Clinicopathological Study on Morphological Subtypes of Hepatocellular Carcinoma: A Single Tertiary Referral Center Experience

Abstract

Aim: We aimed to analyze hepatocellular carcinoma (HCC) morphological subtypes characterized according to the WHO classification and the International Collaboration on Cancer Reporting (ICCR) recommendations, and their prognostic features in a Dutch population.

Methods and results: This retrospective study in a tertiary referral center included the histopathological revision of 62 HCC resection specimens, obtained from 22 female and 40 male patients (median age: 67 years), in a period between 2011 and 2021 at the Maastricht University Medical Center +. Clinical data, morphological subtypes, growth pattern (GP), tumor grade, tumor extension, margins, and vascular and perineural invasion were collected. Eighteen cases were assigned a specific morphologic subtype and steatohepatic HCC was the most common in our cohort. Twenty-one tumors classified as conventional type HCC (HCC-NOS), commonly exhibiting two concurrent GPs. Twenty-three cases revealed a heterogeneous morphologic differentiation, compromising the combination of HCC-NOS with another morphologic subtype, most frequently a steatohepatitic component. Comparison of HCC-NOS and HCC with heterogeneous morphology did not show significant differences in the main clinicopathological characteristics and survival.

Conclusion: Although the most common morphologic subtype was steatohepatitic HCC, the majority of cases demonstrated multiple morphologic patterns. In case of HCC-NOS, heterogeneous GPs were often observed. Therefore, a histomorphological diagnosis based on a single tumor biopsy specimen may lead to incorrect classification of HCC. Sufficient tumor sampling of HCC resection specimens is required for the complete evaluation of all histomorphological features followed by correct subclassification in order to meet the clinical needs regarding prognostic relevance and patient follow-up.

Keywords: cancer care; liver cancer; pathology; tumor heterogeneity.

FIGURE 1

Schematic description of the classification of the cases according to morphologic subtype and growth pattern suggested by the WHO 2019 classification.

FIGURE 2

Hepatocellular carcinoma, conventional type (HCC‐NOS) with different growth patterns (hematoxylin–eosin stain, 20× magnification). (A) Trabecular growth pattern. The arrows highlight the thickened trabeculae of polygonal, eosinophilic tumor cells; (B) Pseudoglandular growth pattern. The arrows show dilated acinar structures, lined with a layer of neoplastic cells, often with fluid in the lumen; (C) Macrotrabecular growth pattern. The arrows highlight the large thickened trabeculae, being ≥ 10 cells thick. (D) Solid growth pattern. The arrows show compact growth of the neoplastic cells.

FIGURE 3

Steatotic hepatocellular carcinoma (hematoxylin–eosin stain, 20× magnification). In all three demonstrated cases (A–C), neoplastic cells showed macrovesicular steatosis and a different degree of ballooning, highlighted by arrows.

FIGURE 4

Clear cell hepatocellular carcinoma (hematoxylin–eosin stain, 20× magnification). Neoplastic cells showed clear cytoplasm in all three demonstrated cases (A–C), indicated with arrows.

FIGURE 5

Rare subtypes of hepatocellular carcinoma (hematoxylin–eosin stain, 20× magnification). (A) Chromophobe HCC. The arrows show neoplastic cells with smooth clear cytoplasm with distinct cell membranes; (B) HCC with osteoclast‐like giant cells. The arrows indicate the large multinucleated cells with eosinophilic cytoplasm. (C) HCC with syncytial giant cells. The arrows show intratumoral giant cells with atypical nuclei.