Immunophenotyping of intraepithelial lymphocytes in canine chronic enteropathy and intestinal T-cell lymphoma using...

Human enteropathy-associated T-cell lymphoma (EATL) is considered to be derived from intraepithelial lymphocytes (IELs); however, the origin of canine intestinal T-cell lymphoma (ITCL) remains unclear. Histological, immunohistochemical, and clonality examinations were performed using endoscopically collected canine duodenum samples of mucosal lesions of chronic enteropathy (CE; 73 cases) and ITCL without transmural neoplastic mass lesions (64 cases). Histopathological examinations revealed the intraepithelial accumulation of lymphocytes (called "intraepithelial lymphocytosis") in 54/73 CE cases (74%) and the epitheliotropism of neoplastic lymphocytes in 63/64 ITCL cases (98%). Immunohistochemically, IELs in CE with intraepithelial lymphocytosis (IEL⁺CE) were diffusely immunopositive for CD3, with scattered immunopositivity for CD5, CD8, CD20, and granzyme B (GRB). The percentage of CD8⁺ in CD3⁺ IELs was significantly lower in IEL⁺CE than in CE without intraepithelial lymphocytosis (IEL^-CE). Double-labeling immunohistochemistry revealed a high percentage of GRB expression in CD8^- IEL among IEL⁺CE. Among 64 ITCL cases, CD3 was immunopositive in 64 (100%), CD5 in 22 (34%), CD8 in 8 (13%), CD20 in 12 (19%), CD30 in 13 (20%), and GRB in 49 (77%). In CD3⁺ cells, Ki67 immunopositivity was highest in ITCL, intermediate in IEL⁺CE, and lower in IEL^-CE. A clonal TCR gene rearrangement was detected in 1/19 IEL^-CE cases (5%), 15/54 IEL⁺CE (28%), and 38/58 ITCL (66%). These results indicate that the immunophenotype of canine ITCL (CD8^-GRB⁺) is similar to that of the increased IELs in CE. The high proliferative activity and clonality of T cells in IEL⁺CE suggest that canine ITCL originates from these IELs, similar to human EATL.