Myelodysplasia: differentiating neoplastic from nonneoplastic syndromes of ineffective hematopoiesis in dogs.

In the context of human hematopathology, the terms myelodysplasia and Myelodysplastic Syndromes (MDS) are applied to disorders of hematopoiesis that are clonal, neoplastic, and, in most forms, manifested as ineffective hematopoiesis with characteristic morphologic abnormalities in multiple cell lines. Studies of human patients have provided the conceptual framework that MDS evolve from a multipotential hematopoietic stem cell (CFU-GEMM) that has undergone neoplastic transformation as the result of acquired genetic mutations. The diagnosis of MDS in human patients is based largely on morphologic examination of marrow but can be confirmed by detection of cytogenetic abnormalities. Spontaneous, neoplastic myelodysplasia occurs in dogs, but rarely. Nonneoplastic syndromes of ineffective hematopoiesis are more common in dogs, can resemble MDS, and are probably immune mediated in many cases. Drugs and their metabolites are potential causes of dysmorphic maturation and ineffective hematopoiesis. Without methods to confirm clonality by cytogenetic analysis, the diagnosis of neoplastic myelodysplasia in dogs is based onlight microscopic examination of bone marrow smears. This paper discusses and illustrates the characteristic morphologic and cytochemical features of neoplastic myelodysplasia and nonneoplastic ineffective hematopoiesis in dogs.

Diagnosis of chronic myelogenous leukemia in a dog using morphologic, cytochemical, and flow cytometric techniques.

Chronic myelogenous leukemia was diagnosed in a 3.5-year-old neutered male Golden Retriever. The diagnosis was based on persistent leukocytosis (>73.0X10(3)/microliter), composed of a proportionate left shift to progranulocytes with no evidence of underlying inflammation, infection, or neoplasia. Marked dysplasia was evident in neutrophils and platelets in peripheral blood. Bone marrow and splenic aspirates were dominated by mature and immature neutrophils with < 2% myeloblasts. Cytochemical and flow cytometric assays confirmed that cells in the peripheral blood and spleen were of committed neutrophil lineage. The dog responded initially to treatment with hydroxyurea, but developed acute undifferentiated leukemia approximately 83 days after initial presentation.

Proposed criteria for classification of acute myeloid leukemia in dogs and cats.

Blood and bone marrow smears from 49 dogs and cats, believed to have myeloproliferative disorders (MPD), were examined by a panel of 10 clinical pathologists to develop proposals for classification of acute myeloid leukemia (AML) in these species. French-American-British (FAB) group and National Cancer Institute (NCI) workshop definitions and criteria developed for classification of AML in humans were adapted. Major modifications entailed revision of definitions of blast cells as applied to the dog and cat, broadening the scope of leukemia classification, and making provisions for differentiating erythremic myelosis and undifferentiated MPD. A consensus cytomorphologic diagnosis was reached in 39 (79.6%) cases comprising 26 of AML, 10 of myelodysplastic syndrome (MDS), and 3 of acute lymphoblastic leukemia (ALL). Diagnostic concordance for these diseases varied from 60 to 81% (mean 73.3 +/- 7.1%) and interobserver agreement ranged from 51.3 to 84.6% (mean 73.1 +/- 9.3%). Various subtypes of AML identified included Ml, M2, M4, M5a, M5b, and M6. Acute undifferentiated leukemia (AUL) was recognized as a specific entity. M3 was not encountered, but this subclass was retained as a diagnostic possibility. The designations M6Er and MDS-Er were introduced where the suffix "Er" indicated preponderance of erythroid component. Chief hematologic abnormalities included circulating blast cells in 98% of the cases, with 36.7% cases having >30% blast cells, and thrombocytopenia and anemia in approximately 86 to 88% of the cases. Bone marrow examination revealed panmyeloid dysplastic changes, particularly variable numbers of megaloblastoid rubriblasts and rubricytes in all AML subtypes and increased numbers of eosinophils in MDS. Cytochemical patterns of neutrophilic markers were evident in most cases of Ml and M2, while monocytic markers were primarily seen in M5a and M5b cases. It is proposed that well-prepared, Romanowsky-stained blood and bone marrow smears should be examined to determine blast cell types and percentages for cytomorphologic diagnosis of AML. Carefully selected areas of stained films presenting adequate cellular details should be used to count a minimum of 200 cells. In cases with borderline diagnosis, at least 500 cells should be counted. The identity of blast cells should be ascertained using appropriate cytochemical markers of neutrophilic, monocytic, and megakaryocytic differentiation. A blast cell count of > 30% in blood and/or bone marrow indicates AML or AUL, while a count of < 30% blasts in bone marrow suggests MDS, chronic myeloid leukemias, or even a leukemoid reaction. Myeloblasts, monoblasts, and megakaryoblasts comprise the blast cell count. The FAB approach with additional criteria should be used to distinguish AUL and various subtypes of AML (Ml to M7 and M6Er) and to differentiate MDS, MDS-ER, chronic myeloid leukemias, and leukemoid reaction. Bone marrow core biopsy and electron microscopy may be required to confirm the specific diagnosis. Immunophenotyping with lineage specific antibodies is in its infancy in veterinary medicine. Development of this technique is encouraged to establish an undisputed identity of blast cells. Validity of the proposed criteria needs to be substantiated in large prospective and retrospective studies. Similarly, clinical relevance of cytomorphologic, cytochemical, and immunophenotypic characterizations of AML in dogs and cats remains to be determined.