Types of Hepatocellular Carcinoma
According to the 2025 EASL guidelines, there are nine distinct types of HCC: one "not otherwise specified" (NOS-HCC) category and eight morphological subtypes—fibrolamellar, scirrhous, clear cell, steatohepatitic, macrotrabecular/massive, chromophobe, neutrophil-rich, and lymphocytic-rich. 1
Primary Classification Framework
The WHO classification system recognizes these subtypes based on histopathological features, with significant prognostic implications that should guide post-hepatectomy surveillance and treatment planning 1, 2:
The Eight Morphological Subtypes
Fibrolamellar HCC: Typically occurs in younger patients without underlying cirrhosis and has distinct clinical characteristics 1, 2
Steatohepatitic HCC: Presents with histological features of steatohepatitis including ballooning, steatosis, fibrosis, inflammatory infiltrates, and Mallory-Denk bodies; commonly associated with metabolic dysfunction-associated steatotic liver disease (MASLD) 1, 2
Macrotrabecular/massive HCC: Associated with poor prognosis and aggressive biological behavior, warranting closer post-hepatectomy surveillance 1, 2, 3
Clear cell HCC: Characterized by clear cytoplasm due to glycogen or lipid accumulation 1
Chromophobe HCC: Displays specific morphological features with potential molecular correlates 1
Scirrhous HCC: Contains abundant fibrous stroma 1
Lymphocyte-rich HCC: Associated with better prognosis compared to other subtypes, important for prognostic counseling 1, 2
Neutrophil-rich HCC: Characterized by prominent neutrophilic infiltration 1
Additional Classification Systems Relevant to Post-Hepatectomy Patients
Size-Based Classification for Small Nodules
For hepatocellular nodules <2 cm (critical for surveillance after hepatectomy), two distinct malignant subtypes exist 1:
Early HCC: Vaguely nodular growth pattern with well-differentiated histology; fatty change present in approximately 40% of cases 1
Progressed HCC: Distinctly nodular with moderate to poorly differentiated features; associated with vascular invasion and intrahepatic metastasis 1
Differentiation Grading
Histological grading (well/moderately/poorly differentiated) carries proven prognostic value in surgical and transplantation series and should be reported for all post-hepatectomy specimens 1
Prognostic Implications Critical for Post-Hepatectomy Management
The pathomolecular classification correlates morphological subtypes with biological behavior 1, 2:
Poor prognosis subtypes: Macrotrabecular/massive and progenitor phenotypes require aggressive surveillance protocols 1, 2
Favorable prognosis subtype: Lymphocyte-rich HCC may allow less intensive follow-up 1, 2
Intermediate subtypes: NOS-HCC and other variants follow standard surveillance protocols 1
Clinical Recommendation for Post-Hepatectomy Patients
If a biopsy was obtained or surgical specimen is available, the pathology report must include tumor differentiation and HCC subtyping per WHO classification, as this directly impacts recurrence risk stratification and surveillance intensity 1. The macrotrabecular/massive subtype in particular should trigger enhanced surveillance given its association with high recurrence rates 2, 3.
Key Diagnostic Pitfall
When reviewing pathology reports, ensure the specific subtype is documented—not just "HCC"—as the 2025 EASL guidelines strongly recommend subtyping for prognostic assessment 1. If subtyping was not performed on the original hepatectomy specimen, consider requesting re-review by an expert hepatopathologist 1.