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Feline low-grade intestinal T cell lymphoma: a unique natural model of human indolent T cell lymphoproliferative disorder of the gastrointestinal tract

Abstract

Indolent T cell lymphoproliferative disorder (LPD) of the gastrointestinal tract (GI-TLPD) is a rare human primary gastrointestinal T cell lymphoma that was recently included in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Low-grade intestinal T cell lymphoma (LGITL), an emerging disease in the domestic cat, shares a number of features with human GI-TLPD. In this prospective study, we determined whether feline LGITL might serve as a model of human GI-TLPD. We analyzed clinical, laboratory, and radiological data and performed histopathological and molecular studies on small intestinal biopsies from 22 domestic cats diagnosed with LGITL. This cancer mostly affects aging cats, is associated with nonspecific gastrointestinal tract signs, and is usually characterized by an indolent course. A histopathological analysis indicated that LGITL was mainly located in the jejunum. The small intestinal lamina propria was infiltrated by large numbers of small CD3+ T cell lymphocytes with various CD4 and CD8 expression profiles (CD4+ CD8− (4 out of 11, 36%), CD4− CD8+ (3 out of 11, 27%), and CD4− CD8− (4 out of 11, 36%)). Intraepithelial lymphocyte (IEL) counts were elevated in all cases. Ki67 was expressed in lamina propria lymphocytes and IELs at a low level (<30%). Most LGITLs were labelled by antibodies against phosphorylated STAT5, but were negative for CD56 and phosphorylated STAT3. T cell receptor gamma chain gene monoclonality was found in 86% of cases. These findings confirmed that feline LGITL shares clinical and histopathological features with human GI-TLPD. Feline LGITL may therefore constitute a relevant model of the human disease.

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Fig. 1: Hematoxylin and eosin (H&E), CD3, and Ki67 immunohistochemical staining in feline LGITL.
Fig. 2: CD4, CD8, and CD56 immunohistochemical staining in feline LGITL.
Fig. 3: CD3, pSTAT3, and pSTAT5 immunohistochemical staining in two representative cases of feline LGITL (C2 and C8).
Fig. 4: A new model of lymphomagenesis in indolent GI-TLPD.

Data availability

The authors confirm that all data generated or analyzed during this study are included in this published article and its Supplementary information files.

Author contributions

VF, LC, JB, and OH initiated, designed, and supervised the study. VF included patients, collected clinical and laboratory data, and assisted surgeons with intestinal biopsies. JB, HH, and NC conducted histopathological analyses. MET performed clonality analysis. JB, TJM, MET, EM, HH, and NC interpreted histology, immunohistochemistry, and clonality data. VF, MVP, HH, LC, JB, and NC analyzed the data and drafted the manuscript. VF, LC, HH, MVP, GM, TJM, NC-B, MET, EM, NC, OH, and JB reviewed the manuscript. All the authors read and approved the final version.

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Acknowledgements

We thank the Department of Surgery at Alfort Veterinary School Hospital (Maisons-Alfort, France) for its contribution to the surgical procedures, Dr. Jeremy Beguin for his contribution to earlier clinical data collection, and Pr. Maxence Delverdier and Dr. Marie Odile Semin for the preliminary histopathological analyses.

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Correspondence to Lucile Couronné.

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This study was approved by the investigational review board at Alfort National Veterinary School (COMERC, Maisons-Alfort, France; reference: 2017-05-09).

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Freiche, V., Cordonnier, N., Paulin, M.V. et al. Feline low-grade intestinal T cell lymphoma: a unique natural model of human indolent T cell lymphoproliferative disorder of the gastrointestinal tract. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00581-x

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