Which markers comprise the IHC panel for primary hepatocellular carcinoma?

• A. AFP, HepPar1, CAM5.2, CD34, GPC3
• B. AFP, CK7, CK20
• C. CA19-9, CK7, CK20
• D. Napsin A, HepPar1

Answer: (A)

Immunohistochemical profiling for hepatocellular carcinoma relies on recognizing hepatocytic differentiation and the distinctive vascular pattern these tumors often show. HepPar1 is a classic marker of hepatocyte lineage, so its positivity points toward hepatocytic origin. Glypican-3 (GPC3) is more specific for HCC and helps distinguish it from benign liver lesions and many other tumors. Alpha-fetoprotein (AFP) staining supports hepatocellular differentiation when present, even though not all HCCs express it; its presence adds diagnostic weight. CAM5.2 detects low molecular weight cytokeratins (CK8/18), reflecting epithelial characteristics of hepatocytes and aiding separation from non-hepatocytic biliary tumors. CD34 highlights the sinusoidal capillarization pattern seen in HCC, a vascular feature that contrasts with the vascular patterns of metastases or cholangiocarcinoma. Taken together, this combination of markers builds a coherent immunoprofile for primary hepatocellular carcinoma, increasing diagnostic confidence more than any single marker alone. The other marker sets focus more on cholangiocarcinoma, pancreaticobiliary, or lung origins and are less supportive of a hepatocellular diagnosis.