Flow Cytometric Characterization and Clinical Outcome of CD4+ T-Cell Lymphoma in Dogs: 67 Cases

Journal of Veterinary Internal Medicine (Impact Factor: 1.88). 02/2014; 28(2). DOI: 10.1111/jvim.12304
Source: PubMed


Canine T-cell lymphoma (TCL) is conventionally considered an aggressive disease, but some forms are histologically and clinically indolent. CD4 TCL is reported to be the most common subtype of TCL. We assessed flow cytometric characteristics, histologic features when available, and clinical outcomes of CD4+ TCL to determine if flow cytometry can be used to subclassify this group of lymphomas.
To test the hypothesis that canine CD4+ T-cell lymphoma (TCL) is a homogeneous group of lymphomas with an aggressive clinical course.
Sixty-seven dogs diagnosed with CD4+ TCL by flow cytometry and treated at 1 of 3 oncology referral clinics.
Retrospective multivariable analysis of outcome in canine CD4+ TCL including patient characteristics, treatment, and flow cytometric features.
The majority of CD4+ TCL were CD45+, expressed low class II MHC, and exhibited an aggressive clinical course independent of treatment regimen (median survival, 159 days). Histologically, CD4+ TCL were classified as lymphoblastic or peripheral T cell. Size of the neoplastic lymphocytes had a modest effect on both PFI and survival in this group. A small number of CD4+ TCL were CD45- and class II MHC high, and exhibited an apparently more indolent clinical course (median survival not yet reached).
Although the majority of CD4+ TCL in dogs had uniform clinical and flow cytometric features and an aggressive clinical course, a subset had a unique immunophenotype that predicts significantly longer survival. This finding strengthens the utility of flow cytometry to aid in the stratification of canine lymphoma.

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Available from: Paul S Morley, Sep 02, 2015
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    • "This antigen plays a role in various biological activities, including regulation of different stages of lymphocyte maturation, activation, and proliferation (Dahlke et al., 2004). Recently, less aggressive or indolent forms of canine lymphoma have been described and these indolent lymphomas may be associated with the loss of CD45 expression (Aresu et al., 2013; Avery et al., 2014; Seelig et al., 2014). Canine lymphoid neoplasms submitted for immunophenotyping at the North Carolina State University College of Veterinary Medicine exhibit varying degrees of CD45 surface expression. "
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    ABSTRACT: Please cite this article in press as: Fogle, J.E., et al., CD45+ and CD45− lymphocyte populations identified by flow cytometry from dogs with lymphoma exhibit similar morphology and the same clonal (B cell or T cell) lineage. Vet. Immunol. Immunopathol. (2015), a b s t r a c t Flow cytometric analysis of canine lymphoma sometimes demonstrates a mixed population of CD45+ and CD45− lymphocytes. Recently, indolent forms of canine lymphoma have been described which are associated with the loss of CD45 expression, warranting further investigation of the role of CD45 in canine lymphoma. The purpose of this study was to compare morphology and assess clonal origin between CD45+ and CD45− lymphocyte populations identified by flow cytometry in confirmed cases of canine Band T-cell lymphoma. Our hypothesis was that the CD45− population of lymphocytes represented a phenotypic variant of the CD45+ population. Fifteen client-owned dogs with lymphoma and distinct CD45+ and CD45− lymphocyte populations identified by flow cytometry were identified for a blinded, prospective assessment of morphology and clonal origin (B cell or T cell) between populations of sorted CD45+ and CD45− cells. Lymphocytes were isolated from 11 dogs for paired cytologic evaluation. In 10/11 dogs, the CD45+ and CD45− samples were similar (95% C.I., 0.301–1.00). DNA was harvested from sorted populations of CD45+ and CD45− cells from 12/15 dogs and PARR analysis produced amplicons of identical size from both populations, indicating that 100% (12/12) were of the same lineage, B cell or T cell (95% C.I., 0.757–1.00). Collectively, our data suggests that the CD45− population identified in dogs with lymphoma represents a phenotypic variant of the CD45+ population.
    Veterinary Immunology and Immunopathology 10/2015; DOI:10.1016/j.vetimm.2015.10.004 · 1.54 Impact Factor
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    ABSTRACT: Classification of types of lymphomas is done by interpreting cell morphology results obtained in cytological and/or histological examinations. In recent years, additional methods like immunocytochemistry (ICC), immunohistochemistry (IHC), immunophenotyping by flow cytometry and polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR), have been used to diagnose and classify lymphomas. Unfortunately, none of these methods is completely specific and sensitive. Thus, a combination of several diagnostic methods or use of all available techniques allows for evaluation of morphological properties of cells like their maturity and diversification. Owing to the use of sets of antibodies it is possible to identify the phenotype of hyperplastic cells as well as their origin. Combination of results obtained through phenotypical analysis with flow cytometry examination with morphological, histological and genetic testing enables a detailed analysis of in this case, lymphoproliferative diseases including reaction changes, primary and secondary immunological deficits as well as autoimmune diseases.
    Central-European Journal of Immunology 01/2014; 3(3):327-330. DOI:10.5114/ceji.2014.45943 · 0.28 Impact Factor
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    ABSTRACT: Background Canine T-cell lymphoma (TCL) is clinically and histologically heterogeneous with some forms, such as T-zone lymphoma (TZL), having an indolent course. Immunophenotyping is an important tool in the classification of TCL in people, and can be equally useful in dogs.Hypothesis/Objectives We hypothesized that loss of expression of the CD45 antigen is a specific diagnostic feature of TZL.AnimalsTwenty dogs with concurrent histology and immunophenotyping by flow cytometry were studied in depth. An additional 494 dogs diagnosed by immunophenotyping were used to characterize the population of dogs with this disease.Methods Lymph node biopsies from 35 dogs with TCL were classified by 2 pathologists using WHO criteria. Twenty lymph nodes were from dogs with CD45− TCL and 15 were from CD45+ TCL. The pathologists were blinded to the flow cytometry findings. Outcome information was sought for the 20 dogs with CD45− lymphoma, and population characteristics of the additional 494 dogs were described.ResultsAll 20 CD45− cases were classified as TZL. The 15 CD45+ cases were classified as aggressive TCL and are described in an accompanying paper. TZL cases had a median survival of 637 days. Examination of 494 additional dogs diagnosed with TZL by immunophenotyping demonstrated that 40% of cases are in Golden Retrievers, are diagnosed at a median age of 10 years, and the majority have lymphadenopathy and lymphocytosis.ConclusionsTZL has unique immunophenotypic features that can be used for diagnosis.
    Journal of Veterinary Internal Medicine 03/2014; 28(3). DOI:10.1111/jvim.12343 · 1.88 Impact Factor
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