Paulo, from 2014 to 2020. Demographic data, clinical history, and exams were evaluated. Results: A total of 104 patients (mean age: 65.57 ± 13.18; 49.04% female) were referred to our service with suspected choroidal melanoma. Of these, 32 (30.77%) were classified as pseudomelanoma, while 72 (69.23%) had a confirmed diagnosis of choroidal melanoma. Pseudomelanoma cases manifested in older individuals (p < 0.001), with smaller lesions in height (p < 0.001), anteroposterior diameter (p = 0.008), and lateral diameter (p = 0.003) on ultrasound. Pseudomelanoma cases were associated with higher frequencies of vitreous hemorrhage (p = 0.014) and lower rates of the presence of a mass (p = 0.001) and retinal detachment (p < 0.001). The main diagnoses of pseudomelanoma cases were choroidal nevus (40.63%), subretinal hemorrhage (18.75%) and choroidal neovascular membrane (18.75%). Conclusion: Almost one third of the cases referred with suspected choroidal melanoma were pseudomelanomas, which demonstrates that there is still a considerable path to improve the ability of general ophthalmologists to clinically discriminate melanoma from other conditions that can mimic it.

RESUMO Objetivo: Avaliar a frequência e o perfil epidemiológico, clínico e de imagem das lesões que simulam o melanoma de coroide. Métodos: Trata-se de estudo de revisão retrospectiva de prontuários de suspeita de lesões de melanoma de coroide de 2014 a 2020 no Setor de Oncologia Ocular da Universidade Federal de São Paulo. Foram avaliados dados demográficos, dados clínicos e exames complementares. Resultados: Um total de 104 pacientes (média de idade: 65,57 ± 13,18; 49,04% do sexo feminino) foram encaminhados ao nosso serviço com suspeita de melanoma de coroide. Destes, 32 (30,77%) foram classificados como pseudomelanoma, enquanto 72 (69,23%) tiveram diagnóstico confirmado de melanoma de coroide. Os casos de pseudomelanoma manifestaram-se em indivíduos mais velhos (p < 0,001) e apresentaram lesões menores em altura (p < 0,001), diâmetro anteroposterior (p = 0,008) e diâmetro lateral (p = 0,003) na ultrassonografia. Os casos de pseudomelanoma estão associados a maiores frequências de hemorragia vítrea (p = 0,014) e menores taxas de presença de massa (p = 0,001) e descolamento de retina (p < 0,001). Os principais diagnósticos dos casos de pseudomelanoma foram nevo (40,63%), hemorragia sub-retiniana (18,75%) e membrana neovascular coroidal (18,75%). Conclusão: Quase um terço dos casos encaminhados com suspeita de melanoma de coroide foram pseudomelanomas, o que demonstra que ainda há um caminho considerável para melhorar a habilidade do oftalmologista geral em discriminar clinicamente o melanoma de outras condições que o simulam.

Primary Anorectal Melanoma: Case Report and Review of a Rare Neoplasm

Primary anorectal melanoma is a rare malignant melanocytic neoplasm; its principal manifestation is rectal bleeding. It has an ominous prognosis with a five-year survival rate of 10%. The case of a 56-year-old woman with rectal bleeding and the sensation of a rectal mass is presented. A polypoid lesion, resected transanally, was documented in the distal rectum during the colonoscopy. The histological study confirmed a primary anorectal melanoma.

El melanoma anorrectal primario es una neoplasia melanocítica maligna poco frecuente, su principal manifestación es el sangrado rectal. Tiene un pronóstico ominoso con una tasa de sobrevida del 10% a 5 años. Se presenta el caso de una mujer de 56 años con rectorragia y sensación de masa rectal. Durante la colonoscopia se documentó una lesión polipoide en el recto distal, que se resecó por vía transanal. El estudio histológico confirmó la presencia de un melanoma anorrectal primario.

Retalho plantar medial para reconstrução de defeitos em calcanhar após ressecção de melanoma lentiginoso acral: Uma série de 7 casos / Medial plantar flap for reconstruction of heel defects after resection of acral lentiginous melanoma: A series of seven cases

Introdução: A reconstrução da região plantar ainda é um dos grandes desafios da cirurgia plástica reconstrutiva. Os tecidos dessa região apresentam características únicas e que são essenciais para a manutenção da funcionalidade do membro. De toda a região plantar, a região do calcanhar é a área de maior sustentação do peso e submetida ao maior impacto. O retalho fasciocutâneo plantar medial é uma das opções reconstrutivas, pois representa tecido semelhante e mantém a sensibilidade para a área receptora. Método: Foi realizado um estudo retrospectivo através da coleta de dados de prontuário de pacientes que realizaram reconstruções da região do calcanhar com retalho plantar medial, no período de julho de 2013 a setembro de 2019. O estudo foi aprovado pelo Comitê de Ética para Análise de Projetos de Pesquisa do HCFMUSP (Número CAAE: 56849422.0.0000.0068). Resultados: A reconstrução de calcanhar após ressecção de melanoma lentiginoso acral foi realizada em 7 pacientes. Complicações cirúrgicas foram observadas em 3 pacientes, sendo que todos eles tinham idade acima de 50 anos e/ou alguma comorbidade associada. Houve 57,1% de complicações, sendo 37,5% relacionadas ao retalho e 12,5% relacionadas à área doadora. Ocorreram 3 necroses totais de retalho (42,9%) e 1 perda total de enxerto na área doadora (14,3%). Conclusão: O retalho plantar medial se apresenta como uma boa alternativa para a realização de reconstruções oncológicas de defeitos na região plantar do pé. Contudo, deve-se ponderar a escolha do paciente ideal e lembrar que a dissecção do seu pedículo vascular não é de fácil execução.

Introduction: Resurfacing the sole is still one of the great challenges of reconstructive plastic surgery. The tissues on the sole of the foot have unique characteristics essential for maintaining the limbs functionality. The heel has the most significant weight support and is subjected to the entire soles greatest impact. The medial plantar artery flap is one of the reconstructive options, as it represents similar tissue and maintains sensitivity to the recipient area. Methods: A retrospective study was performed by collecting data from medical records of patients who underwent reconstructions of the heel with a medial plantar artery flap from July 2013 to September 2019. The study was approved by the Ethics Committee for Analysis of Research Projects of HCFMUSP (CAAE number: 56849422.0.0000.0068). Results: Heel reconstruction was performed in 7 patients after acral lentiginous melanoma excision. Surgical complications were observed in 3 patients, all of whom were aged over 50 years or have associated comorbidity. There were 57.1% of complications, 37.5% related to the flap, and 12.5% related to the donor area. There were three total flap necroses (42.9%) and one total graft loss in the donor area (14.3%). Conclusion: The medial plantar flap presents itself as a good alternative for performing oncological reconstructions of defects in the plantar region of the foot. However, the choice of the ideal patient should be considered and we must remember that the dissection of its vascular pedicle is not easily executed.

Caso infrecuente de melanoma del canal anal / Rare case of melanoma of the anal canal

Introducción: El melanoma anorrectal es un tumor infrecuente que se caracteriza por ser agresivo y de mal pronóstico; constituye el 1 por ciento entre los tumores malignos colorrectales. Es más frecuente en pacientes femeninas de más de 50 años y alcanza un pico máximo en la octava década de la vida. Objetivo: Presentar las características clínicas de una paciente con melanoma del canal anorrectal. Caso clínico: Se estudió a una paciente femenina de 61 años que acudió a consulta de gastroenterología, por presentar constipación de varios meses de evolución, asociada a tenesmo rectal, anorexia, astenia y pérdida de peso de forma rápida y progresiva. Se le diagnosticó un melanoma anorrectal, en estado avanzado de la enfermedad, por lo que tuvo mala evolución. Conclusiones: Con una anamnesis y exploración física minuciosa, asociado al uso de los medios diagnósticos disponibles y un elevado índice de sospecha, se consigue con la paciente, que el estudio y diagnóstico se hicieran con prontitud y con ello imponer tratamiento(AU)

Introduction: Anorectal melanoma is an infrequent tumor characterized by aggressive and poor prognosis; it constitutes 1 percent among colorectal malignancies. It is more frequent in female patients over 50 years of age and reaches a maximum peak in the eighth decade of life. Objective: To present the clinical characteristics of a patient with melanoma of the anorectal canal. Clinical case: A 61-year-old female patient was studied, who came to the gastroenterology department for constipation of several months of evolution, associated with rectal tenesmus, anorexia, asthenia and rapid and progressive weight loss. He was diagnosed with anorectal melanoma, in advanced stage of the disease, for which he had poor evolution. Conclusions: With a thorough anamnesis and physical examination, associated with the use of the available diagnostic means and a high index of suspicion, it is achieved with the patient, that the study and diagnosis were made promptly and thus impose treatment(AU)

Current management of patients with cutaneous melanoma with a positive sentinel lymph node / Tratamiento actual de pacientes con melanoma cutáneo y ganglio centinela positivo

Abstract Introduction : Immediate completion lymph node dissection (CLND) performed in patients with a positive sentinel lymph node biopsy (SLNB) cutaneous melanoma is not associated with improved melanoma specific survival versus active surveillance (AS) using nodal ul trasound. Clinical practice experience and outcomes of AS and adjuvant therapy is now starting to be published in literature. Methods : Retrospective analysis of patients with a positive-SLNB between June/2017-February/2022. Impact of management on any-site recurrence free survival (RFS), isolated nodal recurrence (INR), distant metasta sis-free survival (DMFS) and melanoma-specific survival (MSS) was evaluated. Results : From 126 SLNB, 31 (24.6%) were positive: 24 received AS and 7 CLND. Twenty-one (68%) received ad juvant therapy (AS, 67% and CLND, 71%). With a median follow-up of 18 months, 10 patients developed recur rent disease with an estimated 2-yr RFS of 73% (CI95%, 0.55-0.86) (30% in AS group vs. 43% in dissection group; P = 0.65). Four died of melanoma with an estimated 2-yr MSS of 82% (CI 95%, 0.63-0.92) and no differences between AS and CLND groups (P = 0.21). Estimated 2-yr DMFS of the whole cohort was 76% (CI 95%, 0.57-0.88) with no differences between groups (P = 0.33). Conclusion : Active surveillance strategy has been adopted for most positive-SLNB cutaneous melanoma patients. Adjuvant therapy without immediate CLND was delivered in nearly 70% of patients. Our results align with outcomes of randomized control trials and previous real-world data.

Resumen Introducción : La linfadenectomía inmediata (LI) re alizada en pacientes con biopsia de ganglio centinela (BGC) positivo por melanoma cutáneo no está asociada a mejoría en la supervivencia libre de enfermedad vs. vigilancia activa (VA). Resultados oncológicos y experi encia en la práctica clínica con dicha conducta asociados a tratamiento adyuvante comienzan a ser publicados en la literatura. Métodos : Análisis retrospectivo incluyendo paci entes con BGC-positiva por melanoma cutáneo entre junio/2017-febrero/2022. Se evaluó impacto del manejo en: supervivencia libre de recurrencia (SLR), recurren cia ganglionar aislada (RGA), supervivencia libre de metástasis a distancia (SLMD) y supervivencia libre de enfermedad (SLE). Resultados : De 126 pacientes, 31 (24.6%) fueron positi vos: en 24 se realizó VA y en 7 LI. Veintiún pacientes (68%) recibieron tratamiento adyuvante (VA, 67% y LI, 71%). Con una media de seguimiento de 18 meses, 10 pacientes presentaron recurrencia de la enfermedad con una SLR estimada a 2 años del 73% (CI95%, 0.55-0.86) (30% en VA vs. 43% en LI; P = 0.65). Cuatro murieron de melanoma con una SLE a 2 años del 82% (CI 95%, 0.63-0.92); sin diferencia entre ambos grupos (P = 0.21). La SLMD a 2 años de toda la cohorte fue de 76% (CI 95%, 0.57-0.88; P = 0.33). Conclusión : La vigilancia activa se ha adoptado como conducta para la mayoría de los pacientes con BGC-positivo. El tratamiento adyuvante sin linfadenectomía inmediata se realizó en cerca del 70% de nuestra serie. Los resultados de nuestra serie son similares a los re portados en la literatura.

Clinical and imaging research in the diagnosis of anorectal melanoma with surgical outcome: a case report and literature review

Objective: This study aims to report the case of a 69-year-old female patient with a diagnosis of anorectal melanoma (AM) established by immunohistochemistry. Methods: Clinical case report, a descriptive and qualitative study. Results: The patient had a nodular and ulcerative lesion in the anal region, the imaging exams revealed an expansive lesion that affected the rectum and the vaginal wall. The chosen course of treatment was initial surgical intervention, the surgery and postoperative course progressed without complications, and the anatomopathological examination confirmed the diagnosis of invasive malignant melanoma of the distal rectum of anorectal transition. The anatomopathological examination confirmed the diagnosis of invasive malignant melanoma located in the distal rectum of the anorectal transition. Immunohistochemistry analysis showed infiltrative melanoma with microsatellites, as well as peri and intratumoral lymphocytic infiltrate, angiolymphatic invasion, and perineural invasion. The surgical resection margins, ovaries, posterior vaginal wall, and parametrium showed no signs of neoplastic involvement. Following the surgery, the patient began immunotherapy, which she is still undergoing. Conclusions: The survival rate of AM can be improved through various diagnostic and therapeutic modalities. However, further exploration of this topic through clinical studies is necessary to enhance both diagnosis and treatment. (AU)

Máculas melanóticas del pene. Presentación de un caso

Las máculas melanóticas del pene son lesiones idiopáticas, benignas, poco frecuentes, en ocasiones multifocales, heterocrómicas e irregulares, que deben diferenciarse del melanoma de mucosas. Se presenta el caso de un paciente con lesiones pigmentadas en el pene, asintomáticas, pero que se habían incrementado en número. Con la ayuda de la dermatoscopia y la histopatología, se llegó al diagnóstico de máculas melanóticas del pene. Aunque son reducidas las opciones terapéuticas en el medio descrito, la trascendencia del diagnóstico de esta dermatosis radica en descartar la posibilidad de su malignidad.

Melanotic macules of the penis are idiopathic, benign, rare lesions, sometimes multifocal, heterochromic and irregular, which must be differentiated from mucosal melanoma. A patient with asymptomatic pigmented lesions on the penis, but which had increased in number is presented. With dermoscopy and histopathology test, the diagnosis of melanotic macules of the penis was reached. Although the therapeutic options in the described environment are limited, the significance of this dermatosis diagnosis lies in ruling out the possibility of its malignancy.