Tongue metastasis of cutaneous melanoma : report of two cases and literature review

Malignant metastases to the oral cavity are rare and metastatic melanomas of the tongue are considered exceptionally uncommon, with less than 10 cases published in the English literature so far. Two female patients in the 7th decade of life presented to our dental service with nodules in the tongue. Both patients had multiple metastases at the time of oral diagnosis and primary melanoma originated on the skin. An intra-oral incisional biopsy was performed under local anesthesia and the histopathologic analysis was characterized by the proliferation of atypical epithelioid cells displaying a poorly delimited cytoplasm and hyperchromatic nucleus which contained eosinophilic macronucleoli. Immunohistochemistry was performed in both cases to confirm the clinical hypothesis of metastatic melanoma. After the diagnosis of oral metastatic melanoma, the patients were maintained under palliative care and close medical follow-up. Both patients died four and a half months and 20 months after the diagnosis of tongue metastasis. Although rare, metastatic melanoma should be included in the differential diagnosis of tongue lesions detected in patients with a previous medical history of cutaneous melanoma

Effects of Mimosa caesalpiniifolia pre-formulation on the intestinal barrier during sodium dextran sulfate-induced colitis in Wistar rats

Introduction. Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats. Objective. To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model. Materials and methods. Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses. Stool samples were collected and processed for analysis of the short-chain fatty acid. Results. Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation. Conclusions. The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier

Pathological response and immunohistochemical biomarkers in high risk localized prostate cancer treated with neoadjuvant therapy and radical prostatectomy

Introdução. A maioria dos casos de câncer de próstata (CaP) é diagnosticada na fase localizada da doença. Ao redor de 20% desses pacientes apresentam alto risco para progressão sistêmica. Esse subgrupo possui maior chance de recidiva bioquímica e maior mortalidade câncer-específica. O tratamento do câncer de próstata localizado de alto risco (CAPLAR) é primordialmente voltado ao controle local da doença e geralmente envolve a prostatectomia radical (PR). Evidências recentes apontam que o uso de terapia de deprivação androgênica intensa (TDA-I) antes da PR poderia elevar as chances de controle local no grupo CAPLAR. Nesse sentido, a busca por biomarcadores capazes de predizer a resposta patológica tem se tornado mais relevante. Objetivo. Avaliar resposta patológica e marcadores imuno-histoquímicos selecionados em indivíduos portadores de CaPLAR tratados com terapia anti-androgênica neoadjuvante (TDA-I) seguida de PR. Metodologia. O presente estudo foi realizado a partir de um ensaio clínico prospectivo voltado à verificação de eficácia e segurança de modalidades de TDA-I neoadjuvante em portadores de CAPLAR elegíveis à prostatectomia radical. Nesse contexto, abordamos a expressão imuno-histoquímica de marcadores selecionados (PTEN, ERG, AR, AR-V7, Glico-R, PSMA, NKX3.1, p53 e Ki67) em biópsias de próstata por agulha. Em seguida, analisamos os resultados pré e pós-tratamento a fim de buscar associações dos parâmetros clínicos, histopatológicos e imuno-histoquímicos com a resposta patológica encontrada no espécime cirúrgico e com a recidiva bioquímica após trinta meses de seguimento. Resultados. Sessenta e dois indivíduos atingiram a etapa cirúrgica do estudo. A taxa global de resposta patológica satisfatória (RCB<0,25 cm³) foi de 22,5% (14/62). Indivíduos com perfil imuno-histoquímico desfavorável (PTEN-deficiente ou ERG-positivo) pré-tratamento (38,7%) exibiram maior quantidade de tumor residual no espécime cirúrgico. Esse perfil mostrou estar associado ao grupo racial branco. A taxa de recorrência bioquímica foi de 48,3% após trinta meses de seguimento. Houve associação significativa entre os grupos de resposta patológica e o intervalo livre de recorrência bioquímica. Na análise multivariada, a carga tumoral foi o melhor preditor pré-tratamento de sucesso terapêutico enquanto que o acometimento linfonodal foi o mehor preditor pós-tratamento de recorrência bioquímica. Conclusões. A neoadjuvância no cenário de CAPLAR é um recurso seguro e inovador que, para um subgrupo selecionado de indivíduos com menor carga tumoral inicial e perfil imuno-histoquímico favorável (PTEN-preservado e ERG-negativo), pode exercer um papel terapêutico complementar ao da cirurgia a fim de otimizar o controle localIntroduction. Currently prostate cancer is mostly detected in localized stages. Twenty percent of patients present high risk of sistemic progression. This subgroup shows higher chance of biochemical recurrence and cancer-specific mortality. High risk localized prostate cancer (HRLPC) treatment is primarily focused on local disease control and usually requires radical prostatectomy. In spite of the best local treatment, almost half of the patients will progress along their lifetime. Recent evidences point that the use of intense androgenic deprivation therapy before surgery would increase disease free survival rates on HRLPC subgroup. Thereby, the search for new biomarkers to predict therapeutic response is turning more relevant. Objetive. Our aim is to study the pathological response and selected immunomarkers (PTEN, ERG, AR, AR-V7, Glico-R, PSMA, NKX3.1, p53 and Ki67) in HRLPC individuals ongoing a clinical trial based on neoadjuvant therapy followed by radical prostatectomy. Methods. This study is part of a prospective randomized controlled clinical trial which analyzes efficacy and safeness of neoadjuvant hormonal therapy modalities in HRLPC patients eligible for radical prostatectomy. In this context, we evaluated the immunohistochemical expression of selected markers in prostate needle biopsies. We then analyzed the pre and post-treatment results in order to search for clinical, histological and immunohistochemical associations with the pathological response found in the surgical specimen and with the biochemical recurrence after thirty months follow-up. Results. Sixty-two individuals reached the surgical stage of the study. The overall satisfactory pathologic response rate (RCB<0.25 cm³) was 22.5% (14/62). Individuals with an unfavorable immunohistochemical profile (PTEN-deficient or ERG-positive) in the pretreatment biopsy (38.7%) exhibited higher volume of residual tumor in the surgical specimen. This profile was also associated with the white racial group. The biochemical recurrence rate was 48.3% after thirty months of follow-up. There was a significant association between the pathologic response and the biochemical recurrence-free interval. The multivariate analysis showed that the lower pretreatment tumor burden was the best predictor of therapeutic success, while lymph node involvement and perineural invasion were the best predictors of biochemical recurrence. Conclusions. Neoadjuvant therapy in HRLPC is safe and innovative resource that might play a complementary therapeutic role to radical surgery in a selected subgroup of patients with low initial cancer burden and a favorable immunohistochemical profile (PTEN-preserved and ERG-negative

Avaliação Da Imunoexpressão De Bap1, Alk, Ros1 E P16 Em Neoplasias Melanocíticas Spitzoides

Introduction. Spitzoid tumors represent a heterogeneous group of melanocytic neoplasms. In recent years, several advances in Molecular Biology afforded significant discoveries on the pathogenesis and the biological behavior of these tumors. The BAP1 inactivation, the presence of kinase fusion related-proteins and the role of p16 protein are among the main criteria launched by new classification proposals and represent innovative markers with potential clinical significance. Objetive. To evaluate the immunohistochemical expression of BAP1, ALK, ROS1 and p16 proteins in spitzoid tumors. Methods. Retrospective study based on 47 tissue samples fixed in formalin and embedded in paraffin. This series was composed by the Pathology archives of three cancer reference institutions in the state of São Paulo, Brazil. Clinical-demographic data, histopathological aspects and immunohistochemical results for BAP1, ALK, ROS1 and p16 were studied in this case series composed by 27 Spitz nevus (NS), 15 Atypical Spitzoid Tumors (AST) and 5 Spitzoid Melanomas (MS). Results. Medium age was 21.2 years. Medium histological tumoral width was 5.7 millimeters. We observed statistical significance between diagnostic categories and age, width, mitotic index, ulceration, atypia, loss of maturation and the presence of giant cells. The global frequency of BAP1- inactivated tumors was 4.3% (02/46), both of them AST. The proportional frequency of BAP1-inactivated cases in AST group was 14.2% (02/14). We found no immunostaining for ALK and ROS1 in any out of 47 studied cases. We also did not observe a statistically significant correlation between loss of immunoexpression of p16 and non-benign categories. Conclusions. Age, width and mitotic index were significant diagnostic criteria to differentiate between MS and the remaining categories. Ulceration, atypia, loss of maturation and the presence of giant cells were significant diagnostic criteria to differentiate benign lesions (NS) and non-benignlesions (AST and MS). The loss of nuclear immunoexpression of BAP1 was exclusive to the AST category. We did not observe immunoexpression of ALK or ROS1 in any case. The immunohistochemical evaluation of p16 protein did not allowed differentiation between benign tumors (NS) and non-benign tumors (AST and MS).Introdução. Tumores spitzoides compõem um grupo heterogêneo de neoplasias melanocíticas. Nos últimos anos, avanços no campo da biologia molecular possibilitaram descobertas significativas sobre a patogênese e o comportamento biológico desses tumores. A inativação de BAP1, a presença de proteínas relacionadas a translocações em genes codificadores de tirosinoquinases e a função da proteína p16 estão dentre os critérios utilizados por novas propostas de classificação e representam marcadores com potencial significado clínico. Objetivo. Avaliar a expressão imuno-histoquímica das proteínas BAP1, ALK, ROS1 e p16 em tumores spitzoides. Metodologia. Estudo retrospectivo baseado em 47 amostras de tecido fixado em formol e incluído em parafina. A composição da casuística contou com a contribuição dos arquivos de três instituições de referência oncológica no estado de São Paulo, Brasil. Dados clínico-demográficos, aspectos histopatológicos e reatividade imuno-histoquímica para BAP1, ALK, ROS1 e p16 foram analisados em uma série composta por 27 nevos de Spitz (NS), 15 tumores spitzoides atípicos (AST) e 5 melanomas spitzoides (MS). Resultados. A média etária foi de 21,2 anos. O tamanho tumoral médio foi de 5,7 milímetros. Foi observada significância estatística entre as categorias diagnósticas e as variáveis idade, tamanho, índice mitótico, ulceração, atipia, perda de maturação e presença de células gigantes. A frequência geral de casos BAP1-inativados foi 4,3% (02/46), ambos pertencentes à categoria AST. A frequência proporcional de casos BAP1-inativados da categoria AST foi de 14,2% (02/14). Em relação aos anticorpos ALK e ROS1, não foi observada imunopositividade em nenhum dos 47 tumores spitzóides avaliáveis. Também não encontramos correlação significativa entre a perda de imunoexpressão de p16 e as categorias diagnósticas. Conclusões. Idade, tamanho e índice mitótico foram critérios diagnósticos significativos para a diferenciação entre MS e as demais categorias. Ulceração, atipia, perda de maturação e presença de células gigantes foram critérios diagnósticos significativos para a diferenciação entre lesões benignas (NS) e lesão não-benignas (AST e MS). A perda de imunoexpressão nuclear de BAP1 foi exclusiva à categoria AST. Não houve imunoexpressão de ALK ou ROS1 xiii em nenhum caso estudado. A avaliação imuno-histoquímica de p16 não permitiu diferenciar tumores benignos (NS) de tumores não-benignos (AST e MS).Dados abertos - Sucupira - Teses e dissertações (2017

Sclerosing TSC1 mutated renal cell carcinoma: An unusual pattern mimicking MITF family translocation renal cell carcinoma

The tuberous sclerosis genes and MTOR are increasingly being found to have important roles in novel subtypes of renal cancer, particularly emerging entities eosinophilic solid and cystic renal cell carcinoma (RCC) and high-grade oncocytic renal tumor (HOT)/RCC with eosinophilic and vacuolated cytoplasm. We report a unique renal neoplasm in a 66-year-old woman that initially mimicked MITF family translocation RCC due to mixed clear and eosinophilic cells, extensive stromal hyalinization, and psammoma bodies, yet which was negative for TFE3 and TFEB fluorescence in situ hybridization and a next generation sequencing (NGS) gene fusion assay. Cytoplasmic stippling triggered consideration of TSC-associated neoplasms, and a targeted NGS assay revealed a variant in exon 21 of TSC1 resulting in c.2626G\u3eT p.(Glu876*) truncating mutation. This report adds to the morphologic spectrum of TSC-related renal neoplasms, including prominent stromal hyalinization as a potentially deceptive pattern. Due to the overlap in cytoplasmic stippling between eosinophilic solid and cystic RCC and HOT/RCC with eosinophilic and vacuolated cytoplasm, it is debatable which category this example would best fit. Further understanding of these entities and other renal neoplasms with alterations in the TSC genes will elucidate whether they should be considered a family of tumors

Acquired cystic kidney disease in allograft with long-standing poor function

Abstract Acquired Cystic Kidney Disease (ACKD) is regarded as a common late condition of end stage renal damage and expresses its most important features when associated with long term hemodialysis. ACKD is also widely known as a premalignant lesion. Its occurrence in chronically rejected renal allografts is rare and its frequency and behavior in this setting are not well known. Herein we report a case of ACKD in a long standing nonfunctional allograft (215 months) which is not associated with malignancy and briefly review the related literature

Supplementary_table – Supplemental material for Immunoexpression of BAP1, ROS1, and ALK in Spitzoid Melanocytic Tumors

<p>Supplemental material, Supplementary_table for Immunoexpression of BAP1, ROS1, and ALK in Spitzoid Melanocytic Tumors by Leonardo Cardili, Cristiano Ribeiro Viana, Andressa Germano, Mariana Fernandes, Denise Barcellos and Gilles Landman in International Journal of Surgical Pathology</p