Cytokeratin 20 Positive with HepPar-1 Negative in Hepatocellular Carcinoma - A Potential Diagnostic Pitfall in the Pathological Interpretation of Needle Core Liver Biopsy

Abstract

Needle core biopsy of liver lesions in adults with a clinical query of metastases is commonly encountered in general surgical pathology practice. The presence of poorly differentiated malignant cells forming ill-formed glands favors a working pathological diagnosis of metastatic carcinoma. If metastatic, determination of the primary site of origin is the next diagnostic challenge that faces the pathologist. An algorithmic IHC approach using cytokeratins and lineage markers often narrows the diagnostic possibilities with definition of tumor type and assigns site of origin. However, aberrant staining patterns are major potential diagnostic pitfalls. We present the case of a needle core liver biopsy with a poorly differentiated pseudoglandular HCC component that showed diffuse Cytokeratin (CK) 20 positivity with absent CK7 and Hepatocyte Paraffin-1 (HepPar-1) staining that was initially misinterpreted as metastatic adenocarcinoma from the lower gastrointestinal tract. However, with systematic integration of complete clinical, endoscopic and radiological data with reevaluation of the surrounding ‘non-neoplastic’ liver, the pathological diagnosis confirmed the presence of hepatocellular carcinoma arising in a background of chronic hepatitis C related cirrhosis, with a poorly differentiated pseudo glandular component associated with loss of HepPar-1 staining and aberrant strong diffuse positivity with CK20 posing as a diagnostic pitfall in the interpretation of limited material on needle core biopsies of mass lesions in an adult liver. We conclude with key learning points in the diagnostic interpretation of needle core liver biopsies from mass lesions in an adult liver with an underlying caveat to “never diagnose liver biopsies in ‘pathological isolation”