Flow cytometric characterization and clinical outcome of CD4+ T-cell lymphoma in dogs: 67 cases

Abstract

Background: 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.

Objective: To test the hypothesis that canine CD4+ T-cell lymphoma (TCL) is a homogeneous group of lymphomas with an aggressive clinical course.

Animals: Sixty-seven dogs diagnosed with CD4+ TCL by flow cytometry and treated at 1 of 3 oncology referral clinics.

Methods: Retrospective multivariable analysis of outcome in canine CD4+ TCL including patient characteristics, treatment, and flow cytometric features.

Results: 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).

Conclusions and clinical importance: 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.

Keywords: Canine; Immunophenotyping; Lymphoblastic; Peripheral T cell; Prognosis.

Figure 1

Typical flow cytometric properties of CD4+/CD45+ (A) and CD4+/CD45− (B) subsets of CD4+ lymphoma. CD45 expression is shown in the right panel. CD45− cases expressed high levels of class II MHC compared with CD4+/CD45+ dogs (left panel), and higher levels of CD21 (middle panel).

Figure 2

Surface marker expression distinguishes CD4+ lymphomas with distinct clinical courses. Median PFI/survival CD4+/CD45+ = 91/159 days, CD4+/CD45− = undefined/undefined days.

Figure 3

Progression‐free interval (PFI) is not different between treatment groups. Overall survival is significantly different for prednisone only compared with CHOP. Only dogs with CD4+/CD45+ lymphoma were included in this analysis.

Figure 4

Histologic and immunohistologic features of the 2 morphologic variants of canine CD4+/CD45+ lymphoma. Five of the 15 cases of CD4+/CD45+ lymphoma were histologically classified as lymphoblastic T‐cell lymphoma (LBT, A–C), whereas 10 were classified as peripheral T‐cell lymphoma (PTCL, D–F). On hematoxylin‐and‐eosin–stained sections, cases of LBT (A) were characterized by diffuse effacement of the lymph node architecture by intermediate‐sized cells with uniform round‐to‐oval nuclei and high numbers of mitotic figures, whereas in PTCL (B), the effacing cells were intermediate‐to‐large in size with irregularly shaped nuclei, anisokaryosis, and rare mitotic figures. In both LBT and PTCL, immunohistochemistry confirms the T‐cell phenotype of the neoplastic cells through uniform, heavy anti‐CD3 immunoreactivity (B and E, red) and absent‐to‐scant anti‐Pax5 (C, red) or CD79a (F, red) immunoreactivity.