RAS, FLT3, and C-KIT mutations in immunophenotyped canine leukemias.

OBJECTIVE: To determine the frequency of FLT3, C-KIT, and RAS mutations in canine leukemia patients. MATERIALS AND METHODS: Ethylenediamine tetra-acetic acid blood samples were recruited from dogs with suspected leukemia, categorized by quantitative and cytological evaluation and immunophenotyping. Flow cytometry was carried out using antibodies against CD3; CD3e; CD4; CD5; CD8; CD11a, b, c, and d; CD14; CD21; CD34; CD45 and 45RA; CD79a; CD90 (THY-1); major histocompatibility complex II; myeloperoxidase; MAC387; and neutrophil-specific antibody. Genomic DNA was extracted from whole blood and analyzed for mutations in N, H, and K-RAS, FLT3, and C-KIT genes by polymerase chain reaction and sequencing. RESULTS: Fifty-seven (77.0%) of 74 samples submitted from dogs with suspected leukemia had cytologically and immunophenotypically confirmed leukemia. There were 36 (63.2%) acute leukemias, 16 (28.1%) chronic, 3 (5.3%) prolymphocytic, 1 natural killer cell, and 1 chronic leukemia undergoing blast transformation. N-RAS mis-sense mutations were identified in 14 (25%) dogs with acute myeloid (AML) or lymphoid (ALL) leukemia, and also in one dog in the leukemic phase of lymphoma. Mutations in K-RAS were found in two dogs with AML. There were no H-RAS mutations. FLT3 internal tandem duplications were identified in three dogs with ALL, and a mis-sense mutation was found in one dog with ALL. C-KIT mutations were identified in three dogs with AML. Sixty-one percent of dogs with acute leukemia harbored mutations in N/K-RAS, FLT3, or C-KIT. CONCLUSION: RAS, FLT3, and C-KIT mutations, analogous to those found in human leukemia, occur commonly in acute canine leukemia.

Solitary plasmacytoma of bone in two successfully treated cats.

This is the first report of feline solitary plasmacytoma of bone. We describe the clinical, clinico-pathological, radiographic and pathological findings of two successfully treated cats with long-term follow-up. The first case presented with spinal pain and neurological deficits. Radiographs demonstrated sclerosis of lumbar vertebra L6 and a myelogram confirmed interference to flow of contrast in the L4-7 region. A biopsy of L6 revealed neoplastic plasma cell infiltration. There was no evidence of paraproteinaemia on serum protein electrophoresis. The cat underwent hypofractionated megavoltage radiotherapy. Clinical signs resolved completely and 4 years after diagnosis the cat remains well and has no electrophoretically detectable paraproteinaemia. The second case presented with neurological deficits of the tail and spinal radiographs revealed extensive osteolysis of the sacrum. A biopsy of sacral bone demonstrated neoplastic plasma cell infiltration. The animal was normoglobulinaemic. The cat improved clinically with induction chemotherapy (melphalan and methylprednisolone). The same chemotherapeutics were continued at maintenance doses for 4.3 years, at which time there was recurrence of neurological deficits and a palpable sacral mass. Cytological examination of a fine needle aspirate confirmed recurrence of plasma cell neoplasia. A low concentration monoclonal paraproteinaemia was detected. Vincristine was administered resulting in resolution of neurological deficits and a palpably smaller sacral mass. Eighteen months into vincristine therapy, there was recurrence of clinical signs and the cat was euthanased, more than 6 years after the initial diagnosis.

Myeloma-related disorders in cats commonly present as extramedullary neoplasms in contrast to myeloma in human patients: 24 cases with clinical follow-up.

BACKGROUND: Myeloma-related disorders (MRD) are rare neoplasms of plasma cells. Published case reports describe a diversity of clinical presentations with confusing terminology and diagnostic criteria as a consequence of the assumption that MRD in cats are analogous to those in dogs or humans. OBJECTIVE: The aim of the study was to describe clinical, clinicopathologic and imaging findings, response to treatment, survival and possible associations with other diseases or vaccination in a large case series. A priori hypotheses were that cats with MRD commonly present with extramedullary involvement and uncommonly have radiographic bone lesions, in contrast to human patients. ANIMALS: Twenty-four cats with MRD confirmed by cytology or histopathology and immunohistochemistry. METHOD: A multicenter retrospective study was performed. RESULTS: Two types of clinical presentation were observed. The first group (n = 17) had neoplasia involving abdominal organs, bone marrow, or both. All developed systemic clinical signs and paraproteinemia. Five of 7 cats that received chemotherapy improved clinically or had decreased serum globulin concentration (median survival, 12.3 months; range, 8.5-22 months). The second group comprised 7 cats with skin masses, 2 of which were paraproteinemic and developed rapidly worsening systemic signs. In cats without systemic signs, excision of the skin masses appeared to be associated with prolonged survival (up to 2.4 years). Cats with MRD commonly presented with extramedullary involvement (67%), versus humans with MRD (5%) (P < .001), and uncommonly presented with radiographic bone lesions (8%) versus humans with MRD (80%) (P < .001). CONCLUSIONS: Radiographic bone lesions are uncommon in cats with MRD and extramedullary presentation is common, relative to human myeloma.

High serum troponin I concentration as a marker of severe myocardial damage in a case of suspected exertional heatstroke in a dog.

A young, overweight dog presented with sudden onset lethargy and collapse following exercise in warm environmental conditions. Investigations revealed systolic hypotension, multiform ventricular premature complexes, irregular myocardial echogenicity with poor left ventricular systolic function and a markedly elevated troponin cTnI (180ng/mL, reference range <0.3ng/mL) consistent with severe myocyte damage. Infectious causes of myocarditis were ruled out on the basis of serological and polymerase chain reaction blood tests. Exercise-induced malignant hyperthermia was excluded from the history, an exercise tolerance test and genetic testing for the RYR1 V547A mutation. The diagnosis was myocardial damage secondary to suspected exertional heatstroke, from which the dog recovered uneventfully over a number of weeks and serum troponin normalised. This is the first case report in any species including man, documenting high troponin as a marker of severe myocardial damage following suspected heatstroke.