Table 2 HCC histological subtypes

Steatohepatitic HCC

Presence of steatohepatitic features such as cell ballooning and steatosis in more than 50% of the cancer cells. This subtype is enriched in patients with metabolic syndrome, diabetes and non-alcoholic steatohepatitis. Prognosis is similar or better than usual HCC(Salomao et al. 2010; Shibahara et al. 2014)

Clear cell HCC

Usual criterion for diagnosis is presence of cytoplasmic clearing due to glycogen and/or lipid accumulation in 50% of the cancer cells. This cutoff might be lower in other cohorts. Exclusion of renal cell carcinoma is mandatory and based on clinical information and immunohistochemistry (clear cell HCC tend to retain expression of hepatocellular markers)(Emile et al. 2001; Bannasch et al. 2017)

Fibrolamellar carcinoma

Presence of prominent intratumor fibrosis. Tumor cells have a polygonal shape and usually depict large, eosinophilic cytoplasm. Fibrolamellar carcinoma usually develops in younger patients with no clinical history of liver disease(Chagas et al. 2015; Kim et al. 2017). Some sources consider fibrolamellar carcinoma an HCC variant while others consider it a unique form of primary liver cancer(Cancer Protocol Templates. College of American Pathologists 2019; World Health Organization 2010; Chagas et al. 2015; Kim et al. 2017).

Scirrhous HCC

Presence of intratumor fibrosis in more than 50% of the tumor area. Fibrolamellar carcinoma is an important differential diagnosis, but it usually develops in younger patients with no background liver injury. Scirrhous HCC develops in older patients with cirrhosis(Kim et al. 2017; Kim et al. 2009)

Sarcomatoid HCC

Presence of multiple spindle cells in the specimen. The minimum cutoff of spindle cells for diagnosis is not established, but the high proliferative nature of these cells usually makes them the dominant population in the specimen. Expression of Vimentin is frequent(Haratake and Horie 1991; Liao et al. 2019)

Lymphoepithelioma-like HCC

Defined as poorly differentiated tumors with syncytial sheets of inflammatory cells (mostly lymphocytes). Immunohistochemistry might be useful for confirming the epithelial nature and the hepatocellular lineage of this subtype(Labgaa et al. 2017)

Massive presence of neutrophils in the tumor sinusoids. Tumors are usually poorly- to undifferentiated and may show sarcomatoid changes. This subtype tends to occur in older patients and is associated with poor prognosis(Araki et al. 2007; Kohno et al. 2013).

Macrotrabecular massive HCC

Tumors show high prevalence of macrotrabecular architecture (> 6 cells thick); a recent publication suggest a 30% cutoff for diagnosis(Jeon et al. 2019). This subtype is constantly associated with vascular invasion and presence of TP53 mutations. Prognosis is worse than usual HCC(Calderaro et al. 2017).