Correlation of histopathological patterns in cutaneous melanoma with BRAF mutations / Correlação de padrões histopatológicos de melanomas cutâneos com mutações BRAF

INTRODUCTION: Mutations on BRAF gene located on chromosome 7q are the most frequently found in cutaneous melanomas (60 percent-80 percent). The only study correlating histopathological patterns of cutaneous melanomas with the presence of BRAF mutations was undertaken by Viros et al. in 2008. The authors observed that morphological features of melanomas are associated with BRAF mutations. OBJECTIVES: To correlate histopathological patterns in cutaneous melanoma with the presence of BRAF mutations in order to corroborate the results of the study performed by Viros et al. METHODS: Paraffin embedded surgical specimens of 20 primary cutaneous melanomas with BRAF mutation and 20 specimens without BRAF mutation were evaluated independently by two dermatologists that carried out a blind experiment. The features analyzed were nesting, circumscription, presence of isolated melanocytes in the lesion, size and shape of neoplastic cells, and tumor cell pigmentation. RESULTS: "Nesting" was the most prevalent variable for the determination of melanomas with BRAF mutations according to both observers (r = 0.46; p = 0.04). CONCLUSION: As far as mutational status is concerned, it was not possible to confirm any predictive value for histopathological patterns such as circumscription, presence of isolated melanocytes in the lesion and cytological features. Difficulties in the interpretation of some histological criteria were demonstrated by the variation in the observers' conclusions. It is difficult to state if genetic alterations such as BRAF mutations may serve as biomarkers for melanoma classification.

INTRODUÇÃO: Mutações do gene BRAF localizado no cromossomo 7q são as mais frequentemente encontradas em melanomas cutâneos (60 por cento-80 por cento). O único estudo que correlacionou padrões histopatológicos de melanomas cutâneos com a presença de mutações BRAF foi realizado por Viros et al., em 2008, que observaram que características morfológicas de melanomas estavam associadas a mutações BRAF. OBJETIVOS: Correlacionar padrões histopatológicos de melanomas cutâneos com a presença de mutações BRAF, a fim de confirmar os achados de Viros et al. MÉTODOS: Espécimes em parafina de 20 casos de melanomas cutâneos primários com mutações BRAF e 20 casos sem mutações foram avaliados independentemente por dois dermatologistas sem o conhecimento da presença ou não das mutações. Os padrões analisados foram formação de "ninhos", circunscrição, presença de melanócitos isolados na lesão, tamanho e forma das células neoplásicas e pigmentação das células tumorais. RESULTADOS: A formação de "ninhos" foi a variável com o maior poder de determinação para melanomas com mutações BRAF para ambos os observadores (r = 0,46; p = 0,04). CONCLUSÃO: Não foi possível confirmar nenhum valor preditivo em relação ao status mutacional de um melanoma para os padrões histológicos circunscrição e presença de melanócitos isolados na lesão, bem como para características citológicas. Dificuldades na interpretação de alguns critérios histológicos foram demonstradas pela variação da concordância entre os observadores. É difícil afirmar se alterações genéticas como as mutações BRAF podem servir como biomarcadores para a classificação de melanomas.

Urotelio versus mucosa intestinal en ampliación vesical con sigmoide desmucosado: resultados de histopatología de largo plazo / Comparison between intestinal mucosa and urothelium in the setting of bladder augmentation: long term results

La ampliación vesical (AV) con sigmoide desmucosado ha mostrado grandes beneficio como reducción del mucus urinario y sus complicaciones. El objetivo de este estudio es determinar los cambios histológicos que acompañan a esta observación clínica, evaluando las transformaciones del epitelio de revestimiento del parche implantado; en distintos periodos post ampliación. Métodos: En 35 pacientes operados de AV (1998-2005), se realizaron aleatoriamente 24 exámenes endoscópicos con sus respectivas biopsias. La biopsia se tomó en tres puntos distintos del parche de ampliación desmucosado (9-12 y 3hrs). En aquellos niños con cierre de cuello, se utilizó un trocar trans-vesical. Los resultados histopatológicos (HP) se compararon entre diferentes períodos, con mucosa intestinal normal y con 2 biopsias realizadas sin parche desmucosado (>10 años). Resultados: La edad promedio al momento de la biopsia fue de 12 años (rango 4 a 15). El periodo de toma de biopsia tiene una mediana de 39 meses (rango 12-84 meses) post ampliación. La descripción macroscópica mostró dos grupos; en el periodo menor a 3 años el intestino se ve recubierto con urotelio con algunas zonas de mucosa intestinal (“estrellado”), y en muestras mayores a 3 años el parche estaba completamente cubierto con mucosa intestinal pero más pálido. La HP de las biopsias efectuadas precozmente (< 36 meses) demostraron que el implante presenta mayoritariamente urotelio con pequeñas “estrellas” de mucosa sigmoidea normal con algunas glándulas atróficas. En la totalidad de las muestras > 36 meses se informó parche recubierto mayoritariamente con mucosa sigmoidea con glándulas rodeadas por tejido fibroso, mayoritariamente atróficas y ausencia de urotelio. En los 2 pacientes con ampliación vesical sin parche desmucosado las glándulas intestinales mostraron estructura normal. Conclusión: Podría plantearse la existencia de un fenómeno de regeneración y expansión de mucosa histológicamente...

Bladder augmentation (BA) using demucosalized sigmoid has showed excellent benefices as mucus reduction and its complications. The aim of this study is to determinate the histological changes of this clinical observation, evaluating the coating epithelium of the patch in different periods postaugmentation. Methods: There were 24 random endoscopies exams and biopsies performed in 35 cases who underwent a BA between 1998 and 2005. Biopsy was done in 3 different points of the augmentedpatch (9-12-3 o’clock). In those children with bladder neck surgery a trans-vesical trocar was used. Histopathology (HP) results were compared among different post augmented periods, with normal intestinal mucosa and with biopsies done in 2 cases of BA where sigmoid without demucosalized was used (>10 years). Results: The mean age at biopsy was 12 years (range 4-15 y) and the period of biopsy has a median post BA of 39 months (range 12-84 m). Macroscopic description showed 2 groups; one (< 3 years) where the intestine was covered by urothelium with some small areas of intestinal mucosa (“stars”), and the other over 3 years where the patch was covered completely with intestinal mucosa. HP results in the early biopsies (< 36 months) showed that the patch was mostly covered with urothelium with some small “stars” of sigmoid mucosa, but with atrophic glands. In the group > 36 months the patch was mostly covered with intestinal mucosa with atrophic glands surrounded by fibrotic tissue and no signs of urothelium. In the 2 cases of BA with sigmoid without demucosalized the intestinal glands were completely normal. Conclusion: It could be affirmed that there is a regenerative and expansive process of mucosa histologically similar to a normal sigmoid mucosa (< 3 years), which could begin from intestinal mucosa remnants (“stars”). While the glandular structure would be atrophic in the patch, it was normal in those cases augmented with sigmoid without...