Intraepithelial cytotoxic lymphocytes are associated with a poor prognosis in feline intestinal T-cell lymphoma

Abstract

The expression of cytotoxic molecules in feline intestinal T-cell lymphoma cells was examined immunohistochemically using endoscopic samples of 50 cases. Cases included 14 large-cell lymphomas (LCLs) and 36 small-cell lymphomas (SCLs). Most LCL and some SCL exhibited marked erosion and villous atrophy. Clonal T-cell receptor (TCR) gene rearrangement was detected in 10/14 (71%) LCL cases and 33/36 (92%) SCL cases. No clonal immunoglobulin heavy chain (IgH) gene rearrangement was detected. Immunohistochemically, all cases were positive for CD3 and negative for CD79α, CD30, CD56, and Foxp3. LCLs were positive for CD8 in 13/14 cases (93%), T-cell intracellular antigen 1 (TIA1) in 14/14 cases (100%), and granzyme B in 6/14 cases (43%). SCLs were positive for CD8 in 28/36 cases (78%), TIA1 in 33/36 cases (92%), and granzyme B in 2/36 cases (6%). TIA1- and granzyme B-positive neoplastic lymphocytes were predominantly observed in the mucosal epithelium of 10/50 cases (20%) and 6/50 cases (12%), respectively. No significant differences in survival time were found based on cell size or epitheliotropism. However, cases with TIA1+ and/or granzyme B+ neoplastic lymphocytes predominantly in the mucosal epithelium had significantly shorter survival times ( P < .05), suggesting that mucosal epithelium infiltration of neoplastic cells with a cytotoxic immunophenotype is a negative prognostic factor. Therefore, intraepithelial cytotoxic lymphocytes may be associated with mucosal injury and impaired intestinal function, leading to a poor prognosis in cats with intestinal T-cell lymphoma.

ACVIMconsensus statement guidelines on diagnosing and distinguishing low‐grade neoplastic from inflammatory lymphocytic chronic enteropathies in cats

“…Recent studies investigated additional diagnostic and prognostic markers including TIA1 cytotoxic granule‐associated RNA binding protein and S100/Calgranulin. The presence of intraepithelial TIA1 + cytotoxic lymphocytes was associated with poor prognosis in cats with LGITL 166 ; S100/Calgranulin was not discriminant between LGITL and LPE 94 …”

Application of automated machine learning for histological evaluation of feline endoscopic samples

“…In a previous study, cytotoxicity of neoplastic lymphocytes had a relationship with the survival times in feline intestinal T-cell lymphoma [ 6 ]. In experiment 3, the model classified intestinal T-cell lymphoma according to the expression of GRB, which is cytotoxic granules.…”

“…In experiment 1, a model was created to distinguish between intestinal T-cell lymphoma and CE. Because the prognosis of intestinal T-cell lymphomas is associated with cell size and cytotoxicity [ 6 , 14 ], two models that classify intestinal T-cell lymphoma based on cell size and cytotoxicity were created respectively in experiment 2 and 3. In experiment 4, a model was created to predict T-cell receptor (TCR) clonality analysis results from histology images.…”

Intraepithelial lymphocytes are associated with epithelial injury in feline intestinal T-cell lymphoma

“…Therefore, clinically, LCL is a high-grade lymphoma and SCL is a low-grade lymphoma. In our previous study, the median survival of LCL cases was shorter than that of SCL and cytotoxicity of intraepithelial lymphocytes is a poor prognostic factor in FITL [ 18 ]. However, the effect of cytotoxic lymphocytes on mucosal epithelium is still unknown.…”

“…Enteropathy-associated T-cell lymphoma is associated with celiac disease in humans [ 29 ]. Intraepithelial lymphocytes, which is commonly seen in FITL [ 18 ], are believed to play an important role in the destruction of epithelial cells in human enteropathy-associated T-cell lymphoma and celiac disease [ 19 , 29 , 32 ]. Some intraepithelial lymphocytes in celiac disease and enteropathy-associated T-cell lymphoma express granzyme B (GRB), which induces apoptosis of target cells by the cell death pathway and leads to epithelial injury and villous atrophy [ 2 , 4 , 8 , 9 , 28 , 29 ].…”