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Immunophenotypic characterization and clinical outcome in cat with lymphocytosis

Rout ED, Labadie JD, Curran KM, Yoshimoto JA, Avery AC, Avery PR. Immunophenotypic characterization and clinical outcome in cats with lymphocytosis. J Vet Intern Med [Internet]. 2019 Nov 6

An increased number of circulating lymphocytes in the blood is seen in a number of conditions in cats and is a relatively common findings. Causes of lymphocytosis range from very benign (ie epinephrine mediated lymphocytosis in young cats) to more serious (ie indicators of systemic infections) to malignant (ie lymphoblastic leukemias). Despite this relative commonality, there is little data on the characterization of lymphocytosis in cats and the distribution of the various causes.

The purpose of this study was to determine the causes of lymphocytosis in cats, to characterize them via flow cytometry, and to determine if immunophenotyping is correlated with prognosis. The study was designed as a retrospective observational study of blood samples submitted to a single university diagnostic lab for immunophenotyping. All cats were >1y of age and had lymphocyte counts >6000 cells/uL.

An initial group of 146 cats were examined to define immunophenotypic categories (definition cohort) . These cats had both flow cytometry and PARR (PCR for antigen receptor rearrangement) performed. A second group of 96 cats with outcome data available were analyzed (outcome cohort). Finally, a third group of 350 cats were examined to determine immunophenotypes in a larger group of animals (concordance cohort). Signalment, PE findings, radiology results, other lab results, and survival time were all analyzed as available.

Flow cytometry was performed for CD21, CD18, CD5, CD4, and CD8. Based on these parameters, 5 major catergories of lymphocytosis were defined: heterogenous (18-23%), B-cell (16-19%), CD4+ T-cell (34-39%), double negative T-cell (7-10%), and CD5-low T-cell (13%). CD8+ T-cell lymphocytosis was uncommon (1-5%), and only one cat was double positive T-cell.

Heterogenous and B-cell phenotypes were most commonly non neoplastic and were associated with infectious conditions including FeLV, cytauxoon felis and cryptococcosis. While these cats could have significantly elevated lymphocyte counts (approaching 30000), they were statistically still lower than cats with neoplastic conditions (though significant overlap was present).

The T-cell dominant categories were largely neoplastic in origin. CD4+ T-cell lymphocytosis was associated with a prolonged survival time, and greatest survival times were seen in cats treated with a corticosteroid and chlorambucil (survival was longer than those treated with multi agent protocols). Females and animals with concurrent abdominal disease had lower survival times.  Cats with double negative T cell lymphocytosis had a poorer survival time, and those with CD5-low lymphocytosis had very poor outcomes (27 day MST).

The authors note that there is a significant presence and expansion of the double negative T-cell subset in both neoplastic and non neoplastic conditions, often approaching 1000 cells/uL. They theorize but do not confirm that these may be gamma-delta T cells.

While flow cytometry was useful to categorize these conditions, it was not always possible to determine if a lymphocytosis was neoplastic or not based on flow alone, and PARR was often required to fully characterize. However, the establishment of these categories of disease shows several clinical entities that may occur in cats and will allow greater streamlining and easier workup of feline lymphocytosis. If neoplasia is diagnosed, flow cytometry may be very useful in prognostication between various T-cell neoplasms.

A few limitations to this study were present. The retrospective nature introduces potential sources or bias, and a prospective study would be preferred. As only samples submitted for flow cytometry were included, there may have been many cats with lymphocytosis that were not further analyzed and as such are absent from the data set.  Since cats were recruited from a single lab, there may be regional various present that was not accounted for (especially when considering the possibility of infectious disease contributing to lymphocytosis. MK

See Also

Weiss DJ. Differentiating benign and malignant causes of lymphocytosis in feline bone marrow. J Vet Intern Med. 2005;19(6):855-859.

Tomiyasu H, Doi A, Chambers JK, et al. Clinical and clinicopathological characteristics of acute lymphoblastic leukaemia in six cats. J Small Anim Pract. 2018 Dec;59(12):742-746.

Workman HC, Vernau W. Chronic lymphocytic leukemia in dogs and cats: the veterinary perspective. Vet Clin North Am Small Anim Pract. 2003;33(6):1379-1399.