Abstract Introduction Colorectal carcinoma (CRC) is the most common gastrointestinal neoplasm in the world, accounting for 15% of cancer-related deaths. This condition is related to different molecular pathways, among them the recently described serrated pathway, whose characteristic entities, serrated lesions, have undergone important changes in their names and diagnostic criteria in the past thirty years. The multiplicity of denominations and criteria over the last years may be responsible for the low interobserver concordance (IOC) described in the literature. Objectives The present study aims to describe the evolution in classification of serrated lesions, based on the last three publications of theWorld Health Organization (WHO) and the reproducibility of these criteria by pathologists, based on the evaluation of the IOC. Methods A search was conducted in the PubMed, ResearchGate and Portal Capes databases, with the following terms: sessile serrated lesion; serrated lesions; serrated adenoma; interobserver concordance; andreproducibility.Articlespublished since 1990were researched. Results and Discussion The classification of serrated lesions in the past thirty years showed different denominations and diagnostic criteria. The reproducibility and IOC of these criteria in the literature, based on the kappa coefficient, varied in most studies, from very poor to moderate. Conclusions Interobserver concordance and the reproducibility of microscopic criteria may represent a limitation for the diagnosis andappropriatemanagementof these lesions. It is necessary to investigate diagnostic tools to improve the performance of the pathologist’s evaluation, for better concordance, and, consequently, adequate diagnosis and treatment.

RESUMO Introdução: A análise histológica de biópsias hepáticas pós-transplante pode trazer dificuldades na distinção entre hepatite crônica C (HCC) recorrente e outras causas de disfunção do enxerto, sobretudo rejeição celular aguda (RCA). Objetivo: Comparar as características histológicas de biópsias hepáticas de pacientes transplantados e não transplantados portadores de HCC, além de avaliar a presença de achados comuns à RCA. Métodos: Foram estudadas 40 biópsias de pacientes não transplantados e 30 de transplantados, de acordo com o escore de Ishak para grau de atividade necroinflamatória e estágio de fibrose. Foram ainda avaliadas as características do infiltrado inflamatório, da esteatose, das alterações ductais e da endotelite portal e da perivenulite central. Resultados: Em ambos os grupos, houve predomínio de leve grau de atividade necroinflamatória e leve fibrose. O infiltrado inflamatório portal também foi leve e predominantemente linfocítico em ambos os grupos. Alterações ductais foram mais frequentes em pacientes não transplantados. Esteatose também foi leve em ambos os grupos, mas predominou nos pacientes não transplantados. Endotelite portal ocorreu em 42,5% e 40% em HCC não transplantada e HCC pós-transplante, respectivamente. A frequência de endotelite centrolobular foi semelhante nos dois grupos. Conclusão: Os achados histológicos na HCC são semelhantes em pacientes transplantados e não transplantados. Além disso, características morfológicas da RCA estão presentes na HCC, tanto em fígados nativos como em enxertos de pacientes com infecção recorrente após transplante.

ABSTRACT Introduction: Histological analyses of post-transplant liver biopsies may be difficult in distinguishing recurrent chronic hepatitis C (CHC) from other causes of graft dysfunction, especially acute cellular rejection (ACR). Objective: The aim of this study was to compare the histological characteristics of liver biopsies with CHC in transplant and non-transplant patients with hepatitis C virus (HCV) infection and assess the occurrence of findings common to ACR. Methods: We studied 40 biopsies from non-transplant and 30 biopsies from post-transplant patients, according to the Ishak score for necroinflammatory activity grade and stage of fibrosis. We also assessed the inflammatory infiltrate, steatosis, ductal changes, portal endotheliitis and central perivenulitis. Results: We found predominance of mild grade and stage in both groups. The portal inflammatory infiltrate was also mild and mainly lymphocytic in the two groups. Ductal changes were more frequent in the non-transplant patients. Steatosis was also mild in both groups, but predominated in non-transplant CHC patients. Portal endotheliitis occurred in 42.5% and 40% in non-transplant and post-transplant CHC, respectively. The frequency of centrilobular endotheliitis was similar in both groups. Conclusion: Histological findings in chronic hepatitis C are similar in non-transplant and post-transplant patients. In addition, morphological features characteristic of ACR are also observed in HCV infection of native livers as well as in the graft of patients with recurrent infection after transplantation.

Introdução: O colangiocarcinoma é a segunda neoplasia maligna mais comum do sistema hepatobiliar. Durante a colangiocarcinogênese podem ocorrer alterações fenotípicas do epitélio ductal, incluindo a expressão de mucinas. Entretanto, os estudos que avaliam a expressão das mucinas nas diferentes etapas da colangiocarcinogênese são escassos. O CD56, apesar de contribuir na diferenciação entre as proliferações ductais benignas e o colangiocarcinoma, ainda não teve a sua expressão avaliada no epitélio displásico dos ductos biliares. Objetivos: Analisar o perfil das mucinas (MUC) 1, 2, 5, 6 e do CD56 no colangiocarcinoma, nas lesões pré-neoplásicas e reacionais de ductos biliares intra-hepáticos. Material e métodos: A expressão imuno-histoquímica da MUC 1, 2, 5, 6 e do CD56 foram avaliadas em 11 colangiocarcinomas e 83 ductos biliares intra-hepáticos (67 reativos e 16 displásicos). As variáveis foram consideradas como significativas quando p < 0,05. Resultados: A expressão da MUC1 ocorreu em cerca de 90% dos colangiocarcinomas, contrastando com a baixa frequência de casos positivos nos ductos biliares reativos ou displásicos (p < 0,001). Não houve diferença estatisticamente significativa na expressão de MUC5, MUC6 e CD56 entre as lesões reativas, displásicas e o colangiocarcinoma. O anticorpo anti-MUC2 foi negativo em todos os casos. Conclusão: A MUC1 contribuiu no diagnóstico diferencial entre o colangiocarcinoma e as lesões pré-neoplásicas e reacionais/regenerativas dos ductos biliares intra-hepáticos, e deve compor o painel de anticorpos a ser empregado visando o aprimorando destes diagnósticos diferenciais. Contrariamente, a MUC2, MUC5, MUC6 e o CD56 não se mostraram promissoras na diferenciação entre as diferentes etapas da colangiocarcinogênese.

Introduction: Cholangiocarcinoma is the second most common malignant neoplasm of the hepatobiliary system. During cholangiocarcinogenesis phenotypic changes occur in the ductal epithelium, including the expression of mucins (MUC). However, the evaluating studies of the expression of mucins in the different stages of cholangiocarcinogenesis are scarce. CD56 has also contributed in differentiating benign ductal proliferation and cholangiocarcinoma; however, its expression has not been evaluated in dysplastic epithelium of the bile duct yet. Objective: To assess immunohistochemical profile of (MUC) 1, 2, 5, 6, and CD56 in cholangiocarcinoma, pre-neoplastic and reactive lesions in the epithelium of intrahepatic bile ducts. Material and methods: Immunohistochemical expression of MUC 1, 2, 5, 6, and CD56 were studied for 11 cases of cholangiocarcinoma and 83 intrahepatic bile ducts (67 reactive and 16 dysplastic). Variables were considered significant when p < 0.05. Results: The expression of MUC1 occurred in about 90% of the cholangiocarcinomas, contrasting with the low frequency of positive cases in reactive and dysplastic bile ducts (p < 0.001). However, there was no statistically significant difference in the expression of MUC5, MUC6 and CD56 between the reactive or dysplastic lesions and cholangiocarcinoma. The anti-MUC2 antibody was negative in all cases. Conclusions: MUC1 contributed for the differential diagnosis between cholangiocarcinoma and pre-neoplastic and reactive/regenerative lesions of intrahepatic bile ducts, and it should compose the antibodies panel aiming at improvement of these differential diagnoses. In contrast, MUC2, MUC5, MUC6 and CD56 were not promising in differentiating all the phases of cholangiocarcinogenesis.

Focal Nodular Hyperplasia is a benign lesion of the liver, which usually presents with one or two localizations. We report the uncommon case of a 51-year-old female who presents with right upper quadrant pain that worsened in the previous month, without association with feeding. Four hepatic lesions were evidenced at Computerized tomography, the largest being of 8 cm in diameter, of atypical behavior. She was submitted to hepatic segmentectomy of the segment III. The pathologic diagnosis returned focal nodular hyperplasia mixed hyperplastic and adenomatous sub-type. The patient had a good postoperative evolution and is in ambulatory follow-up.

O crescimento endobiliar das neoplasias primárias e metastáticas do fígado é raro, com exceção dos colangiocarcinomas. Nas metástases esse comportamento pode suscitar dificuldade no diagnóstico diferencial com colangiocarcinomas quando são analisadas apenas as características morfológicas das neoplasias e/ou quando há associação com anormalidades que sugiram a origem biliar do tumor. Analisamos a imunoexpressão das citoqueratinas (CKs) 7, 19 e 20 em dois casos de metástase hepática de adenocarcinoma colorretal, com disseminação endobiliar, em fígados com adenoma e hamartomas biliares. Em ambos os casos, além da disseminação endobiliar da neoplasia, o epitélio biliar apresentava-se displásico. A neoplasia foi CK 20 positiva, CK 7 negativa, enquanto a CK 19 foi positiva no epitélio biliar normal, no displásico e na neoplasia. A CK 7 foi positiva no epitélio biliar, hamartomas e adenoma. Concluímos que o emprego da CK 7 e da CK 20 é importante em tumores com essa forma de disseminação, sobretudo quando associados aos hamartomas e adenomas biliares.

Endobiliary growth of primary and metastatic liver neoplasias is rare, with exception of cholangiocarcinoma. This behavior, when occurring in metastatic neoplasias, frequently challenges the differential diagnosis of cholangiocarcinomas, mainly when its analysis is based only in morphological characteristics of the neoplasias and/or there is association with abnormalities which suggest biliary origin of the tumor. We analyzed cytokeratins (CKs) 7, 19 and 20 imunoexpression in two cases of colorectal metastatic adenocarcinoma with endobiliary dissemination in livers with biliary adenoma and hamartoma. In both cases, in addition to endobiliary dissemination, there was also dysplasia in the biliary epithelium. The neoplasia was positive for CK 20, negative for CK 7, while the normal epithelium, the dysplatic epithelium and the neoplasia were all positive for CK 19. The CK 7 was positive in the biliary epithelium, in hamartomas and adenoma. We concluded that the use of CK 7 and CK 20 is important in tumors with this type of dissemination, especially when they are associated with harmatomas and biliary adenomas.