Combined hepatocellular-cholangiocarcinoma and its mimickers: Diagnostic pitfalls in surgical pathology

• Published in: Annals of diagnostic pathology 2021-08, Vol.53, p.151770-151770, Article 151770
• Main Authors: Laohawetwanit, Thiyaphat, Lerttanatum, Nathawadee, Wanpiyarat, Natcha, Manasilp, Natcha, Chaiparnich, Sirawich
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Mucinous - pathology; Adult; Aged; Biopsy - methods; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - therapy; Chemoembolization, Therapeutic - methods; Cholangiocarcinoma - diagnosis; Cholangiocarcinoma - pathology; Cholangiocarcinoma - surgery; Cholangiocarcinoma - therapy; Combined hepatocellular-cholangiocarcinoma; Female; Histopathology; Humans; Immunohistochemistry; Immunohistochemistry - methods; Intrahepatic cholangiocarcinoma; Liver - metabolism; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - pathology; Liver Neoplasms - epidemiology; Liver Neoplasms - pathology; Liver Neoplasms - ultrastructure; Male; Margins of Excision; Middle Aged; Neoplasms, Multiple Primary - epidemiology; Neoplasms, Multiple Primary - pathology; Neoplasms, Multiple Primary - ultrastructure; Pathology, Surgical - statistics & numerical data; Prevalence; Prognosis; Retrospective Studies; Tertiary Care Centers; Thailand - epidemiology
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2021.151770

The diagnosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) requires histomorphological detection of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). However, these primary liver cancers (PLCs) have a wide variety of microscopic appearances resulting in difficulties and uncertainties in cHCC-CCA's diagnosis. This study aims to perform a clinicopathologic analysis on the diagnosis of PLCs at a tertiary referral hospital in Thailand using traditional morphologic studies. A 5-year retrospective analysis of pathologically diagnosed PLCs was conducted. Pathological features and clinical characteristics of cHCC-CCA and other PLCs with the histopathologic resemblance to cHCC-CCA were studied. The pathological diagnosis was rendered based on histomorphological context rather than immunoreactivity. A literature review containing diagnostic pitfalls of cHCC-CCA was carried out. PLCs from a total of 295 patients were retrieved, and cHCC-CCA accounted for 1.4% (n = 4) of the malignancies. Histomorphological evaluation is the most reliable diagnostic modality for cHCC-CCA. Extremely uncommon variants of iCCA (i.e., mucinous iCCA and adenosquamous iCCA) and iCCA arising with hepatocellular nodular lesions (i.e., iCCA with nodular regenerative hyperplasia (NRH), and iCCA in cirrhosis) could have a histomorphologic resemblance to that of cHCC-CCA. Although there has been an exceedingly high incidence of iCCA in Thailand, such a commonness is not valid for cHCC-CCA in our series. Rare forms of iCCA could have a morphologic resemblance to that of cHCC-CCA. Regardless of the differentiation and immunophenotype, iCCA without a distinct HCC component should never be diagnosed as cHCC-CCA. •Routine histomorphological evaluation is the most reliable diagnostic modality for combine hepatocellular-cholangiocarcinoma (cHCC-CCA).•Overutilization of immunohistochemical markers results in overdiagnosis of cHCC-CCA.•Extremely rare variants of intrahepatic cholangiocarcinoma (iCCA) and iCCA intermixed with hepatocellular nodular lesions (i.e., nodular regenerative hyperplasia and cirrhosis) could have a histomorphologic resemblance to that of cHCC-CCA.