Canine T-zone lymphoma: unique immunophenotypic features, outcome, and population characteristics

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.

Animals: Twenty 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.

Results: All 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.

Conclusions: TZL has unique immunophenotypic features that can be used for diagnosis.

Keywords: Flow cytometry; Golden retriever; Leukemia.

Figure 1

Immunophenotypic features of cells from patients with TZL. (A) Plot of a lymph node aspirate demonstrating the CD45+ (purple) and CD45− T cells (green). The cells in red are B cells (as determined by expression of CD21, but not CD5, plot not shown) and are shown for comparison of CD21 expression. (B) Representative plots of cell size, CD21 expression, class II MHC expression, and CD25 expression on CD45− and CD45+ T cells in the same patient using color gates described in A. The histograms are scaled so that populations with different cell numbers can be compared, so the Y axis does not have units. B‐cell expression of CD21 is shown (red), but not B‐cell expression of class II MHC or CD25. (C) Summary data for all cases assessed with the multicolor panel. Each plot shows the level of expression of the indicated parameter in CD45+ and CD45− cells determined in the same dog, and the values for an individual dog are joined by lines. All parameters are mean fluorescence intensity except for CD25 expression, which is a percentage of positive cells. All comparisons between neoplastic and nonneoplastic cells were statistically significant (P < .05) as determined by the Wilcoxon signed‐rank test applied to the difference in log median fluorescence (class II MHC and CD21), the difference in percent positive (CD25), or the ratio of the linear forward scatter value (size).

Figure 2

The histologic and immunohistologic features of canine T‐zone lymphoma (TZL). Lymph node tissue is from a 9‐year‐old Shih Tzu breed with TZL, which demonstrates light microscopic (A,B) (hematoxylin and eosin (H&E)‐stained) and immunohistochemical (C,D) features representative of all 13 cases. In A, note the thinned nodal capsule and the compressed remnant fading follicles (black arrows) owing to the eccentric population of proliferating cells. Higher magnification view of A reveals a proliferating population of small cells with abundant, clear cytoplasm and oval nuclei with frequent, sharp, shallow indentations (B, white arrows). Immunohistochemistry confirms the T‐cell phenotype of the proliferating population through uniform, heavy CD3‐immunoreactivity (C, brown) and absent Pax5 immunoreactivity (D, red). However, note the heavy Pax5‐immunoreactivity in the residual, compressed follicular B cells (D, red). E and F show normal lymph nodes stained for Pax5 (E) and CD3 (F) for comparison. Bars: B = 25 μm, C,D = 300 μm.