Background: Large granular lymphocytic leukemia (LGLL) is characterized by a clonal expansion of cytotoxic CD8+ T or NK cells. The pathogenesis of LGLL is not fully understood, highlighting a need for a deeper understanding of the disease's molecular complexities. Although peripheral blood and hematologic features are well defined, less is known about tissue infiltration and microenvironment interactions, particularly in the liver, where leukemic cells may accumulate and contribute to dysfunction. Aims: To characterize the histopathologic features of hepatic infiltration by LGLL cells in patients with underlying liver disease. Methods: We examined 16 cases of hepatic LGLL infiltration in patients with predisposing conditions including autoimmune diseases and inherited immune disorders (e.g., common variable immunodeficiency). The degree of LGLL infiltration was quantified by counting LGLL cells across three high-power fields (HPFs) using diagnostic markers (e.g., CD8, CD57) and averaging the total. Non-LGLL-related histologic changes, including fibrosis, inflammation, steatosis, cholestasis, ductular reaction, and hepatocellular degeneration, were also evaluated. Results: Nearly all patients demonstrated prominent lobular intrasinusoidal infiltration exceeding background levels, most frequently in those with marked liver enzyme abnormalities. Such infiltrates were absent in control cases. Quantitative analyses revealed correlations between LGLL and the severity of liver function test derangements. Conclusions: Significant hepatic LGLL infiltration was observed across patients with medical liver disease, encompassing αβ and γδ T-cells and NK-cell subtypes. Ongoing analyses aim to further delineate the relationship between LGLL subtype, infiltration pattern and severity, and biochemical indices of liver injury. The observed heterogeneity amongst patients underscores the diagnostic challenges of hepatic LGLL and the need for interdisciplinary collaboration among hematology, hepatology, and pathology to improve diagnosis and management.
