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Using lymphoma subtypes to predict clinical outcome in cats?

Wolfesberger B, Skor O, Hammer SE, et al. (2016). Does categorisation of lymphoma subtypes according to the World Health Organization classification predict clinical outcome in cats? J Feline Med Surg. 2016 Aug 30.

Lymphoma the most common type of cancer in domestic cats. It is also a common disease in humans, dogs, and other species. While in humans lymphoma is almost always sub-typed through the use of ore advanced laboratory techniques, in feline medicine the diagnosis is often left as “lymphoma”.  Sub-typing lymphoma is of vital importance in human medicine, as treatment and prognosis are both altered by the specific variety of cancer.

In veterinary medicine there is less utility to sub-typing, leading to a catch-22; veterinarians and pet owners are less willing to pay for testing without clinical utility, however without this information it is difficult to determine if there are changes to treatment and prognosis. As techniques such as immunohistochemistry (IHC), immunocytochemistry (ICC) and flow cytometry (FC) become more readily available and inexpensive, subtyping lymphoma is becoming more common in feline medicine.

This paper attempted to determine which subtypes of lymphoma naturally occur in cats according to the World Health Organization (WHO) classification system; and to assess if these subtypes carried any prognostic value.

Cases were recruited from cats presenting to the University of Veterinary Medicine Vienna over a 12 year period for treatment of lymphoma. Cases were confirmed by histology and treated with chemotherapy (usually COP or L-CHOP), radiation, or both, and had full records available. While 544 cats were identified with lymphoma in this time period, only 30 met all inclusion requirements.  47% of cases were alimentary, 43% other extranodal, and 10% nodal.

IHC was performed on samples using CD3 as a pan T cell marker and CD79a as a pan B cell marker. Clonality assays for V-J recombination were used if IHC was unsuccessful. Mitotic rates and grades were determined by pathologists.

Sex, glucocorticoid pretreatment, anatomical form, IHC, histopathological subtype, grade, radiation, and surgery were analyzed for affects on survival.

Two thirds of cats had T-cell lymphoma with only one third B-cell. There has been significant debate in previous reports as to whether B or T cell lymphomas predominate in cats, with some suggestion that T cell corms may be more associated with retroviral infection.  Representatives of each of the 8 WHO lymphoma subtypes were identified.  Alimentary lymphoma was the most common anatomical location.

Cats with T-cell rich B-cell lymphoma (TCRBCL) or intestinal T-cell lymphoma (ITCL) had significantly longer survival times than cats with diffuse large B-cell lymphoma (DLBCL). Conversely, cats with peripheral T-cell lymphoma (PTCL) had much shorter survivals with those with ITCL.   Some diseases, such as T cell rich B cell lymphoma and diffuse large B cell lymphoma, may appears very similar in histological and biological behaviour, and yet carry at 1y difference in median survival.

Cats with alimentary lymphoma survived significantly longer than those with extranodal forms (7.1 vs 2.2 months). In general, B-cell vs T-cell lymphoma did not carry a difference in survival time.

Pre-treatment with glucocorticoids had no effect on survival. This is contrary to some previous reports, which may be due to small sample sizes.  Radiation therapy also did not seem to confer a survival benefit, however small patient numbers and a lack of matched comparisons makes interpretation of this finding difficult.

Interestingly, the authors of this paper did not qualify retroviral status of these cats, which is a potential shortcoming of this paper, as FeLV status in particular is a well known negative prognostic factor for feline lymphoma.

This paper suffers from several limitations, not the least of which is the small samples size. As many subtypes had only 1-2 cats represented, there are many effects that may have altered survival times and larger studies are needed to confirm these results. However, this provided invaluable basic information on the effects of lymphoma subtyping on treatment and survival. (MRK)

See also:
Pohlman LM, Higginbotham ML, Welles EG, et al. Immunophenotypic and histologic classification of 50 cases of feline gastrointestinal lymphoma. Vet Pathol 2009; 46: 259–268.