Progress in pathologyImmunohistochemical approach for the diagnosis of a liver mass on small biopsy specimens☆
Introduction
The distinction of hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma or metastatic tumor can be challenging on cell block or core biopsy specimens. This review summarizes the challenges in the use of immunohistochemistry for the diagnosis of HCC and suggests specific panels depending on the clinical setting. The review is divided into five parts:
(A) Advantages and pitfalls of commonly used antibodies.
(B) Selection of antibody panel for diagnosis of HCC.
(C) HCC versus other polygonal cell tumors.
(D) Immunohistochemistry in histologic variants of HCC and other related settings.
(E) HCC versus benign hepatocellular lesions.
Section snippets
Hepatocyte paraffin-1
Hepatocyte paraffin-1 (Hep Par-1) is a monoclonal antibody developed using formalin-fixed tissue from failed liver allografts [1]. It recognizes a hepatocyte-specific antigen, which is now known to be carbamoyl phosphate synthetase I, a urea cycle enzyme [2]. Hep Par-1 is a useful marker for diagnosis of HCC with sensitivity and specificity exceeding 80% [3], [4], [5], [6], [7], [8]. It shows a diffuse cytoplasmic granular staining pattern, which is easy to interpret. Most adenocarcinomas
Selection of antibody panel for diagnosis of HCC
If hepatocellular differentiation is obvious based on histologic features (e.g., bile production), immunohistochemistry is not necessary for diagnosis, especially in the setting of cirrhosis. In most other situations especially in non-cirrhotic liver, a panel of 4 antibodies is recommended, including two hepatocellular markers (preferably Arg-1 and GPC-3) and two markers that are more commonly seen in adenocarcinoma (such as CK19 and MOC-31). If limited tissue is available, a two-stain approach
HCC versus other polygonal cell tumors
The term polygonal cell tumors refers to tumors that morphologically resemble HCC and includes epithelial neoplasms like RCC and NET as well as non-epithelial tumors like melanoma, ACC, AML, and sarcomas with epithelioid morphology.
Scirrhous HCC
Scirrhous HCC is a rare variant of HCC characterized by a prominent stromal component, which comprises more than 50% of the tumor (Fig. 2A) [9], [64], [65], [66]. Hep Par-1 and pCEA have low sensitivities in scirrhous HCC (26% and 37%, respectively) [9]. Scirrhous HCC is positive for CK7, CK19, and MOC-31 in more than half of the cases (Fig. 2B). The abundant stroma and aberrant immunophenotype can lead to an erroneous diagnosis of metastatic adenocarcinoma or intrahepatic cholangiocarcinoma [9]
Hepatocellular adenoma
The absence of cytologic atypia (small cell change, nuclear pleomorphism), lack of architectural abnormalities (thick cell plates, prominent pseudoacinar change), and an intact reticulin framework distinguish HCA from HCC [75], [78], [79]. Immunohistochemistry can be helpful in distinguishing HCA from HCC in small samples, and also helps in the classification of HCA into four categories based on the WHO 2010 classification.
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Disclosures: None Declared.