Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.

Keywords: Biomarker; Biopsy; Diagnosis; Hepatocellular carcinoma; Histopathology; Immunohistochemistry; Molecular; Prognosis; Targeted therapy.

Figure 1

Hepatocellular carcinoma Edmondson and Steiner grading. Grade 1 (A); grade 2 (B); grade 3 (C); and grade 4 (D). Most common patterns in histopathology of hepatocellular carcinoma: Microtrabecular (E); pseudoglandular (F); macrotrabecular (G); and compact (H). (HE stain).

Figure 2

Gross morphology of hepatocellular carcinoma. Single expanding nodular hepatocellular carcinoma (A); vaguely nodular with perinodular extension (B); Multinodular (C); multicentric with cirrhotomimetic appearance (D); nodular with satellite nodules (E); pedunculated (F); infiltrative (G); and hepatocellular carcinoma in non-cirrhotic background (H).

Figure 3

Hepatocellular carcinoma variants, subtypes and histological features. Macrotrabecular (A); steatohepatitic (B); sarcomatoid (C); cholangiocellular (D); sclerosing (E); combined HCC-CC (F); HCC with foam cells (G); HCC with giant cells and hyaline bodies (H); clear cell (I); fibrolamellar (J); HCC with immune cells (K); CK19 positive stem cells (L). HCC: Hepatocellular carcinoma.

Figure 4

Dysplastic lesions and early hepatocellular carcinoma. Gross morphology of small distinctly nodular HCC (A); small vaguely nodular HCC (B, C); HCC with nodule in nodule appearance (D). Microphotographs of large cell change (E) and small cell change (F) in dysplastic nodules. Nodule in nodule with low grade dysplasia surrounding central high grade dysplastic nodule (G) on HE stain and focal CD34 positive (H) on immunohistochemistry. Glypican-3 (I), glutamine synthetase (J), HSP-70 (K) and diffuse CD34 (L) immunostaining in well-differentiated HCC. HCC: Hepatocellular carcinoma.