The strengths and weaknesses of gross and histopathological evaluation in hepatocellular carcinoma: a brief review

Abstract

Careful pathological analysis of hepatocellular carcinoma (HCC) specimens is essential for definitive diagnosis and patient prognostication. Tumor size and focality, gross patterns, macro-and microvascular invasion, degree of histological differentiation and expression of Keratin 19 (K19) are relevant features for risk stratification in this cancer and have been validated by multiple independent cohorts. However, there are important limitations to pathological analyses in HCC. First, liver biopsies are not recommended for diagnosis according to current clinical guidelines. Second, there is limited morphological data from patients at intermediate, advanced and terminal disease stages. Finally, there is little consensus on the evaluation of key histopathological features, notably histological grading (degree of differentiation). Here, we review important morphological aspects of HCC, provide insights to molecular events in relation to phenotypic findings and explore the current limitations to pathological analyses in this cancer.

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

“…1 Many clinical factors are important in the prognosis of patients with HCC, including disease stage, Eastern Cooperative Oncology Group performance status (ECOG PS), histopathology, liver function and serum alphafetoprotein (AFP) levels. [2][3][4] Elevated AFP in patients with HCC is associated with worse prognosis compared with the general HCC population. [5][6][7][8][9] It has been shown that incremental changes in AFP levels (10-<100, 100-<1000 and ≥1000) at the time of HCC diagnosis are significantly associated with increased mortality independent of several demographic factors, clinical factors or treatment.…”

Macroscopic Characterization of Hepatocellular Carcinoma: An Underexploited Source of Prognostic Factors

“…34–36 Likewise, the KLCA simplified HCC classification into five categories: (I) vaguely nodular, (II) expanding nodular, (III) multinodular confluent, (IV) nodular with peri-nodular extension and (V) infiltrative. 8 , 36 …”

“…Although trivial, it is coherent to leverage the genotype-to-phenotype sequence to support that the macroscopic appearance of HCC is unlikely random but rather reflects genomic traits of these tumors and may thus be highly contributive. 8 Gross examination may be an underestimated and underexploited source of prognostic markers in HCC.…”

Radiologic-Pathologic Correlation of Liver Tumors

“…Hepatocellular carcinoma (HCC) (Figure 3) is a malignant hepatocellular neoplasm, commonly occurring in the setting of underlying chronic liver disease (2). Traditionally, macroscopic patterns of HCC are described as single or multiple liver nodules, massive nodules that may involve multiple liver segments, and diffuse forms with multiple small nodules throughout the liver mimicking cirrhosis (16). Tumor nodules smaller than the main tumor and less than 2 cm away (separated by non-neoplastic parenchyma) are classified as satellite nodules and usually represent intrahepatic metastases.…”

“…Tumor nodules smaller than the main tumor and less than 2 cm away (separated by non-neoplastic parenchyma) are classified as satellite nodules and usually represent intrahepatic metastases. Nodules that are far from the primary tumor may represent either synchronous tumors or intrahepatic metastases (16). Involvement and spread through intrahepatic portal vein branches are common.…”