Imaging Correlates of Molecular and Pathological Subtypes in Hepatocellular Carcinoma

Overview

Hepatocellular carcinoma (HCC) exhibits significant molecular and pathological heterogeneity that impacts prognosis and treatment response. Noninvasive imaging techniques such as multiphase CT and multiparametric MRI show promise in predicting molecular and pathological subtypes, potentially guiding individualized management without the need for invasive tissue sampling.

Background

HCC is a biologically heterogeneous malignancy with diverse molecular and pathological subtypes influencing recurrence, metastasis, and therapeutic outcomes. Molecular classification broadly divides HCC into proliferative and non-proliferative classes, each with distinct genetic and clinical features. Pathological classification identifies conventional and eight distinct histological subtypes, some correlating with molecular classes. Current clinical practice relies on invasive biopsy for subtype classification, which is limited by sampling errors and availability.

Data Highlights

The proliferative class accounts for approximately 50% of HCC cases and is associated with chronic HBV infection, higher serum AFP and DCP levels, and aggressive tumor behavior. The non-proliferative class predominates in ALD, MASH, and HCV-related HCCs and is linked to less aggressive phenotypes and lower AFP levels. Molecular pathways enriched in proliferative HCC include PI3K-AKT-mTOR and RAS-MAPK, while non-proliferative tumors show CTNNB1 and TERT promoter mutations. Pathologically, 65% of HCCs are conventional, with the remainder distributed among eight subtypes such as macrotrabecular-massive and steatohepatitic, which correlate variably with molecular classes.

Key Findings

• HCC molecular classification divides tumors into proliferative and non-proliferative classes with distinct genetic and clinical profiles.
• Proliferative HCCs are linked to chronic HBV infection, aggressive behavior, and elevated serum tumor markers (AFP, DCP).
• Non-proliferative HCCs are more common in ALD, MASH, and HCV-related cases, showing less aggressive features and lower AFP levels.
• Pathological subtypes include conventional HCC and eight distinct variants, some of which correspond to molecular classes (e.g., macrotrabecular-massive with proliferative class).
• Multiphasic CT and multiparametric MRI can capture imaging features that correlate with molecular and pathological subtypes, offering a noninvasive classification approach.
• Imaging-based subtype prediction may improve prognostication and guide personalized therapy, especially when biopsy is unavailable or limited.

Clinical Implications

Noninvasive imaging modalities hold potential to infer HCC molecular and pathological subtypes, facilitating risk stratification and therapeutic decision-making without invasive biopsy. Recognizing imaging biomarkers associated with aggressive proliferative tumors may prompt closer surveillance and tailored treatment strategies. Integration of imaging with clinical and laboratory data could enhance individualized patient management in HCC.

Conclusion

Understanding the correlations between imaging features and HCC molecular and pathological subtypes may enable noninvasive tumor classification, improving prognostication and personalized treatment. Further research is needed to validate imaging biomarkers and integrate them into clinical workflows.

References

1. Comprehensive Review 2024 -- Evaluating Imaging Techniques for Molecular and Pathological Classification of Hepatocellular Carcinoma