Myeloproliferative disease in the dog and cat: definition, aetiology and classification

The term myeloproliferative disease may be applied to all the non-lymphoid dysplastic and neoplastic conditions arising from the haematopoietic stem cell or its progeny. Thus the chronic and acute myeloid leukaemias, thrombocythaemia, megakaryocytic myelosis, myelofibrosis, the myelodysplastic syndromes and some cases of aplastic anaemia may be viewed as variants of a single disease process. This view is useful in explaining the common occurrence of mixed forms of disease or interconversions between the myeloproliferative diseases. This variability is a consequence of the development of all the haematopoietic lineages from a single class of haematopoietic stem cell by progressive differentiation. The aetiology of the myeloproliferative diseases in the domestic animals is uncertain but feline leukaemia virus infection has been implicated in the cat. These conditions may be classified as aplastic anaemia, as preleukaemic dysplastic conditions with variable cytopenias and morphological abnormalities of blood cells, as smouldering leukaemias, or as leukaemias with a frankly leukaemic blood or bone marrow.     

Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders

Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia.     

Clinical aspects of feline immunodeficiency and feline leukemia virus infection

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries.     

Immune-mediated neutropenia suspected in five dogs

Five cases of suspected immune-mediated neutropenia in dogs are described. Clinical signs varied depending on whether the animals had a systemic infection or concurrent immune-mediated disease. Patients were diagnosed by excluding other causes of neutropenia, supportive bone marrow aspirate findings, an initial favourable response to corticosteroid administration in four of the cases, and concurrent immune-mediated disease. Four of the dogs were receiving medications at the time of diagnosis, and immune-mediated neutropenia secondary to drug therapy cannot be excluded. This study shows that appropriate immunosuppressive treatment can lead to a favourable outcome, however, care is required to avoid adverse effects associated with corticosteroid use. It is also imperative that medications are not withdrawn abruptly as a second remission may not always be achievable.     

Bone Marrow Cytological Findings in 4 Dogs and a Cat With Hemophagocytic Syndrome

Hemophagocytic syndrome or hemophagic histiocytosis was diagnosed in 4 dogs and 1 cat by evaluation of bone marrow aspirate smears. One of the dogs had a suspected infection with canine parvovirus and a confirmed infection with Salmonella spp, 2 dogs had presumptive diagnoses of myeloproliferative and lymphoproliferative disease, respectively, and 1 dog died without a diagnosis. The cat had hepatic lipidosis and lesions compatible with feline calicivirus infection. All animals had cytopenias involving 2 or more cell lines, and fragmented erythrocytes in the blood, along with mild to moderate increases in the number of macro-phages in the bone marrow. Numerous marrow macro-phages contained phagocytized hematopoietic cells. Other cytological features of the bone marrow were variable in each patient, but the degree of response in the blood was inadequate, even in those with bone marrow hyperplasia. The phagocytosis of hematopoietic elements did not appear to be caused by a primary immune disorder, but rather by the inappropriate activation of normal macrophages secondary to infectious, neoplastic, or metabolic diseases. These findings suggest that hemophagocytic syndrome may be an important factor in the development of cytopenias; the data also support the cytological evaluation of bone marrow aspirates as an aid in the diagnosis of hemophagocytic syndrome. J Vet Intern Med 1996;10:7–14. Copyright © 7996 by the American College of Veterinary Internal Medicine .     

A retrospective study of aplastic pancytopenia in the dog: 9 cases (1996-2003)

BACKGROUND: Aplastic pancytopenia is defined by the presence of pancytopenia in blood and a hypocellular bone marrow with the hematopoietic space replaced by adipose tissue. Several causes of acquired aplastic pancytopenia are known; however, in some cases, an underlying cause is never determined. OBJECTIVE: The objective of this retrospective study was to identify the incidence, potential causes, and outcome of aplastic pancytopenia in dogs. METHODS: Bone marrow cytologic and core biopsy reports were reviewed to identify dogs diagnosed with aplastic pancytopenia between July 1, 1996 and June 30, 2003. Four-hundred eighty-six bone marrow reports that included aspirate and core biopsy evaluations were reviewed. Signalment, treatment given, previous and current disease conditions, clinical signs of disease, clinical laboratory data, therapy, response to therapy, and survival time were recorded. RESULTS: Nine dogs (1.85% of bone marrow samples reviewed) met the criteria for inclusion. Two dogs (22%) had associated diseases that included monocytic ehrlichiosis and Sertoli cell tumor. In 7 dogs (78%), the cause of aplastic pancytopenia could not be definitively determined, although an idiosyncratic drug reaction to griseofulvin was suspected in 1 of the dogs. The median age of dogs diagnosed with aplastic pancytopenia was 3.2 years, and apparent breed or sex predilection was not identified. Median HCT, total WBC count, and platelet count on the day of presentation were 21.8%, 1.0 x 10(3)/microL, and 2.0 x 10(3)/microL, respectively. Six of 9 dogs diagnosed with aplastic pancytopenia died or were euthanized within 21 days. Two dogs had complete hematologic recovery. One dog was living 3 years after diagnosis, but hematologic recovery was never documented. CONCLUSIONS: Aplastic pancytopenia is diagnosed infrequently and idiopathic aplastic pancytopenia may account for up to 67% or more of canine cases. Although the prognosis is guarded, some dogs with aplastic pancytopenia recover.     

Canine rickettsial infections.

Dogs that live in tick-infested areas are at risk for contracting rickettsial infections. Clinical signs associated with ehrlichiosis or Rocky Mountain spotted fever may be dramatic or mild. Clinicians must consider the possibility of rickettsial diseases to request laboratory tests that will permit a proper diagnosis. Specific antimicrobial therapy usually brings about clinical improvement, although some dogs may not be cleared of rickettsial organisms, even with prolonged treatment. A small percentage of dogs die of rickettsial infections, either in the acute stage or owing to chronic bone marrow suppression and generalized debilitation. Ocular lesions are an important clinical sign in canine rickettsial infections and may aid the clinician in making a diagnosis and monitoring response to therapy.     

Histoplasmosis in dogs and cats

Histoplasma capsulatum is endemic throughout most of the United States with a high prevalence of infections in the Midwest and South. Histoplasmosis is the second most common systemic fungal disease in cats that may be more susceptible than dogs. Infection occurs by inhalation of conidia from the mycelial phase, which subsequently convert to the yeast form. Histoplasma capsulatum is phagocytized and harbored by cells of the mononuclear phagocyte system. Infection may be subclinical or cause clinical pulmonary granulomatous disease or dissemination. Disseminated disease predominantly affects the liver, spleen, gastrointestinal tract, bone and bone marrow, integument, and eyes. Primary gastrointestinal histoplasmosis also occurs. Clinical signs of histoplasmosis often are nonspecific, including chronic wasting, fever, anorexia, respiratory signs, and lameness. Gastrointestinal signs (eg, diarrhea with hematochezia or melena) are common in dogs. The definitive diagnosis is made by identification of the yeast in tissue samples. Itraconazole is the treatment of choice.     

Bone marrow necrosis in dogs: 34 cases (1996-2004)

OBJECTIVE: To identify the incidence, potential causes, and clinical and clinicopathologic features of bone marrow necrosis in dogs. DESIGN: Retrospective study. ANIMALS: 34 client-owned dogs. PROCEDURES: Reports of cytologic examinations of bone marrow specimens performed between 1996 and 2004 were reviewed. All reports that indicated the presence of necrosis, stromal disruption, phagocytic macrophages, individual cell necrosis, or myelofibrosis were evaluated further. RESULTS: Of 609 reports of bone marrow evaluations performed during the study period, 34 (5.6%) had evidence of bone marrow necrosis. Nine dogs had no evidence of associated diseases or drug or toxin exposure, and 25 dogs had associated disease conditions or drug exposures. All 9 dogs with idiopathic bone marrow necrosis were anemic (mean Hct, 14%), but only 3 had neutropenia, and 3 had thrombocytopenia. All 9 had myelofibrosis. Of the 25 dogs with associated disease conditions or drug exposures, only 14 (56%) had anemia (mean Hct, 33%). In addition, 14 (56%) had neutropenia and 18 (72%) had thrombocytopenia. Only 10 (40%) had myelofibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that bone marrow necrosis may be common in dogs with hematologic disorders. In most dogs, bone marrow necrosis was associated with an underlying disease condition or drug exposure, but idiopathic bone marrow necrosis was also identified. Disease conditions that should increase suspicion of possible bone marrow necrosis include sepsis, lymphosarcoma, and systemic lupus erythematosus; drug exposures that should increase suspicion of possible bone marrow necrosis include chemotherapeutic agents, phenobarbital, carprofen, metronidazole, and mitotane.     

Differentiating benign and malignant causes of lymphocytosis in feline bone marrow

Differentiation of benign and malignant causes of lymphocytosis in blood or bone marrow can be problematic. In the present study, reports of examinations of bone marrow from cats, submitted over an 8-year period, were reviewed to identify cats with increased numbers of small lymphocytes. Of 203 reports reviewed, 12 (5.9%) indicated increased numbers of small lymphocytes. Diagnoses for these cats included chronic lymphocytic leukemia (CLL; n = 2), pure red cell aplasia (PRCA; n = 4), immune-mediated hemolytic anemia (IMHA; n = 3), thymoma (n = 1), cholangiohepatitis (n = 1), and fever of unknown origin (n = 1). Several factors were identified that could be used to differentiate reactive lymphocytosis from CLL. Cats with CLL tended to be older, and lymphocytes were slightly larger and had cleaved or lobulated nuclei. Reactive lymphocytosis was associated with immune-mediated anemias and inflammatory diseases. In reactive lymphocytosis, the proliferating lymphocytes were organized into lymphoid aggregates in bone marrow and were predominately B cells. Alternatively, in CLL and thymoma, the proliferating lymphocytes were diffusely distributed and were predominately T cells. Therefore, differentiation of the causes of lymphocytosis should include evaluation of signalment, concurrent disease conditions, lymphocyte morphology, lymphocyte distribution in bone marrow, and immunophenotype. Cat age, presence of severe anemia, and evidence of inflammatory disease also should be considered.     

Hemophagocytosis and Histoplasma‐like fungal infection in 32 cats

Histoplasmosis is one of the most common systemic fungal diseases in cats from the United States. It commonly causes respiratory or disseminated disease and is often associated with one or more cytopenias. Here, we describe 32 cats in which a Histoplasma‐like fungal infection was associated with concurrent hemophagia in at least one sample site, commonly spleen, bone marrow, liver, and/or lymph node. The degree of hemophagia was characterized as moderate or marked in the majority of cases, and in all cases, there was a predominance of phagocytized mature erythrocytes. A few cases also had macrophages with phagocytized erythroid precursors, platelets, and/or neutrophils. Complete blood count results were available for 25 cats, and cytopenias were common (20/25), including solitary anemia (10), anemia and thrombocytopenia (5), solitary neutropenia (2), pancytopenia (2), and anemia and neutropenia (1). Bone marrow samples were only available in a small subset of cases, preventing the further assessment of the causes of the cytopenias. Hemophagocytosis has been previously reported in cats with neoplastic diseases and a cat with calicivirus infection, and likely occurs with other conditions as well, such as hemorrhage or hemolysis. Results of this report suggest that systemic fungal disease is an additional differential to consider when there is hemophagia in a feline cytology sample.     

Myelofibrosis in the dog: three case reports

Myelofibrosis has been reported infrequently in dogs. The pathological features of three dogs with this disease are described. All three animals were presented clinically with non-regenerative anaemia. In two dogs, the neoplastic disorder was unaccompanied by other myeloproliferative disease and was characterized histologically by extensive replacement of normal bone marrow elements by proliferating reticulum cells and myeloid metaplasia of the enlarged liver and spleen. In one animal, focal myeloid metaplasia were also present in the lungs. In the third dog, myelofibrosis was accompanied by erythraemic myelosis and in this animal immature erythroid cells were present in blood, bone marrow, liver and spleen.     

Hemophagocytic syndrome in dogs: 24 cases (1996-2005)

OBJECTIVE: To determine the frequency, potential causes, and clinical and clinicopathologic features of hemophagocytic syndrome in dogs. DESIGN: Retrospective study. ANIMALS: 24 client-owned dogs. PROCEDURES: Records for dogs in which diagnostic bone marrow specimens (including an aspiration smear and core biopsy material) were obtained from 1996 to 2005 were reviewed. Inclusion criteria were presence of bicytopenia or pancytopenia in the blood and > 2% hemophagocytic macrophages in the bone marrow aspirate. RESULTS: Of 617 bone marrow specimens evaluated, evidence of hemophagocytic syndrome was detected in 24 (3.9%). The Tibetan Terrier breed was overrepresented among dogs with hemophagocytic syndrome. Clinical signs associated with hemophagocytic syndrome included fever, icterus, splenomegaly, hepatomegaly, and diarrhea. Hemophagocytic syndrome was associated with immune-mediated, infectious, and neoplastic-myelodysplastic conditions and also occurred as an idiopathic condition. Overall, dogs with infection-associated hemophagocytic syndrome had better 1-month survival rates than dogs with immune-associated and idiopathic hemophagocytic syndrome. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that hemophagocytic syndrome may occur more frequently in dogs than has previously been suspected on the basis of the paucity of reported cases. Although most dogs had definable underlying disease conditions, idiopathic hemophagocytic syndrome was also identified. Hemophagocytic syndrome of any cause is potentially life-threatening; however, the prognosis should be adjusted on the basis of the associated disease process and potential for successful treatment.     

Histopathological and hematological findings in myeloid leukemia induced by a new feline leukemia virus isolate

Myeloid leukemia was induced by a new feline leukemia virus isolate FeLV-AB/GM-1 in a high proportion of cats. The latency period was short. Three to 5 weeks after infection early changes were detectable in the bone marrow, and cats developed leukemia 5 to 8 weeks after infection. The results of the present histological and cytological studies suggested that there were two stages in the development of leukemia. The first stage appeared to be equivalent to the syndrome of bone marrow dysplasia or preleukemia which, however, converted rapidly to leukemia. Cytopenia(s) were the main hematological findings in all preleukemic and leukemic cats. White blood cell counts were low or normal, but the number of leukemic and abnormal cells increased in the peripheral blood with the progression of the disease. This reliable model system lends itself to further studies to elucidate the pathogenesis of myeloproliferative disorders.     

Clinicopathological features of seven cases of canine myelofibrosis and the possible relationship between the histological findings and prognosis.

Seven dogs with non-regenerative anaemia were diagnosed as having myelofibrosis on the basis of the presence of collagen and increased deposits of reticulin fibre in the haemopoietic spaces of bone marrow core biopsies. A scoring system was used to assess the cellularity of the marrow and the amounts of collagen, reticulin and haemosiderin present. These scores, together with the haematological findings, were compared with the dogs' responses to treatment and their outcome. Treatment consisted of blood transfusions, where required, and anabolic steroids and corticosteroids. Three dogs deteriorated and were euthanased within three months of diagnosis, but the other four recovered fully. There was no correlation between the collagen and reticulin scores, or the degree of anaemia and the outcome, but the four dogs which recovered all had a macrocytosis when first examined. There was no evidence of an underlying lymphoproliferative or myeloproliferative disease in any of the seven cases.     

Myeloproliferative disorders

Myeloproliferative disorders are uncommon in the dog and may be classified as chronic or acute. Excessive proliferation of mature cells leads to an overproduction of terminally differentiated blood cells (chronic MPD). Inability of cells to mature results in the accumulation of poorly differentiated blast cells in the peripheral blood and bone marrow (acute MPD). Because the lesion appears to be at the level of the hematopoietic stem cell, all cell lines in the bone marrow may be affected. Diagnosis depends upon the accurate identification of neoplastic cells and the absence of other diseases associated with bone marrow hyperplasia. The prognosis for chronic MPD is guarded, whereas for acute MPD it is grave. Accurate identification of these disorders in animals is important. Investigation and greater understanding of the pathophysiologic mechanisms may lead to more lasting therapeutic successes in the future.     

Estrogen-induced myelotoxicity in dogs: A review

Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone marrow toxicity in dogs. The condition is characterized by hematologic abnormalities including thrombocytopenia, anemia, and leukocytosis or leukopenia. Despite intensive therapy with blood or platelet-rich transfusions, broad-spectrum antibiotics, steroids, and bone marrow stimulants, prognosis is unfavorable. Due to the the risk of stimulating the development of uterine diseases and the potential for inducing aplastic anemia, estrogen use in dogs is best avoided where possible. This paper describes the causes of estrogen-induced myelotoxicity, the clinical presentation of the patients, the diagnosis, and the treatment options in the dog.     

Respiratory diseases of rodents.

Practitioners may be called on to treat rodents with respiratory diseases or to advise clients concerning the care of these rodents. Respiratory diseases of mice, rats, guinea pigs, and Syrian hamsters are well known because of the use of these species in research, whereas few or no reports of respiratory disease in rodents of other species exist. Features of the respiratory diseases of these four commonly encountered species are reviewed, including causes; clinical signs; diagnostic procedures; preventive measures; and, where appropriate, therapies.     

Idiopathic pure red cell aplasia and nonregenerative immune-mediated anemia in dogs: 43 cases (1988-1999)

OBJECTIVE: To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA) and idiopathic nonregenerative immune-mediated anemia (NRIMA). DESIGN: Retrospective study. ANIMALS: 43 dogs with severe nonregenerative anemia. PROCEDURE: Medical records of dogs determined to have PRCA, NRIMA, or ineffective erythropoiesis on the basis of bone marrow analysis between 1988 and 1999 were reviewed. Criteria for inclusion were > or = 5-day history of severe nonregenerative anemia (Hct < 20%; < 60.0 x 10(3) reticulocytes/microliter) with no underlying diseases. Information was retrieved on signalment, clinical signs, laboratory test results, treatment, and outcome. RESULTS: Median age of the dogs was 6.5 years. Spayed females and Labrador Retrievers were significantly overrepresented. Median Hct was 11% with no evidence of regeneration (median, 1.5 x 10(3) reticulocytes/microliter). Direct Coombs' test results were positive in 57% of dogs. Biochemical abnormalities included hyperferremia and high percentage saturation of transferrin. Bone marrow findings ranged from PRCA (5%) to erythroid hyperplasia (55%). Myelofibrosis was common. Dogs were treated with immunosuppressive drugs and the response was complete, partial, and poor in 55, 18, and 27% of the dogs, respectively. Mortality rate was 28%. CONCLUSIONS AND CLINICAL RELEVANCE: An immune-mediated pathogenesis should be considered in dogs with severe, nonregenerative anemia, normal WBC and platelet counts, hyperferremia, mild clinical signs, and no evidence of underlying disease. Bone marrow findings range from the rare PRCA to erythroid hyperplasia. Myelofibrosis is often detected in affected dogs and may prevent bone marrow aspiration.