Bone marrow necrosis and myelophthisis: manifestations of T‐cell lymphoma in a horse

Abstract: A 14‐year‐old spayed American Paint mare was evaluated for mild colic, anorexia, pyrexia, and pancytopenia. Physical examination revealed mild tachycardia, tachypnea, and pale mucous membranes. Serial laboratory analyses revealed progressive pancytopenia, hyperfibrinogenemia, and hyperglobulinemia. A few large atypical cells were observed in peripheral blood smears. Results of tests for equine infectious anemia and antipenicillin antibody were negative. Serum protein electrophoresis indicated a polyclonal gammopathy. Smears of bone marrow aspirates contained hypercellular particles, but cell lines could not be identified because the cells were karyolytic, with pale basophilic smudged nuclei and lack of cellular detail. A diagnosis of bone marrow necrosis was made. Treatment consisted of antimicrobials, nonsteroidal anti‐inflammatory drugs, and corticosteroids. The pyrexia resolved; however, the pancytopenia progressively worsened and petechiation and epistaxis developed. The horse was humanely euthanized. Postmortem examination revealed a diffuse round cell neoplasm infiltrating the kidneys, spleen, lymph nodes, lungs, and bone marrow. Immunophenotyping results (CD3+, CD79α−) indicated the neoplastic cells were of T‐cell lineage. Infiltration of lymphoma cells into the bone marrow appeared to have resulted in severe myelophthisis and bone marrow necrosis. Bone marrow necrosis has been associated previously with lymphoma in humans and dogs. To our knowledge, this is the first reported case of lymphoma resulting in bone marrow necrosis in a horse.     

Expression of P-glycoprotein and breast cancer resistance protein in three cases of canine lymphoma showing drug resistance

In canine lymphoma, drug resistance is the major factor hindering treatment. In this study, we performed immunohistochemical examination of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which are considered as transporters related to multidrug resistance in three recurrent canine lymphomas. All cases were negative for both transporters before anticancer drug administration, but became positive after this administration. The expression was confirmed in capillary endothelial cells, such as in brain capillaries acting as the blood-brain barrier (BBB). It is suggested that both transporters expressed on capillary endothelial cells in lymphoma tissue may inhibit the spread of anticancer drugs into tumor tissues from blood, the same as the BBB. Therefore, capillary endothelial cells could act as a blood-tumor barrier, which might be involved in drug resistance in canine lymphoma.     

Differences in the geographic distribution of lymphoma subtypes in Golden retrievers in the USA

The purpose of this cross‐sectional study was to examine differences in the geographic distribution of two distinct subtypes of canine lymphoma (CL), B‐cell lymphoma (BCL) and T‐zone lymphoma (TZL), in the USA while accounting for heritable risks associated with the outcome of disease through inclusion of only one breed of dog. This study included 454 Golden retrievers and associations between geographic areas of the USA and the phenotypic variant of lymphoma were examined using multivariable logistic regression. There was a detectable difference in the geographic distribution of BCL and TZL with dogs in the Northeast [odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.6–7.0] and East North Central regions (OR = 12.1, 95%CI = 3.6–40.5) being more likely to be diagnosed with TZL as compared to dogs in the Mountain region of the USA. The finding of non‐random geographic distribution of lymphoma subtypes suggest that environmental risk factors may contribute to the development of different types of CL.     

Immunophenotypic and histological characterisation of 109 cases of feline lymphosarcoma

OBJECTIVE: To determine and analyse the immunophenotype and histological appearance of naturally occurring cases of lymphosarcoma in Australian cats. DESIGN: A prospective multi-institutional study of naturally occurring feline lymphosarcoma. METHODS: One hundred and eighteen cats were referred for diagnosis and/or management of suspected lymphosarcoma. Tissue samples for histopathological analysis and immunophenotyping were collected as biopsies or at necropsy from 109 cases. Histological classification of the neoplasms followed the Working Formulation Classification System. Four multi-species cross-reactive antibodies were used to classify tumours as having a B or T cell phenotype. RESULTS: Seventy-six (70%) cases were B cell tumours and 28 (26%) were T cell tumours. The remaining 5 (4%) specimens failed to stain with the four antibodies. Histologically, 11 (10%) cases were classified as low-grade, 72 (66%) were medium-grade and 26 (24%) were high-grade tumours. There were no significant associations between age and either histological grade or immunophenotype. Mediastinal and leukaemic cases were significantly more likely to be T cell tumours (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: In contrast to previously documented studies in the cat, the majority of cases of lymphosarcoma were of B cell phenotype and intermediate histological grade. Based on our data, the histological phenotype of lymphosarcoma is unlikely to predict immunotype, nor are cases of certain immunotypes likely to be of specific histological subtype. Considered in relation to previous reports, the findings suggest that epidemiological factors operating in these cats to produce lymphosarcoma may be different to those operating in North American and UK cat populations.     

Canine CD4+ T‐cell lymphoma identified by flow cytometry exhibits a consistent histomorphology and gene expression profile

T‐cell lymphomas (TCL) are a diverse group of neoplasms with variable diagnostic features, pathophysiologies, therapeutic responses and clinical outcomes. In dogs, TCL includes indolent and aggressive tumours such as T‐zone lymphoma (TZL) and peripheral T‐cell lymphoma (PTCL), respectively. Delineation of molecular subtypes and investigation into underlying pathophysiologies of aggressive TCLs remains inadequate. We investigate the correlations between flow cytometry and histopathology of 73 cases of nodal TCL. The majority of cases (82.2%) were characterized as CD4⁺ TCL by flow cytometry. Fewer cases were classified as CD8⁺ TCL (6.8%) or CD4^?CD8^? TCL (11.0%). All cases, regardless of immunophenotype, exhibited conserved histologic features consistent with the WHO classification of PTCL. Histologic subsets of PTCL corresponding to immunophenotypic features were not identified. Neoplastic cell size determined by flow cytometry correlated significantly with mitotic rate. RNA‐seq was performed on a subset of CD4⁺ PTCL cases (n = 6) and compared with sorted control CD4⁺ T‐cells. The gene expression pattern of CD4⁺ PTCL was similar between all cases regardless of breed. PTCL was enriched in pathways representing G‐coupled protein receptor signalling, extracellular matrix remodelling and vascular development, immune signalling and mitotic activity. Furthermore, global gene expression changes were consistent with downregulation of PTEN signalling and upregulation of the MTOR‐PI3K‐ATK axis. In this study, we evaluated the correlations between flow cytometry, histopathology and gene expression within a large cohort of nodal TCLs. We further demonstrate the ability of flow cytometry to identify a subtype of T‐cell lymphoma, CD4+ PTCL, with a uniform histomorphology and gene expression profile.