Precision pathology analysis of the development and progression of hepatocellular carcinoma: Implication for precision diagnosis of hepatocellular carcinoma

Abstract

Outcomes for patients with hepatocellular carcinoma (HCC) remain poor because the condition is often unresponsive to the available treatments. Consequently, the early and precise diagnosis of HCC is crucial to achieve improvements in prognosis. For patients with chronic liver disease, the assessment of liver fibrosis is also important to ascertain both the staging of fibrosis and the risk of HCC occurrence. Early HCC was first described in 1991 in Japan and was defined internationally in 2009. As the concept of early HCC spread, the multistage hepatocarcinogenesis process became accepted. Consequently, improvements in imaging technology made the early diagnosis of HCC possible. At present, the most appropriate therapeutic strategy for HCC is determined using an integrated staging system that assesses the tumor burden, the degree of liver dysfunction and the patient performance status; however, pathological and molecular features are not taken into account. The recent introduction of several new therapeutic agents will change the treatment strategy for HCC. Against this background, HCC subclassification based on tumor cellular and microenvironmental characteristics will become increasingly important. In this review, we give an overview of how pathological analysis contributes to understanding the development and progression of HCC and establishing a precision diagnosis of HCC.

Gd-EOB-DTPA-MRI Could Predict WNT/β-Catenin Mutation and Resistance to Immune Checkpoint Inhibitor Therapy in Hepatocellular Carcinoma

“…In a recent research breakthrough, the HBP of EOB-MRI predicted the WNT/β-catenin mutation that induces OATP1B3 [15,33]. This suggests that EOB-MRI can be useful in the clinical setting for identifying the immune exclusion class that is highly unlikely to respond to ICI monotherapy.…”

“…These predictions were successfully proven clinically in the study of Harding et al [13] mentioned earlier. In contrast, high PD-L1 expression is associated with CK19 and SALL4 expression, and ICI monotherapy should be effective in HCC with these characteristics [8,33,34] (Fig. 2, 5).…”

Limited Impact of Anti-PD-1/PD-L1 Monotherapy for Hepatocellular Carcinoma

“…One possible reason for the low PD rate of combination therapy with TKI is that lenvatinib and other multikinase inhibitors cause greater tumor necrosis and release of tumor antigens than bevacizumab, and therefore combination therapy with TKI enhances immune response against Teng's type II HCC. Combination regimens with an ICI plus an anti-VEGF antibody or TKI should be effective against tumors with WNT/β-catenin mutations [23][24][25][26] (Fig. 3).…”

Immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications

“…These tumors are further subclassified according to histopathological tumor grade (e.g., well, moderately, poorly differentiated), appearance of tumor cell and tumor stroma, driver gene mutations and molecular signatures, some of which are significantly associated with clinicopathological findings, while others are not. [2][3][4] In HCC, current WHO classification highlights several histopathological subtypes with characteristic stromal features. 1 Lymphocyte-rich HCC, formerly known as lymphoepithelioma-like HCC, is characterized by marked infiltration of lymphocytes into tumor nests and associated with a significantly better prognosis.…”

“…2,3,7,8 At the same time, novel findings from molecular analysis have been applied to the routine pathological assessment of liver carcinoma. [1][2][3][4]7,8 Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains fibroblasts, endothelial cells, pericytes, extracellular matrix and immune cells, forming a complex tumor microenvironment.…”