Paraneoplastic thrombocytosis-induced systemic thromboembolism in a cat

A six-year-old cat presented with clinical signs consistent with distal aortic thromboembolism while clinical signs of cardiovascular disease were absent. Diagnostics, including thoracic radiographs, electrocardiography, and echocardiography revealed no cardiovascular anomalies. Thoracic radiographs revealed multifocal pulmonary lesions consistent with neoplasia. Complete blood cell count demonstrated a marked thrombocytosis, leukopenia, and neutropenia. Histopathology of the pulmonary lesions confirmed multiple bronchoalveolar carcinomas. Myelodysplasia with megakaryocytic hyperplasia and ineffective myelopoiesis was noted on bone-marrow histopathology from multiple sites. The absence of other causes suggested a paraneoplastic thrombocytosis. The diagnosis of paraneoplastic thrombocytosis-induced thromboembolism was made due to the lack of underlying cardiac disease and the presence of a marked thrombocytosis. The presence of thrombocytosis and thromboembolism associated with neoplasia is discussed.     

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.     

Probable Essential Thrombocythemia in a Dog

Essential thrombocythemia (ET) in an 11-year-old dog was characterized by persistently high platelet counts (range, 4.19 X 10(6)/microliters to 4.95 X 10(6)/microliters, abnormal platelet morphology, marked megakaryocytic hyperplasia in the bone marrow, absence of circulating megakaryoblasts, and history of splenomegaly and gastrointestinal bleeding. Increased numbers of megakaryocytes and megakaryoblasts (15% to 20%) in the bone marrow were confirmed by a positive acetylcholinesterase reaction. Another significant finding was the presence of a basophilia in blood (4,836/microliters) and bone marrow. The marked persistent thrombocytosis, absence of reactive (secondary) thrombocytosis, abnormal platelet morphology, and quantitative and qualitative changes in the megakaryocytic series in the bone marrow suggested the presence of a myeloproliferative disease. Cytochemical and ultrastructural findings aided in the diagnosis of ET. The dog was treated with radiophosphorus. The results was a rapid decline in the numbers of megakaryoblasts and megakaryocytes in the bone marrow and platelets and basophils in the peripheral blood. The dog died unexpectedly of acute necrotizing pancreatitis and diabetes mellitus before a complete remission was achieved.     

Acute monocytic leukemia in an irradiated Beagle.

A purebred female Beagle dog that had received 2,000 R of protracted wholebody gamma-irradiation from 60Co when 14 months old had hematologic changes consistent with a myeloproliferative disorder 3 years after the termination of radiation exposure. Peripheral blood and bone marrow findings during the 7-month period before death showed progressive anemia with increased numbers of platelets; immature granulocytes, monocytes and promonocytes. A period of partial remission occurred during which time the peripheral blood was aleukemic, although there was marked thrombocytosis and abnormal erythropoiesis which was evidenced by bizarre circulating nucleated red cells, anisocytosis, poikilocytosis and Howell-Jolly bodies. The dog had a terminal crisis with marked leukocytosis, most cells in the peripheral blood being bizarre monocytes and promonocytes. Tissues obtained at necropsy showed diffuse as well as focal infiltration of the spleen, liver, lymph nodes, heart, kidney and gastrointestinal wall with immature neoplastic cells resembling monocytes and monocytic precursors. The monocytic differentiation of the invasive cell population was confirmed by morphological, cytochemical, histological, ultrastructural and in vitro cell culture studies.     

Thrombocytosis in 24 Horses (1989–1994)

The records of horses presented to the Veterinary Teaching Hospital of North Carolina State University College of Veterinary Medicine between January 1, 1989 and April 30, 1994 were evaluated to determine risk factors associated with thrombocytosis. Of the 2,346 horses for which a CBC was performed, 24 (1.0%) had a platelet count > 400,000/μL. Demographic, diagnostic, physical examination, and clinicopathologic variables from these cases were compared with a reference population consisting of 189 horses with a normal platelet count presenting during the same period. Infectious/inflammatory disorders were observed more commonly in horses with high platelet counts than in horses with normal platelet counts. Initial independent evaluation of demographic variables revealed that horses more than 3 years of age, females, and geldings were less likely to have thrombocytosis than were younger horses or stallions. Independent analysis of clinicopathologic variables revealed that horses with thrombocytosis were more likely to have hyper-fibrinogenemia, leukocytosis, hypoproteinemia, and anemia than were horses with normal platelet counts. Physical examination parameters associated with thrombocytosis included tachycardia and pyrexia. In the final multivariable model, the variables with the strongest association with thrombocytosis included leukocytosis, anemia, and hyper-fibrinogenemia. Thrombocytosis rarely causes clinical problems in horses and is not likely to require specific antiplatelet therapy. The strong association of thrombocytosis with infectious/inflammatory disorders, however, should lead clinicians to suspect these types of conditions in horses with high platelet counts.     

Thrombocytosis in cats: a retrospective study of 51 cases (2000-2005)

Feline haematology profiles of patients presented to the University of Bristol Small Animal Hospital from January 2000 to October 2005 were evaluated for thrombocytosis (defined as a platelets count of >700x10(9)/l and confirmed on smear evaluation). Thrombocytosis was found in 79 cats (4.64% of the hospital feline population), with values ranging from 703 to 1895x10(9)/l. Signalment, clinical presentation, concurrence of other haematological abnormalities, diagnoses and outcome were evaluated in 51 cases in which complete medical records were available. Other variables (feline immunodeficiency virus/feline leukaemia virus status, thyroxine level, haemoplasma PCR, toxoplasma antibody titres) were also evaluated. No association was found between the presence of thrombocytosis and breed or gender. Gastrointestinal signs were the most common clinical presentation. Lymphopenia was the most common concurrent haematological abnormality. Based on final diagnosis reached, cats were grouped both according to the DAMNITV classification and according to the body system affected. Amongst the DAMNITV classification, inflammatory/infectious conditions were most commonly associated with thrombocytosis. According to body systems, gastrointestinal involvement was most represented, followed by endocrine cases. No association was found between the severity of thrombocytosis and outcome.     

Thrombocytosis associated with a myeloproliferative disorder in a dog

A dog with a myeloproliferative disorder and thrombocytosis had clinical signs that were consistent with a diagnosis of essential thrombocythemia. The dog was treated with aspirin, radioactive phosphorus, and melphalan. Eighteen months after referral, the disorder progressed to chronic granulocytic leukemia, and treatment was switched to hydroxyurea. Fourteen months later, the dog was euthanatized because of uncontrollable atrial fibrillation.     

Thrombocytosis and central nervous system involvement in a case of canine acute megakaryoblastic leukemia

This case report presents a 14‐month‐old female Poodle mix with acute megakaryoblastic leukemia based on a marked thrombocytosis, abnormal platelet morphology, circulating dwarf megakaryocytes, and blast cells in the blood. Bone marrow abnormalities included dysmegakaryopoiesis dygranulopoiesis, and an increased number of blast cells was observed in the blood. Extensive leukemic involvement was also found in the liver, spleen, lymph nodes, lungs, kidneys, and brain. The cytopathologic features of the abnormal circulating cells were highly suggestive of being megakaryocytic in origin, which was supported by negative myeloperoxidase staining and positive von Willebrand factor staining on immunocytochemistry (ICC). The neoplastic cells were also CD61 positive and had variable von Willebrand factor expression on ICC. Although there were only 25% blast cells in the bone marrow, which theoretically supported myelodysplastic syndrome, the hypothesis that this case represented acute myeloid leukemia of megakaryoblastic origin was confirmed by the continuous increase in circulating blast cell numbers during follow‐up visits and the extensive leukemic involvement of parenchymal organs.     

Factitious Hyperkalemia in Dogs With Thrombocytosis

To determine the effect of platelet count on the accurate assessment of serum electrolyte concentrations, simultaneous platelet counts and electrolyte determinations were performed on serum and plasma from 40 dogs. Dogs were grouped according to platelet count as follows: thrombocytopenic (less than 150,000/microliters), normal (150,000 to 600,000/microliters), or thrombocytotic (greater than 600,000/microliters). Serum potassium concentration was significantly higher than plasma potassium concentration in normal dogs (mean difference, 0.63 +/- 0.17 mEq/l) and in dogs with thrombocytosis (mean difference, 1.55 +/- 0.73 mEq/l). This difference in potassium concentration between serum and plasma was positively correlated with platelet count (r2 = 0.86). In the blood of dogs with thrombocytosis, the serum-plasma potassium difference was further increased when the time period between blood collection and separation of serum or plasma from cells was lengthened. Differences between serum and plasma concentrations of sodium or chloride were not seen in any platelet group. These results suggest that a portion of the measured serum potassium concentration is released from platelets during the clotting process. In fact, profound elevations in serum potassium concentrations can occur factitiously in dogs with thrombocytosis. Therefore, the actual concentration of potassium in blood is determined more accurately by measuring the plasma concentration rather than the serum concentration of this electrolyte.     

A dog with acute myelomonocytic leukemia

A three-year-old dog with marked leukocytosis, lymphadenopathy, and diarrhea showed an increase in unidentified blasts in the peripheral blood, and they were proliferated in the bone marrow. The dog was diagnosed with myelomonocytic leukemia (M4) because the blast cells were demonstrated by cytochemical staining to be both myeloid and monocytic cells. Although the dog was treated with a multi-combination chemotherapy and induction therapy using vitamin K2, it died on day 47 after the first admission. This case is the first report of M4 in Japan.     

Central nervous system lymphosarcoma in the dog

Central nervous system lymphosarcoma was diagnosed in 8 dogs with seizures and clinical signs compatible with multifocal central nervous system involvement. Cerebrospinal fluid analysis showed high white cell counts with abnormal lymphoid cells in all dogs, and high protein concentration in 5 dogs. Two dogs were given systemic anticancer chemotherapy, and 4 dogs were given a combination of systemic chemotherapy, intrathecal cytosine arabinoside, and craniospinal irradiation, resulting in marked improvement of the clinical signs.     

Acute myelomonocytic leukemia (AML-M4) in a dog with the extradural lesion

A two-year-old dog having presented with neurological signs showed marked leukocytosis and appearance of blast cells in the peripheral blood. Hematological and bone marrow examination showed an increase in blasts having both myeloid and monocytic cells characteristics. The dog was diagnosed with acute myelomonocytic leukemia (AML-M4) on the basis of bone marrow findings. Although the dog was treated with a multi-combination chemotherapy, the neurological abnormalities progressed and the dog was euthanized. Myelographic examination and necropsy revealed the extradural lesion formed by AML-M4 around the cervical spinal cord and this lesion was considered as a cause of the neurological signs.     

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.     

Correlation of spurious potassium elevation and platelet count in dogs

Paired serum and plasma electrolyte determinations were measured on 26 dogs. The difference between plasma and serum electrolyte concentrations was compared to the platelet and leukocyte counts. An increase in serum potassium concentration over plasma potassium concentration was found which correlated linearly with the platelet count. No correlation with white cell count was found. A statistically significant increase in serum sodium concentration over plasma sodium concentration was also noted, however, this change did not correlate with the number of platelets or white cells. It is concluded that thrombocytosis, previously known to cause spurious elevation in serum potassium concentration in humans, can also do so in dogs and, presumably, other species.     

Acute lymphoblastic leukemia in a juvenile southern black rhinoceros (Diceros bicornis minor).

A 21-mo-old female southern black rhinoceros (Diceros bicornis minor) developed acute upper respiratory dyspnea in association with lymphadenopathy and marked immature lymphocytosis. A diagnosis of acute lymphoblastic leukemia was reached on the basis of the morphologic and cytochemical characteristics of peripheral lymphoblasts. Antineoplastic chemotherapy included administration of cytarabine, cyclophosphamide, vincristine, and doxorubicin, with clinical remission achieved 19 days after initiation of treatment. The rhinoceros died, however, of congestive heart failure, presumably secondary to doxorubicin cardiotoxicity and a particular sensitivity of rhinoceros myocardial tissue to free hydroxyl radicals. The pharmacologic effects of any therapeutic agent need to be carefully considered before use in the black rhinoceros, especially within the context of the unique physiology of this species.     

Mucinous cholangiocarcinoma in a cat

Mucinous cholangiocarcinoma was diagnosed in a 14-year-old, castrated male, domestic shorthaired cat with marked peritoneal effusion. Cytological confirmation of malignancy by fluid analysis and fine-needle, ultrasound-guided aspiration of the liver was followed by histological examination of tissue samples obtained at surgery and necropsy. No observed response followed chemotherapy with doxorubicin and carboplatin. Electron microscopy and immunohistochemistry helped to further characterize this unusual tumor.     

Hypereosinophilic syndrome in two cats

Two cats showing chronic vomiting, diarrhea and weight loss were found to have leukocytosis with marked eosinophilia. Both cats were diagnosed with hypereosinophilic syndrome by the findings of increased eosinophils and their precursors in the bone marrow, eosinophilic infiltration into multiple organs, and exclusion of other causes for eosinophilia. Although cytoreductive chemotherapy with hydroxycarbamide and prednisolone was performed, these two cats died 48 days and 91 days after the initial presentation.     

Long-term survival after combination chemotherapy for bilateral renal malignant lymphoma in a dog

CASE HISTORY: A 6-year-old, entire male Flat-coated Retriever was presented with a history of lethargy, polydipsia and seizures. Clinical chemistry had shown marked azotaemia. CLINICAL FINDINGS AND DIAGNOSIS: Radiography and ultrasonography revealed bilateral renomegaly, and cytology of fine needle aspirates from the kidneys was diagnostic of malignant lymphoma. The dog was treated with a modified high-dose cyclophosphamide-, vincristine-, and prednisolone-based chemotherapy protocol, achieved remission, and returned to normal quality of life. Survival time was 346 days from the time of diagnosis. CLINICAL RELEVANCE: Malignant lymphoma in the kidneys of dogs has been considered to carry a uniformly poor prognosis. Long-term remission after medical treatment has not previously been reported. The favourable outcome in this case illustrates the limitations of clinical staging in determining the outcome for individual patients.     

Acute tumour lysis syndrome in a dog with B-Cell multicentric lymphoma

A 5-year-old, spayed female German Shepherd dog was admitted to hospital with marked generalised lymphadenomegaly and splenomegaly. A stage Va B-cell multicentric lymphoma was diagnosed on clinical, cytological (lymph node, bone marrow), histological-immunohistochemical (lymph node excision) and imaging grounds. Since no satisfactory remission was achieved using a multi-drug chemotherapy protocol that included cyclophosphamide, vincristine, cytosine arabinoside, prednisolone, and subsequently supplemented by L-asparaginase, it was replaced by another protocol combining vincristine, L-asparaginase, prednisolone, cyclophosphamide and doxorubicin. Soon after the third weekly session of the second protocol, the clinical status of the animal deteriorated suddenly and severely, with a bleeding tendency, jaundice, hyperuricaemia, hyperphosphataemia, azotaemia, hyperbilirubinaemia and, presumptive disseminated intravascular coagulation. There was also complete regression of lymphadenomegaly. This report emphasises the clinicopathological features and the diagnostic peculiarities of the acute tumour lysis syndrome, which occurs uncommonly in dogs.     

Ectopic cervical thymic carcinoma in a dog

A 10-year-old male German shepherd dog was referred for evaluation of a cranial cervical mass causing progressively worsening respiratory distress. A fine-needle aspirate of the mass was obtained and the cytology results were compatible with a carcinoma. The dog underwent chemotherapy without clinical improvement and was ultimately euthanased because of clinical deterioration. At post-mortem examination, an irregular multi-lobated mass in the cranial cervical region was observed causing ventro-lateral tracheal deviation. Histopathology and immunohistochemistry revealed a mixed population of CD3 lymphocytes and macrophages in an exuberant fibrous stroma, associated with dispersed cytokeratin-positive epithelial cells with marked eosinophilic cytoplasm. Some of the epithelial cells were arranged in concentric clusters that were interpreted as Hassall's corpuscles. Histopathological examination of the thyroid gland revealed several neoplastic emboli composed of epithelial cells similar to those observed in the cervical mass. To the authors' knowledge, this is the first report of an ectopic cervical thymic carcinoma in a dog.