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Immunohistochemical marking in the diagnosis of combined hepatocellular and cholangiocellular carcinoma: a systematic review

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Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and biologically aggressive primary hepatic neoplasm, accounting for approximately 2% to 5% of liver tumors. This malignant neoplasm is defined by the coexistence of hepatocellular and cholangiocytic differentiation within the same tumor, integrating morphological and molecular features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Its phenotypic heterogeneity contributes to complex clinical behavior and is associated with a poor prognosis, often worse than isolated HCC or CC. Diagnosing cHCC-CCA remains challenging due to overlapping imaging findings and conflicting biomolecular profiles. Currently, the gold standard for definitive diagnosis is histopathological analysis, with immunohistochemistry (IHC) serving as an essential complementary tool to identify the tumor components. Markers such as arginase-1 (Arg-1), HepPar-1, cytokeratin 18 (K18), cytokeratin 7 (K7), and cytokeratin 19 (K19) are commonly employed to aid in tumor characterization. However, variability in marker expression hampers diagnostic standardization. This study aims to systematize existing evidence on the use of Arg-1, HepPar-1, K18, K7, and K19 in the diagnosis of cHCC-CCA, evaluating their impact on the standardization of diagnostic criteria for this carcinoma.

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Hepatic neoplasm Combined hepatocellular-cholangiocarcinoma Immunohistochemical marking Systematic review

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Quintas C, Alves M, Silva V, Mendonça P, Borges-Ferro A. Immunohistochemical marking in the diagnosis of combined hepatocellular and cholangiocellular carcinoma: a systematic review. In: III Congresso Nacional da BioMedLab, Auditório Prof. Armando Simões dos Santos, Faculdade de Medicina Dentária, Universidade de Lisboa, 7 a 9 de março de 2025.

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