Hepatocellular Carcinoma: Clinicopathologic Associations Amidst Marked Phenotypic Heterogeneity

Background: Hepatocellular carcinoma (HCC) is characterized by marked phenotypic and molecular heterogeneity. Clinico-morphologic phenotypes and associations are important surrogate markers of molecular aberrations; therefore have immense relevance for targeted therapy. There is paucity of published literature on critical analysis of HCC heterogeneity and morphological alliance. Aims: To assess the heterogeneity and dominance of histomorphological features, and to explore clinicopathological associations in HCC. Methods: Retrospective cross-sectional study of 217 HCC tissue specimens was performed for the assessment of prevalence of major histological patterns, cytological features, and clinicopathological correlation. Results: Homogeneous architecture with a single dominant histological pattern was a rarity. Single pattern constituting >= 50 % of the tumour was found in less than 1/5th of the cases. Macrotrabecular HCC represented 9.2 % of cases. The simultaneous presence of 2-3 patterns or atypical variants and/ or cytological characteristics was recorded in 25 % and 30 % respectively. Significant clinicopathological associations: Pseudoglandular with microtrabecular pattern-cholestasis, showed better differentiation and early-stage; macrotrabecular pattern frequently occurred with pleomorphic giant cells, higher tumour stage, higher AFP levels; solid pattern often showed clear cells. Noticeable mutual exclusions were MD bodies with microtrabecular and pseudoglandular patterns; Compact pattern with neutrophilic clusters and cholestasis. Larger tumours were significantly more heterogeneous; however, heterogeneity did not correlate with outcome Conclusions: HCC displays immense heterogeneity with an amalgamation of different histomorphological patterns and features; nevertheless, there are certain reproducible associations and omissions. Tumor biopsies agree fairly well with large specimens. Characterization of phenotypic heterogeneity, dominance, associations, and exclusions in individual patients provides vital information.