Marked hyperphosphatasemia associated with an acute leukemia in a Great Dane

This is the report of a 5‐year‐old male neutered Great Dane with an extreme leukocytosis (544.9 × 10⁹ cells/L; RI 5.2–13.9 × 10⁹ cells/L) characterized by highly atypical round cells. Cellular morphologic features such as cytoplasmic membrane blebs, a high nuclear‐to‐cytoplasmic ratio, and nuclear indentations and irregularities and large nucleoli, as well as immunocytochemistry for CD3 and CD79, myeloperoxidase cytochemistry, and clonality testing were not conclusive for myeloid or lymphoid origin. Marked alkaline hyperphosphatasemia was present at the first visit (2783.0 U/L; RI 6–80.0 U/L), followed by a 5‐fold increase (14,000 U/L) a week later, identified as being mostly contributed by the bone‐ALP isoform (11,062 U/L; RI 0–30 U/L). In addition, the atypical leukocytes were strongly positive for cytoplasmic ALP activity. In vitro lysis of a heparin blood sample resulted in a 1.7‐fold increase of ALP activity, supporting the origin of the hyperphosphatasemia at least in part from the leukemic cell population. To the authors’ knowledge, this is a unique case of alkaline hyperphosphatasemia, due at least to a leukemic cell population producing a bone‐ALP isoform, regardless of the exact nature of the leukemia.     

Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus‐negative cat

A 10‐year‐old castrated Domestic Short‐Haired cat was presented to a primary care veterinarian for a wellness examination and laboratory examination for monitoring of diabetes mellitus. The CBC revealed marked thrombocytosis, leukopenia and macrocytic, normochromic anemia. The cat tested negative for FeLV and feline immunodeficiency virus, but was positive for Mycoplasma haemominutum by PCR. Hematologic abnormalities were not responsive to therapy, so a repeat CBC and a bone marrow aspiration for cytology were performed. Additional blood smear findings included anisocytosis with megaloblastic erythroid precursors, large platelets, eosinophilic myelocytes and metamyelocytes, and rare unidentified blasts. The bone marrow smear was highly cellular, and the cytologic pattern was consistent with myelodysplastic syndrome with an erythroid predominance. At that time, 15% blasts were present. The cat was treated with a vitamin K₂ analog, doxycycline, and prednisolone, but without a clinical response. Within 3 months, euthanasia was elected due to declining quality of life, and a necropsy was performed. Postmortem bone marrow smears were highly cellular and dominated by monomorphic blasts of unknown line of origin (52%), persistent marked erythroid and megakaryocytic dysplasia, and ineffective erythropoiesis and granulopoiesis. Immunohistochemical, immunocytochemical, and cytochemical stains resulted in a diagnosis of acute myeloid leukemia of unclassified type. Additional histologic findings included mixed hepatitis with trematode infestation and lymphoplasmacytic interstitial nephritis with fibrosis. The marked thrombocytosis with myelodysplastic syndrome and the FeLV‐negative status of this cat were unusual. The difficulty in classifying the myelodysplasia and subsequent leukemia highlights a need for further reporting and characterization of these types of disease.     

Classification of myeloid neoplasms: a comparative review

Classification of myeloid neoplasms in veterinary medicine was modeled in the early 1990s after French-American-British and National Cancer Institute systems used in human medicine. Recently our physician counterparts, in collaboration with oncologists, constructed a new World Health Organization (WHO) standard. WHO revisions lower the blast threshold from 30% to 20% for diagnosing acute myeloid leukemia (AML) and expand and redefine AML categories. AML is now subdivided into 4 broad groups: 1) AML with recurrent genetic abnormalities, 2) AML with multilineage dysplasia, 3) AML with previous chemotherapy and/or radiation, and 4) AML, not otherwise categorized. AML alphanumeric designations (M1, M2, etc) have been discontinued as numbers of subtypes have increased. The lower blast percentage eliminates one category of myelodysplastic syndrome (MDS): refractory anemia with excess blasts in transformation. A new MDS category was created: refractory cytopenia with multilineage dysplasia (RCMD), with lineage dysplasia assessed using newly defined percentage limits. At least 10% of cells from each of 2 lineages must display atypia for a diagnosis of RCMD. That threshold is 50% for diagnosing AML with multilineage dysplasia. Chronic myelomonocytic leukemia has been removed from the MDS category and included in a new category of diseases that have features of both MDS and chronic leukemia. WHO revisions are a signal to veterinary clinical pathologists to assess the validity of our system, which was built on premises now questioned.     

Multilobulated "flower" cells in a subcutaneous mass aspirate from a cat

An 8-year-old intact male cat was presented with a subcutaneous mass in the region of the right jugular vein. Cytologic and histopathologic examinations revealed cells with multilobulated nuclei (flower cells). Immunochemistry using a panel of markers showed vimentin-positivity on cytologic specimens, and postive staining for CD79a and BLA36 on histologic specimens. The final diagnosis was lymphoma of B-cell origin. We have observed similar multilobulated cells in ascites fluid, thoracic fluid, and peripheral blood from dogs and cats with a variety of lymphoid and myeloid neoplasms. Cells with multilobulated nuclei that resemble flower petals also have been described in humans. These cells are infrequently observed in canine and feline cytology specimens and require immunochemistry to determine their cell of origin.     

BCR-ABL translocation in a dog with chronic monocytic leukemia

A 9-year-old female spayed mixed breed dog was evaluated at the University of Florida Small Animal Hospital for marked leukocytosis with no associated clinical signs. CBC abnormalities included marked leukocytosis (106,000/μL), marked monocytosis (78,000/μL), and the presence of 13% blast cells (13,832/μL), supporting a diagnosis of leukemia. Cytopenias and dysplastic changes in other cell lines were not present. Microscopic examination of bone marrow showed hypercellular uniparticles with a marginal increase in frequency of unclassified blast cells (2%), but was otherwise unremarkable. Flow cytometric immunophenotyping of blood cells determined that leukemic cells were CD45(+) , CD14(+) , and CD34(-) , and based on side scatter and CD45 reactivity the marrow contained 19% monoblasts. By immunocytochemical staining, the leukemic cells in the bone marrow were CD11b(+) , CD11c(+) , CD11d(+) , MHC-II(+) , MPO(+) , and CD34(-) . Fluorescence in situ hybridization (FISH) analysis of peripheral blood leukocytes documented a chromosomal translocation producing a BCR-ABL gene hybrid, similar to the "Philadelphia" chromosome abnormality recognized in human chronic myelogenous leukemia, as well as a phosphatase and tensin homolog (PTEN) gene deletion. Hydroxyurea therapy was attempted, but was ineffective; the dog died 7 months after initial presentation. Clinical and laboratory findings and the protracted course supported a diagnosis of chronic monocytic leukemia (CMoL) and, to our knowledge, this is the first case of CMoL with a BCR-ABL chromosomal abnormalitiy described in dogs. This may have clinical implications for treatment of dogs with chronic leukemias associated with particular genetic mutations. However, more case studies are needed to further characterize this disease.     

Myeloproliferative disease with megakaryocytic predominance in a dog with occult dirofilariasis

A 7-year-old male German Shepherd dog with a history of lethargy, weight loss and severe anemia was referred to the University of Florida Veterinary Medical Teaching Hospital for examination. Abnormal laboratory findings included a normocytic and normochromic anemia, thrombocytosis, eosinophilia, basophilia and hyperproteinemia. An increased pulmonary density in the caudal lung lobes was observed on thoracic radiographs. Bone marrow aspiration and core biopsy revealed a hypercellular bone marrow with increased numbers of unidentified blast cells and bizarre megakaryocyte proliferation. Circulating microfilariae were not present in the blood, but serum examined by immunofluorescence was strongly positive for antibodies against Dirofilaria immitis microfilariae. A diagnosis of myeloproliferative disease with megakaryocytic predominance and occult dirofilariasis was made.