Mara S. Varvil

B‐cell leukemia is a rare form of hematologic neoplasia in sheep, especially in adult animals. We present a case report of a 5‐year‐old WhiteFace Sheep wether with suspected acute lymphoblastic leukemia. The patient, a second‐generation relative of ewes experimentally inoculated with atypical scrapie, exhibited acute lethargy and loss of appetite. Laboratory investigation revealed marked leukocytosis, lymphocytosis, and abnormal serum chemistry panel results. Microscopic examination of blood and bone marrow smears exhibited a high percentage of large neoplastic cells with lymphoid characteristics. Histopathologic analysis of the spleen, liver, lungs, and other organs confirmed the presence of widespread tissue infiltration by neoplastic cells. Immunohistochemical labeling demonstrated strong intracytoplasmic labeling for CD20, consistent with B‐cell neoplasia. Flow cytometric analysis confirmed the B‐cell lineage of the neoplastic cells. Screening for bovine leukemia virus, which can experimentally cause leukemia in sheep, yielded a negative result. In this case, the diagnosis of B‐cell leukemia was supported by a comprehensive panel of diagnostic evaluations, including cytology, histopathology, immunohistochemistry, and immunophenotyping. This case report highlights the significance of accurate diagnosis and classification of hematologic neoplasia in sheep, emphasizing the need for immunophenotyping to aid in the diagnosis of B‐cell leukemia. It also emphasizes the importance of considering spontaneous leukemia as a differential diagnosis in sheep with lymphoid neoplasia, especially in the absence of circulating infectious diseases.