Elsevier

Human Pathology

Volume 63, May 2017, Pages 1-13
Human Pathology

Progress in pathology
Immunohistochemical approach for the diagnosis of a liver mass on small biopsy specimens☆

https://doi.org/10.1016/j.humpath.2016.12.025Get rights and content

Highlights

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    HCC shares overlapping histological features with benign hepatocellular lesions.

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    Metastatic tumors can be indistinguishable from HCC on histologic grounds.

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    IHC markers play an important role in establishing an accurate diagnosis.

Summary

Well-differentiated hepatocellular carcinoma (HCC) shares overlapping histological features with benign hepatocellular lesions, including hepatocellular adenoma and focal nodular hyperplasia in non-cirrhotic liver, and with high-grade dysplastic nodule in cirrhotic liver. Several metastatic tumors, such as neuroendocrine tumor, renal cell carcinoma, adrenocortical carcinoma, melanoma, and epithelioid angiomyolipoma, can be indistinguishable from HCC on histologic grounds. Since this distinction has important therapeutic implications, judicious use of immunohistochemical markers plays an important role in establishing an accurate diagnosis, especially when limited material of tumor is available on cell block or a small core biopsy. This review describes commonly used immunohistochemical markers used in the diagnosis of HCC, highlighting advantages and disadvantages of each marker, and suggests appropriate immunohistochemical panels for specific clinicopathologic situations.

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.

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