Patterns of Lymphocytic Infiltrates Can Differentiate Feline Hepatic Lymphoma from Lymphocytic Portal Hepatitis

SIMPLE SUMMARY: The study aimed to distinguish between two important causes of liver disease in cats: lymphocytic inflammation and lymphoma. Both conditions are characterized by infiltration of small lymphocytes, making an accurate diagnosis difficult. Since the neoplastic cells of a lymphoma are derived from a single clone, a monoclonal population indicates a neoplastic condition in contrast to a polyclonal inflammatory condition. Clonality testing is therefore commonly used to detect lymphoma. The goal of our study was to define specific visual patterns of lymphocytic infiltrates in liver biopsies of cats which are predictive of a lymphoma or inflammation. A retrospective study was performed on 44 cats’ biopsies, and the lymphocytic infiltrates were characterized and correlated with clonality results. Four patterns of lymphocytic infiltrates were characterized: (1) tightly periportal, (2) periportal and centrilobular, (3) nodular, and (4) periportal with sinusoidal extension. Sensitivity and specificity of the lymphocytic patterns to diagnose lymphomas were analyzed against clonality results. Lymphocytic patterns 2, 3, and 4 accurately diagnosed hepatic lymphomas with a sensitivity and specificity of 82% and 77%, respectively. These four patterns of lymphocyte infiltrates provide useful diagnostic information and allow more accurate differentiation of a lymphoma from inflammation. ABSTRACT: Hepatic lymphoma is poorly characterized in cats and differentiating between inflammation and lymphomas is often difficult. The diagnosis of hepatic lymphoma in humans relies on recognition of specific patterns of lymphocytic infiltrates and clonality testing of antigen receptors. Herein, we defined similar patterns of lymphocytic infiltrates in hepatic biopsies of cats and correlated them with clonality to determine which patterns are predictive of lymphoma. A retrospective study was performed on surgical biopsies from 44 cats. The immunophenotype was characterized using CD3 and CD20 on all 44 samples. All 44 samples were tested using PCR for T-cell receptor gamma-gene rearrangements. PCR for immunoglobulin heavy chain gene rearrangements was performed on 24 of these cats. Four patterns of lymphocytic infiltrates were characterized: (1) tightly periportal, (2) periportal and centrilobular, (3) nodular, and (4) periportal with sinusoidal extension. Other histomorphologic features (fibrosis, biliary hyperplasia, bile ductopenia, bile duct targeting, hepatic hematopoiesis, lipogranulomas, lymphonodular aggregates, other inflammatory cells) were also evaluated. The sensitivity and specificity of the lymphocytic patterns to diagnose lymphomas were determined using Bayesian Hui–Walter analysis (BLCM) against clonality results. Lymphocytic patterns 2, 3, and 4 accurately diagnosed hepatic lymphomas with a sensitivity and specificity of 82% (CI 95%: 0.65, 0.96) and 77% (CI 95%: 0.54, 1.00), respectively. None of the other microscopic features evaluated were predictive of a lymphoma or inflammation. Our study identified specific patterns of lymphocytic infiltration that differentiate feline hepatic lymphoma from inflammation while other histologic features were not associated with an accurate diagnosis.