Current concepts in the immunohistochemical evaluation of liver tumors

Abstract

Immunohistochemistry often plays an important role in the evaluation of liver tumors. Recent advances have established a classification system for hepatocellular adenomas (HCAs) based on morphology, molecular alterations, and immunohistochemistry. Specifically, loss of liver fatty acid binding protein is seen in HNF1α-inactivated HCA, staining with serum amyloid A is seen in inflammatory HCA, and diffuse staining with glutamine synthetase (GS) is seen in β-catenin activated HCA. A panel of immunohistochemical stains including glypican-3 (GPC-3), heat shock protein 70, and GS are useful in distinguishing HCC from non-malignant dysplastic nodules. Immunohistochemistry is also useful to determine whether a liver tumor is of primary hepatocellular or metastatic origin. Recently described markers useful for this purpose include arginase-1, GPC-3, and bile salt export pump. These newer markers may offer superior utility when compared to traditional markers of hepatocellular differentiation such as alpha-fetoprotein, hepatocyte paraffin-1, polyclonal carcinoembryonic antigen, and CD10. This paper will review recent advances in the immunohistochemical evaluation of liver tumors.

New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges

“…However, at present, there is still lack of sensitive and special molecular markers available for the differential diagnosis between dysplastic nodules and early HCC, although there are increasing biomarker panels waiting for multi-centric validations (Table 1). Comparatively, there are a few proposed immunohistochemical markers, such as glypican-3 (GPC-3), heat-shock protein-70 (HSP-70), glutamine synthetase (GS), CD34 and sulfite oxidase (SUOX), which might help to distinguish above two entities [49,50].…”

Update on hepatocellular carcinoma: Pathologists’ review

“…Therefore, a well differentiated HCC recapitulates benign liver tissue, mimicking the following benign and pre-neoplastic entities: hepatocellular adenoma, focal nodular hyperplasia (FNH), regenerative nodule, and dysplastic nodule in cirrhotic liver. In order to demonstrate malignancy in a well-differentiated HCC that morphologically resembles benign hepatocytic lesions, IHC such as CD34 (showing diffuse sinusoidal capillarization), and a panel of glutamine synthetase (GS), glypican-3 (GPC-3) and heat shock protein 70 (HSP-70) may be helpful[4,5]. Reticulin special stain remains a very useful test, as the aforementioned benign and pre-neoplastic entities generally retain a reticulin network, whereas HCC does not.…”

“…While it would be relatively straightforward to document malignancy based on histomorphology, documenting that the tumor demonstrates immuno-histochemical evidence of hepatocellular phenotype, and excluding other lines of differentiation are necessary in arriving at the correct diagnosis of HCC. Several immuno-histochemical markers including hepatocyte in paraffin 1 (HepPar1), Arginase-1, CD10, polyclonal carcinoembryonic antigen, bile salt export pump and GPC-3 have been utilized in this setting with variable sensitivities and specificities depending on the degree of differentiation of HCC[3,4,7,8]. One study suggested that a combination of Arginase 1 and GPC-3 has the highest sensitivity in determining a hepatocellular origin of a poorly differentiated carcinoma[9].…”

Saudi Association for the Study of Liver diseases and Transplantation practice guidelines on the diagnosis and management of hepatocellular carcinoma

“…To determine malignancy in a well-differentiated HCC that morphologically resembles benign hepatocytic lesions, immunohistochemical staining for CD34 (showing diffuse sinusoidal capillarization), and a panel of glutamine synthetase (GS), glypican-3 (GPC-3), and heat shock protein 70 (HSP-70) can be used. [ 102 103 ] Both, the International Consensus Group of Hepatocellular Neoplasia and the WHO have adopted this three-marker panel in their recommendations. [ 104 ] In addition to this, reticulin special stains can be useful, as the aforementioned benign and pre-neoplastic entities generally retain a reticulin network, while this is not the case for HCC.…”