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Introduction: CD80, a co-stimulatory molecule required for optimal T cell activation, is expressed on antigen-presenting cells, including monocytes and dendritic cells, in dogs and humans. We hypothesized that CD80 would be expressed on tumor cells in dogs from acute myeloid leukemia (AML) but not dogs with lymphoid neoplasms. Methods and results: We first evaluated the cellular staining pattern of a hamster anti-murine CD80 antibody (clone 16-10A1, ThermoFisher Scientific Cat# 17-0801-82, RRID: AB_469417) in blood and bone marrow aspirates from healthy dogs. Using flow cytometric analysis and examination of modified Wright's-stained cytologic smears of unsorted and flow cytometric or immunomagnetic bead-sorted leukocytes, we show that the antibody binds to mature and immature neutrophils and monocytes, but not lymphocytes or eosinophils, in blood and bone marrow. We then added the antibody to routine flow cytometric panels for immunophenotyping hematopoietic neoplasms in dogs. We found that the antibody labeled tumor cells in 72% of 39 dogs with AML and 36% of 11 dogs with acute leukemia expressing lymphoid and myeloid markers ("mixed lineage") but none of the dogs with B (n = 37) or T (n = 35) lymphoid neoplasms. A higher proportion of tumor cells in dogs with AML were labeled with the anti-CD80 antibody vs antibodies against other myeloid-associated antigens, including CD4 (36%, p = 0.003), CD11b (44%), CD11c (46%), CD14 (38%, p = 0.006) and CD18 (59%, clone YFC118). In contrast, antibodies against CD11b and CD11c bound to tumor cells in 8-32% of the lymphoid neoplasms. Discussion: We show that CD80, as detected by antibody clone 16-10A1, is a sensitive and specific marker for AML and would be useful to include in flow cytometric immunophenotyping panels in dogs.

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This article summarizes the current applications of flow cytometry in clinical veterinary medicine, which is largely restricted to the diagnosis of hematopoietic neoplasms (lymphomas and leukemias) of domestic dogs, cats, and horses. A brief background on the technique of flow cytometry and fundamentals of data interpretation are included. Major emphasis is placed on clinical indications for flow cytometry, principles of sample collection and submission, and awareness of diagnostic and prognostic utility. Expectations regarding both the benefits and limitations of flow cytometry in a clinical setting, and its complementary nature with other types of testing, are also reviewed.

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A 7-year-old castrated male domestic shorthair cat was presented for evaluation of decreased appetite and respiratory signs. A CBC run on presentation revealed severe nonregenerative anemia, thrombocytopenia, and leukocytosis characterized by a prominent population of blasts, having morphologic features suggestive of a monocytic lineage. The cat tested positive for FIV, FeLV, Mycoplasma haemominutum, and only mild abnormalities were identified on the chemistry panel. Bone marrow biopsies were obtained to investigate the bicytopenia and the possibility of a hematopoietic neoplasm. Although the bone marrow aspirate was nondiagnostic, the core biopsy was markedly hypercellular with a population of blasts, largely replacing the normal hematopoietic tissue. Immunohistochemical staining revealed that the blasts were CD3-negative, Pax5-negative, dimly CD18-positive, and moderately positive for Iba1. These findings, in addition to the prominent monocytic differentiation seen in peripheral blood, supported a diagnosis of acute monocytic leukemia. Palliative antiviral and antibiotic treatment and blood transfusion were performed. The patient was discharged on his fourth day of hospitalization. However, 15 days following discharge, the cat was euthanized due to the worsening of his systemic signs. This report discusses the classifications of myeloid leukemias, implications of infectious diseases in the pathogenesis of neoplasia in cats, and the use of Iba1, a "pan-monocytic/histiocytic" marker, in the diagnosis of acute leukemia.

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O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias após ao início do tratamento com hidroxiureia.

The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patient's anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.

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O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias

The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patient’s anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.

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Hematopoietic neoplasia other than lymphoma and leukemia is uncommon among non-human primates. Herein, we provide the first evidence of occurrence of leukemic histiocytic sarcoma in a captive common squirrel monkey with Saimiriine Gammaherpesvirus 2 (Rhadinovirus), Saimiri sciureus lymphocryptovirus 2 (Lymphocryptovirus), and Squirrel monkey retrovirus (ß-Retrovirus) coinfection.

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A 5-y-old female Golden Retriever was presented with a 2-wk history of hyporexia, vomiting, diarrhea, lethargy, weight loss, polyuria, and polydipsia. Clinical examination and ultrasonography revealed multiple organ enlargement with gallbladder and kidney nodules suggestive of disseminated neoplasia. Hematologic and biochemical analyses revealed pancytopenia, hypercalcemia, and monoclonal IgA gammopathy suspicious for a plasma cell neoplasm. Bone marrow and blood smear examination revealed neoplastic atypical cells highly suggestive of lymphoid origin. Autopsy confirmed the presence of homogeneous white masses and multifocal pale infiltrates in the spleen, kidney, small intestine, gallbladder, and urinary tract. Histologic features were consistent with a multicentric atypical plasma cell tumor. Tumor cells were negative for CD204, IBA-1, E-cadherin, CD3, CD5, CD79a, CD20, and PAX5, and positive for MUM1, consistent with plasma cell origin. The presence of > 20% of circulating blastic plasma cells was consistent with primary plasma cell leukemia with plasmablastic morphology, a disease rarely described in veterinary medicine.

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Acute myeloid leukemia is an uncommon hematopoietic neoplasm of dogs that should be differentiated from lymphoid neoplasms, such as lymphoma, because of different treatment protocols and a worse prognosis. Thoracic radiography is performed frequently in dogs with suspected hematopoietic neoplasia, and detecting a mediastinal mass often prioritizes lymphoma as the most likely diagnosis. However, we have observed a mediastinal mass in several dogs with acute myeloid leukemia and hypothesized that (1) the frequency of a mediastinal mass was higher and (2) the size of the mass was larger in dogs with acute myeloid leukemia compared to dogs with lymphoid neoplasms. In this analytical study (observational, retrospective, and cross-sectional), the sample population included 238 dogs with hematopoietic neoplasia. These dogs were divided into lymphoid (large cell lymphoma, acute lymphoblastic leukemia) and myeloid groups based on standard phenotyping tests. A mediastinal mass was detected during thoracic radiography in 73/218 (33%) and nine of 20 (45%) dogs in the lymphoid and myeloid groups (P = 0.21), respectively. The median size ratio of mediastinal mass to cardiac silhouette was 0.20 and 0.23 in the lymphoid and myeloid groups (P = 0.96), respectively. Additionally, we observed normal thoracic radiographs in 111/218 (51%) dogs in the lymphoid group and nine of 20 (45%) dogs in the myeloid group. In conclusion, acute myeloid leukemia should be considered when a mediastinal mass is detected during radiography in dogs with suspected hematopoietic neoplasia-but the presence or size of a mediastinal mass does not differentiate between myeloid and lymphoid neoplasms.

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Kidney injury can be a complication of hematopoietic neoplasia by both direct and indirect mechanisms. Virtually all lymphomas and plasma cell dyscrasias can show kidney involvement, including parenchymal infiltration and by secondary injury. Recently, a unique form of glomerulonephritis with masked monotypic immunoglobulin deposits has been reported, which shows frequent association with hematopoietic neoplasia and a propensity for progressive kidney disease. In many instances, these cases are likely diagnosed as glomerulonephritis with dominant C3 due to the absence of immunoglobulin staining by routine immunofluorescence microscopy. The patient reported here showed lymphomatous infiltration on kidney biopsy and mesangial proliferative glomerulonephritis with dominant staining for C3 without immunoglobulins on initial immunofluorescence; however, monotypic immunoglobulin G κ light chain was revealed after additional immunofluorescence staining was performed on the paraffin-embedded tissue. This patient's case highlights the evolving state of kidney biopsy interpretation and the expanding spectrum of kidney disease in the setting of hematopoietic neoplasia.

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