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Diffuse large B-cell lymphoma with DNA copy number changes in a Japanese black calf
Masaki Maezawa1,2, Ken-Ichi Watanabe3, Yoshiyasu Kobayashi3
1Laboratory of OSG Veterinary Science for Global Disease Management, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan. amaezawa@g.ecc.u-tokyo.ac.jp.
Insights
A calf was diagnosed with diffuse large B-cell lymphoma (DLBCL). DNA copy number variations were identified, suggesting a potential role in the development of this bovine lymphoma.
Area of Science:
- Veterinary Pathology
- Comparative Oncology
- Genomics
Background:
- Lymphoma is a significant neoplastic disease in cattle.
- Diffuse large B-cell lymphoma (DLBCL) is a common subtype, but its pathogenesis in young cattle requires further investigation.
- Understanding genetic alterations in bovine DLBCL can provide insights into disease mechanisms.
Purpose of the Study:
- To diagnose and characterize a case of DLBCL in a Japanese Black calf.
- To investigate potential genetic factors, specifically DNA copy number variations (CNVs), associated with the development of DLBCL in this case.
Main Methods:
- Fine needle aspiration cytology and histopathology of lymph nodes.
- Immunohistochemistry for B-cell markers (CD20, CD79α, PAX5, BLA-36) and T-cell markers (CD3, CD5).
- Hematological and serum biochemical analyses.
- DNA copy number variation analysis using comparative genomic hybridization or similar techniques.
Main Results:
- A 2-month-old calf presented with lymphadenopathy and was diagnosed with centroblastic DLBCL.
- Neoplastic cells were positive for B-cell markers and negative for T-cell markers.
- Elevated serum lactate dehydrogenase and thymidine kinase levels were observed.
- CNV analysis revealed increased copy numbers for GIMAP family genes and decreased copy numbers for GBP-1, MIR3141, OR5P1E, and PTPRG compared to healthy controls.
Conclusions:
- The study diagnosed DLBCL in a young calf, highlighting its occurrence in this age group.
- Identified specific DNA copy number variations in the affected calf.
- These CNVs may play a role in the pathogenesis of bovine DLBCL, similar to their role in human cancers.
Abstract:
A 2-month-old Japanese Black calf exhibited mandibular and superficial cervical lymph node swelling. Fine needle aspiration cytology of the superficial cervical lymph node revealed large lymphoblast-like cells with mitoses. Hematological examination revealed remarkable lymphocytosis with atypical lymphocytes. Increased activities of serum total lactate dehydrogenase and thymidine kinase were detected. At necropsy, generalized swelling of lymph nodes was observed. Histopathological analysis revealed diffuse proliferation of medium-sized round centroblastic neoplastic cells that were positive for CD20, CD79α, PAX5, and BLA-36, and negative for CD3, CD5, CD10, and CD34. The calf was diagnosed with centroblastic diffuse large B-cell lymphoma (DLBCL) based on these findings. Analysis of DNA copy number variation revealed an increased copy number for the GIMAP family relative to that in healthy cattle. Moreover, decreases in copy numbers of GBP-1, MIR3141, OR5P1E, and PTPRG relative to those in healthy cattle were also observed. Because DNA copy number variation represent a major contribution to the somatic mutation landscapes in human tumors, these findings suggest that DNA copy number changes might have contributed to the onset of DLBCL in the present case.
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