Diffuse MOC-31 Expression in Hepatocellular Carcinoma: A Diagnostic Challenge

Introduction: Distinguishing hepatocellular carcinoma (HCC) from other primary liver tumors and metastatic carcinomas involving the liver can be problematic, especially in cases which do not exhibit classic hepatocellular morphology or immunohistochemistry (IHC). The clinical history including chronic viral infections, metabolic syndrome, alcohol, cirrhosis, and alpha-fetoprotein levels (AFP) can often help in this distinction. However, hepatoid adenocarcinoma (HAC), a rare but distinct entity, enters the list of differentials as it closely mimics HCC and may not be distinguished based on histology or immunohistochemistry. HAC is known to be aggressive and has limited therapeutic options; hence its distinction from HCC is crucial.

Case presentation: A 54 year old female with a remote history of ovarian cancer presented with multiple liver masses (largest 8 cm) with Hepatitis C infection (RNA quantitative 3700000 IU/ml), and alpha-fetoprotein >2000ng/ml. The chest, abdomen, and pelvis imaging were negative for cirrhosis, masses or lymphadenopathy at other sites. Histologically, the biopsy from liver mass showed tumor cells arranged in macrotrabecular pattern and nests with focal pseudopapillary architecture with macrophages. An immunohistochemical panel showed diffuse strong positivity for glypican, MOC-31 (membranous), Hep-par 1, pancytokeratin and patchy positivity for arginase in tumor cells. CK7, CK20, ER, PR, PAX-8, TTF-1, and p63 were negative. Albumin in-situ hybridization (ISH) was diffusely positive in tumor cells.

Discussion: The morphology and immunohistochemical staining with glypican, Hep-par 1, arginase and albumin ISH favored hepatocellular carcinoma, but the strong expression of MOC-31 which is used to differentiate HCC from cholangiocarcinomas, and metastatic adenocarcinomas added to the diagnostic confusion. MOC-31 is found to be positive in only a subset of HCC cases reported in the literature. The absence of CK7, CK20, ER, PR, TTF-1, p63 and PAX-8 essentially excluded primaries from elsewhere. Nevertheless, the possibility of metastasis from hepatoid adenocarcinoma of other sites was stated and a clinical correlation was recommended.

Keywords: MOC-31; Hepatocellular carcinoma; Hepatoid adenocarcinoma

Abbreviations: HCC: Hepatocellular Carcinoma; ICC: Immunohistochemistry; HAC: Hepatoid Adenocarcinoma; ISH: In-Situ Hybridization; AFP: Alpha-Fetoprotein