Immunohistochemical and Molecular Markers in the Diagnosis of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) has distinct morphologic features and can be identified in the majority of cases by routine hematoxylin and eosin (H&E)-stained formalin-fixed paraffin-embedded sections. However, distinguishing a well-differentiated HCC from normal or regenerative tissue may be very difficult in some cases, particularly in small needle aspiration or core biopsies. Furthermore, some of the unusual morphologic variants, including clear-cell, pleomorphic, and sarcomatoid variants, may be mistaken for metastases. Similarly, metastases from various primary tumors to the liver may be mistaken for primary hepatic tumors. In this overview, we summarize the immunohistochemical and molecular markers that have been developed to address these diagnostic challenges. Among the numerous diagnostic markers studied, pCEA, HepPar 1, CD34, CK 7, CK 19, CK 20, and albumin in situ (ISH) have been found to be valuable in distinguishing HCC from metastatic neoplasms of extrahepatic sites.

Neoplasms of the liver

“…1,16 As the cells of HCC attempt to mimic normal liver cells, they may produce any of the cellular products that can be found in hepatocytes both in health and in disease, and if present, these are readily demonstrated by immunostaining. Many of these can also be found in tumors other than HCC, and so are of little use in differential diagnosis.…”

“…Staining in hepatocellular adenomas is variable, so that a positive stain does not necessarily indicate malignancy. 16,19 Differential Diagnosis A frequent problem in differential diagnosis is in distinguishing poorly differentiated HCC from other malignancies, especially metastases but also from poorly differentiated cholangiocarcinoma (Table 2). A large cell carcinoma with eosinophilic cytoplasm, prominent nuclei and nucleoli may well be HCC but that diagnosis should not be made without definite evidence of hepatocellular differentiation.…”

Intratumoral sampling variability in hepatocellular carcinoma: A case report

“…Furthermore, some of the unusual morphologic variants, including clear-cell, pleomorphic, and sarcomatoid variants, may be mistaken for metastases. Similarly, metastases to the liver from various hepatoid variants of extra-hepatic neoplasms and other primary hepatic tumors, such as cholangiocarcinoma (CC), may be mistaken for HCC [4] . The differential diagnosis of these lesions is often difficult, especially because of the scant material obtained by needle biopsy [5] .…”

“…The differential diagnosis of these lesions is often difficult, especially because of the scant material obtained by needle biopsy [5] . The current literature shows that difficulties in histological typing of liver tumors, particularly in the differential diagnosis between HCC and CC and metastases can be minimized by using immunohistochemistry [4,6] . Among the numerous diagnostic immunohistochemical markers studied, alphafetoprotein (AFP) [7] , CK7 [8] , CK20 [9] , CK19 [10] , hepatocyte paraffin 1 (Hep Par 1) [11,12] and glypican 3 (GPC3) [3,5,13] have been found to be valuable in the diagnosis of HCC.…”

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

“…Immunomarkers thus play an indispensable role when difficult cases are encountered (Table 4). [88][89][90] Hepatocellular Markers CEA and CD10.-Polyclonal anti-CEA antibodies (pCEAs) cross-react with a biliary glycoprotein, giving rise to a characteristic canalicular staining pattern in normal liver. This canalicular pattern is preserved in most HCC cases ( Figure 5), with a sensitivity of 70% to more than 90% in some studies.…”