BRAF-Mutated Melanoma Journey in Latin America: Expert Recommendations From Diagnosis to Treatment.

OBJECTIVES: • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region. INTRODUCTION: Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region's incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region. METHODS: Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment. RESULTS AND CONCLUSIONS: Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.

Intraoperative assessment of surgical margins using ‟en face" frozen sections in the management of cutaneous carcinomas

Abstract Background: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative ‟en face" freezing technique evaluates all peripheral and deep margins. Objective: To report the results of the ‟en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. Methods: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. Results: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative ‟en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. Study limitations: Not having a minimum follow-up time of 5 years for all patients. Conclusion: The ‟en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Melanoacanthoma: a potential pitfall of reflectance confocal microscopy.

Melanoacanthoma is a rare variant of seborrheic keratosis, which is notable for dark pigmentation and fast radial growth, making it difficult to distinguish from melanoma. Histologically, it is characterized by proliferation of keratinocytes and dendritic melanocytes. The authors report a scalp lesion, fast growing, suspected by dermoscopy and confocal microscopy examination, with dendritic cells distributed throughout the lesion. Based on these findings, it was not possible to classify this lesion as clearly benign, so it was excised. Histopathologic evaluation and immunostain were consistent with melanoacanthoma.

Melanoacanthoma: a potential pitfall of reflectance confocal microscopy

Abstract Melanoacanthoma is a rare variant of seborrheic keratosis, which is notable for dark pigmentation and fast radial growth, making it difficult to distinguish from melanoma. Histologically, it is characterized by proliferation of keratinocytes and dendritic melanocytes. The authors report a scalp lesion, fast growing, suspected by dermoscopy and confocal microscopy examination, with dendritic cells distributed throughout the lesion. Based on these findings, it was not possible to classify this lesion as clearly benign, so it was excised. Histopathologic evaluation and immunostain were consistent with melanoacanthoma.

Proliferating trichilemmal cyst with clinical, radiological, macroscopic, and microscopic correlation.

Proliferating trichilemmal cyst is an uncommon neoplasm arising from the follicular isthmus, whose histopathological hallmark is the presence of trichilemmal keratinization. We describe a case of proliferating trichilemmal cyst in a 57-year-old woman with a broad clinical, radiological, macroscopic and microscopic correlation.

Proliferating trichilemmal cyst with clinical, radiological, macroscopic, and microscopic correlation

Abstract: Proliferating trichilemmal cyst is an uncommon neoplasm arising from the follicular isthmus, whose histopathological hallmark is the presence of trichilemmal keratinization. We describe a case of proliferating trichilemmal cyst in a 57-year-old woman with a broad clinical, radiological, macroscopic and microscopic correlation.

Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience.

Diphencyprone has been reported as a local immunotherapy for cutaneous melanoma metastases. We aim to report cases of melanoma patients treated with diphencyprone in a single Brazilian institution and highlight their outcomes. Since 2012, we have treated 16 melanoma patients with cutaneous metastases with topical diphencyprone. To date, we have had 37.5% of complete response, 25% of partial responses, and 31.25% patients without any response. Treatment was well tolerated and local toxicity was easily controlled. We believe topical diphencyprone is a feasible treatment that can be another option for treating melanoma patients, especially in cases of in-transit or extensive disease.

Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience

Abstract: Diphencyprone has been reported as a local immunotherapy for cutaneous melanoma metastases. We aim to report cases of melanoma patients treated with diphencyprone in a single Brazilian institution and highlight their outcomes. Since 2012, we have treated 16 melanoma patients with cutaneous metastases with topical diphencyprone. To date, we have had 37.5% of complete response, 25% of partial responses, and 31.25% patients without any response. Treatment was well tolerated and local toxicity was easily controlled. We believe topical diphencyprone is a feasible treatment that can be another option for treating melanoma patients, especially in cases of in-transit or extensive disease.

Metastatic area ratio can help predict nonsentinel node positivity in melanoma patients.

Several studies suggest that melanoma patients with a positive sentinel node biopsy (SNB) can avoid having complete nodal dissection on the basis of pathological features of the node. The aim of the study was to determine the value of metastatic area ratio as a predictive factor for nonsentinel node (NSN) positivity. A retrospective analysis was carried out of melanoma patients who underwent SNB in a single institution between 2000 and 2010. A total of 697 patients were evaluated. In 155 patients (22.2%), the SNB was positive; 146 lymphadenectomies were performed, and 23 patients in whom this was performed (15.8%) had positive NSN. In multivariate analyses, Breslow thickness of more than 2 mm, perinodal vascular invasion, and metastatic area ratio were significantly related to NSN positivity in the complete nodal dissection. Metastatic area ratio of a positive SNB can be valuable in predicting the risk of NSN positivity.

Vemurafenib and cutaneous adverse events - report of five cases

Vemurafenib is a selective inhibitor of V600E-mutant BRAF protein used to treat metastatic and unresectable melanoma. Clinical trials have shown increased overall survival and progression-free survival in patients treated with Vemurafenib. However, cutaneous adverse events are common during treatment. We report fi ve cases of metastatic melanoma with BRAF V600E positivity, treated with Vemurafenib and its cutaneous adverse events. Dermatologists and oncologists need to be aware of possible skin changes caused by this medication, which is increasingly employed in melanoma treatment. Monitoring of patients during therapy is important for early treatment of adverse cutaneous cutaneous adverse events, improvement in quality of life and adherence to treatment.

Análise da heterogeneidade do status mutacional do gene KRAS em carcinoma colorretal primário e metastático / Analysis of KRAS mutation heterogeneity in primary and metastatic colorectal cancer

Introdução: Mutações no gene KRAS são preditoras negativas de resposta ao tratamento com inibidores do Receptor do Fator de Crescimento Epidérmico (EGFR) em Carcinoma Colorretal (CCR) metastático. Questiona-se qual a melhor amostra tecidual para pesquisar a mutação deste gene. O objetivo desse estudo é avaliar a heterogeneidade do status mutacional do gene KRAS entre diferentes áreas do tumor primário e na metástase. Além disso, testar se a detecção das mutações mais frequentes de KRAS são reprodutíveis entre material parafinado e congelado, e ainda avaliar o impacto das porcentagens de células estromais não neoplásicas presentes na amostra tecidual selecionada para extração de DNA. Material e Métodos: DNA de material parafinado do tumor primário e dametastáse foi obtido de 102 pacientes. Mutações nos codons 12, 13 e 61 do gene KRAS foram avaliadas por pirosequenciamento. Para os experimentos comparativos entre material congelado e parafinado 31 casos parafinado com 5 diferentes mutações conhecidas de KRAS foram selecionados baseados na disponibilidade de tecido congelado. A quantificação de células tumorais foi realizada em diferentes áreas do tumor primário em 8 casos através da análise digital de imagens. Resultados: A população de estudo consistiu de 102 pacientes com CCR meta stático. DNA foi extraído de 2 áreas do tumor primário em 20 casos e 3 áreas em 71 casos...

Background: Mutations in KRAS are negative predictors of the response to anti-EGR therapies in the treatment of metastatic colorectal cancer. Question raises regarding the best tissue to test for KRAS mutation. The aim of this study is to test the heterogeneity of KRAS mutational status between different areas of the primary lesion and between paired primary CRC and corresponding metastasis. Another objective is to examine whether the frequently described types of KRAS mutations found in CRC are reproducible between formalin fixed-paraffin embedded tissue (FFPET) and frozen tissue (FT) using the pyrosequencing method, and additionally to test the impact of the percentage of tumor cells in the tissue sample regarding the quantification of the mutated allele. Design: DNA from two or three areas from the primary tumor and from one area of the metastatic tissue was obtained from FFPET from 102 metastatic CRC patients. KRAS codons 12, 13 and 61 mutations were analyzed by pyrosequencing. From frozen versus FFPET experiments, 31 previously sequenced FFPE T cases presenting 5 different mutations KRAS gene were selected based on the availability of paired frozen tissue in A.C.Camargo Center Biobank. Quantification of percentage of tumor cell was performed in different areas of the primary tumor in 8 cases by digital analysis. Results: The study population consisted of 102 metastatic CRC patients. DNA extracted from 2 areas in 20 cases and 3 areas in 71 cases. Only one of the patients showed intratumor heterogeneity and it was regarding KRAS mutation type (one area showed c.35G>T and the other two areas c.35G>A). From this patient, both LN and liver metastasis presented with the c.35G>T mutation. We tested 97 of the patients for heterogeneity regarding paired primary and metastatic tissue, and we found heterogeneity in 2 cases (2,1%)...

Tomografia de coerência óptica no diagnóstico do carcinoma basocelular / Optical coherence tomography in the diagnosis of basal cell carcinoma

O diagnóstico precoce do carcinoma basocelular, neoplasia cutânea de alta incidência, pode trazer grandes benefícios ao paciente. Muitas vezes lesões pouco pigmentadas, lesões iniciais pequenas e lesões superficiais podem representar um desafio diagnóstico clínico e dermatoscópico por não apresentar os achados típicos dessa neoplasia. Nessa situação, a tomografia de coerência óptica, tecnologia promissora na dermatologia, é recurso auxiliar não invasivo que pode ser incorporado à prática clínica.

Early diagnosis of basal cell carcinoma-a cutaneous neoplasia with high incidence-can bring great benefits to the patient. Often, slightly pigmented lesions, small initial lesions, and superficial lesions can represent a clinical and dermoscopic diagnostic challenge for not having the typical findings of this neoplasia. In such cases, optical coherence tomography-a promising technology in dermatology-is an auxiliary, non-invasive resource that can be incorporated into the clinical practice.