An update on the histological subtypes of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the top-ranking cancers worldwide and in Southeast Asia. The high propensity for tumor recurrence, distant metastasis and chemoresistance remain major hurdles in the treatment of HCC. With advances on genetics and genomics research, molecular targeted therapies are emerging as a hope for better disease control. On the histological perspective, microscopic review of clinical samples has led to subclassification of HCC and establishment of new entities. In this review, latest understanding on macrotrabecular-massive HCC, steatohepatitic HCC, lymphocyte-rich HCC, scirrhous HCC, fibrolamellar carcinoma and combined hepatocellular-cholangiocarcinoma will be discussed, emphasizing on the clinical relevance of these pathological entities. Further delineation of the histological, immunohistochemical, molecular and biological phenotypes of primary liver cancer would to further enhance an integrated morphological-molecular classification that better predicts clinical outcome and guides clinical management.

Lymphocyte-Rich Hepatocellular Carcinoma with Multiple Lymphadenopathy and Positive Epstein–Barr Virus Encoding Region

“…Immunohistochemistry analysis of lymphocyte-rich HCC demonstrates positive expression for cytokeratin and markers of hepatic differentiation, such as arginase, glypican 3, and hepatocyte paraffin 1 [ 12 ]. Tumor-infiltrating lymphocytes in lymphocyte-rich HCC mainly consist of CD3 and CD8 positive T lymphocytes, along with scattered CD20 positive B-lymphocytes [ 3 , 13 ].…”

A Case of Lymphocyte-Rich Hepatocellular Carcinoma in a Patient Who Was Treated for Colon Cancer

“…11 It has also been referred to as lymphoepithelioma-like HCC. 5,9,10 Histologic findings of this subtype are characterized by massive intratumoral infiltration of lymphocytes. 4,5,9 In 1998, Wada et al 12 reported that it was defined by the presence of more than 100 tumor-infiltrating lymphocytes in 10 high-power fields.…”

“…5,9,10 Histologic findings of this subtype are characterized by massive intratumoral infiltration of lymphocytes. 4,5,9 In 1998, Wada et al 12 reported that it was defined by the presence of more than 100 tumor-infiltrating lymphocytes in 10 high-power fields. Although lymphocyte infiltration needs to be observed for its di-agnosis, a unified definition for the density of lymphocytes required for diagnosis has not been established.…”

“…However, HCCs are heterogonous in pathogenesis, and further studies have been performed to classify the subtypes of HCC, specifically based on the morphological characteristics of tumor cells. 4 , 5 Primary hepatic tumors that have distinct pathologic features are known as HCC variants. 6 As many as 35% of HCCs can now be classified into histopathological variants.…”