Bone marrow hypoplasia in eight dogs with Sertoli cell tumor

Eight male dogs with Sertoli cell tumor had pancytopenia and bone marrow hypoplasia attributed to endogenous estrogen myelotoxicosis. Clinical signs were hemorrhage caused by thrombocytopenia, anemia caused by blood loss or diminished erythrocyte production, and infection and fever associated with granulocytopenia. Other signs attributed to hyperestrogenism were feminization and prostatic disease. Two dogs recovered after castration and supportive treatment, but 5 other similarly treated dogs died of hematopoietic failure. One dog was euthanatized.     

Primary myelodysplastic syndromes of dogs: a report of 12 cases

Clinical bone marrow specimens submitted to the University of Minnesota's Veterinary Teaching Hospital Cytology Service over a 3-year period were evaluated for the presence of myelodysplastic features. Of 220 bone marrow specimens examined, 30 contained dysplastic features. Twenty-seven of these dogs were evaluated further. Twelve were categorized as primary myelodysplastic syndromes, and 15 were categorized as secondary myelodysplastic syndromes. Of the primary myelodysplastic syndromes, 4 were subcategorized as refractory anemia and 8 were categorized as myelodysplasia. Primary refractory anemia was characterized by nonregenerative anemia without leukopenia or thrombocytopenia and with prolonged survival. Primary myelodysplasia was characterized by pancytopenia, greater than 5% myeloblasts in bone marrow, dysplastic features in all bone marrow cell lines, and short survival time. Results of this study indicate that differentiating primary refractory anemia from primary myelodysplasia has both therapeutic and prognostic significance. Dogs with primary refractory anemia tend to have prolonged survival and respond to erythropoietin treatment, whereas dogs with primary myelodysplasia have short survival and do not respond to standard treatments.     

Cytologic evaluation of primary and secondary myelodysplastic syndromes in the dog

Myelodysplastic syndromes are a heterogeneous group of acquired primary and secondary alterations of hematopoietic stem cells that result in cytopenias in blood and cytologic features of dysplasia in blood and/or bone marrow. To better understand the cytologic features that would permit differentiation of primary and secondary forms of myelodysplasia, we reviewed 267 consecutive bone marrow reports from dogs. These reports indicated that 34 dogs (12.7%) had dysgranulopoiesis, dyserythropoiesis, and/or dysthrombopoiesis in >10% of granulopoietic cells, erythroid cells, and/or megakaryocytes, respectively. Thirteen dogs had primary myelodysplastic syndromes, and 21 had secondary myelodysplastic syndromes. Of the 13 dogs with primary myelodysplasia, 4 were subclassified as myelodysplastic syndrome with refractory anemia (MDS-RA), and 9 were subclassified as myelodysplastic syndrome with excess blasts (MDS-EB). Secondary conditions associated with dysplasia in the bone marrow included malignant lymphoma (n = 5), myelofibrosis (n = 3), immune-mediated thrombocytopenia (n = 4), immune-mediated hemolytic anemia (n = 5), multiple myeloma with melphalan administration (n = 1), pyometra with estrogen administration (n = 1), polycythemia vera (n = 1), and thrombopathia (n = 1). MDS-RA was characterized by <5% myeloblasts in bone marrow, normal granulocyte maturation ratio, increased erythroid maturation ratio, and dysplastic changes in >15% of erythroid cells. MSD-EB was characterized by >/=5% myeloblasts in bone marrow, high granulocyte maturation and erythroid maturation ratios, >/=32% dysplastic granulocytes, and the presence of small atypical immature myeloid cells. Secondary myelodysplastic syndromes were characterized by <5% myeloblasts in bone marrow, variable granulocyte maturation and erythroid maturation ratios, and variable dysplastic features. These results indicate that morphology alone cannot be used to distinguish primary and secondary myelodysplastic syndromes in dogs.     

Effect of canine parvovirus on erythroid progenitors in phenylhydrazine-induced regenerative hemolytic anemia in dogs

The effects of canine parvovirus (CPV) infection in dogs with hemolytic anemia was compared with the clinical effects of human parvovirus-induced aplastic anemia in human beings with chronic regenerative anemias. Phenylhydrazine was used to induce a transient, severe, hemolytic anemia in dogs to evaluate the effects of CPV infection on rapidly dividing bone marrow precursors. Erythrocyte colony-forming unit bone marrow cultures and cytologic examination of bone marrow were used to determine the effects of CPV infection on erythroid bone marrow precursors. The induced hemolytic anemia regenerated rapidly and although the bone marrow was infected, it was determined that CPV infection did not induce a detectable decrease in erythroid progenitors in dogs with severe hemolytic anemia.     

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.     

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.     

Primary pure red cell aplasia in dogs: 13 cases (1996-2000)

OBJECTIVES: To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA). DESIGN: Retrospective study. ANIMALS: 13 dogs with severe nonregenerative anemia and bone marrow erythroid aplasia. PROCEDURES: Medical records of dogs determined to have PRCA on the basis of results of blood and bone marrow analysis between 1996 and 2000 were reviewed. Criteria for inclusion in the study were severe nonregenerative anemia (Hct < 20%; reticulocyte count < 1.0%), selective erythroid aplasia in bone marrow, and lack of underlying diseases that may have caused the anemia. RESULTS: Median age of dogs was 6.5 years. Females were significantly overrepresented. Median Hct was 10%, and median reticulocyte count was 0.1%. Direct Coombs' test results were negative for all dogs tested, and spherocytosis was evident in 2 dogs. All dogs were treated with prednisolone, and 2 dogs were treated with prednisolone and cyclophosphamide. Responses to treatment were complete, partial, and poor in 10, 1, and 2 dogs, respectively. Median time required to achieve an increase of 5% or more in Hct was 38 days, and median time to complete remission was 118 days. Of 10 dogs for which follow-up information was available, only 1 required long-term immunosuppressive treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with PRCA appear to respond readily to treatment with immunosuppressive drugs; however, hematologic responses may not be observed for weeks to months after initiation of treatment.     

Cephalosporin-induced changes in the ultrastructure of canine bone marrow

Fourteen healthy dogs were given 540 to 840 mg/kg of cefazedone (Refosporen) intravenously for up to 4 months or until peripheral blood cell count were depressed. Within 6 to 10 weeks treated dogs developed pancytopenia (5/14), thrombocytopenia (11/14), moderate to severe neutropenia (8/14), and/or normocytic anemia with erythroblastemia (8/14). Ultrastructural changes in bone marrow of severely cytopenic dogs included mitochondrial damage in hematopoietic and nonhematopoietic cells, thickening of endosteal bone lining layers, increased adventitial coverage of vascular sinuses, and an increased number of active macrophages. Swollen, ruptured mitochondria were in erythroid, granulocytic, and megakaryocytic cells, and, to a lesser extent, in macrophages, reticular endothelial, and bone lining cells. Maturation arrest was evident in both erythroid and granulocytic cell lines. There was also evidence of ineffective erythropoiesis and granulopoiesis. None of these changes were observed in bone marrow of controls, treated dogs that did not develop cytopenia, or dogs allowed to recover after cessation of dosing.     

Sideroblastic anemia in 7 dogs (1996-2002)

Sideroblastic anemia is an anemic condition characterized by chronic hypochromic anemia and the presence of large iron deposits in erythroid cells. Seven dogs with sideroblastic anemia were evaluated retrospectively. Historical, clinical, and clinicopathologic findings were reviewed to determine whether the condition was idiopathic or associated with disease conditions or drug or toxin exposure. Associated diseases were identified in 6 affected dogs and included acute hepatitis, pancreatitis, acute hepatitis and pancreatitis, inflammatory disease, glomerulonephritis, and myelofibrosis. None of the dogs had a history of recent exposure to drugs or toxins. One dog had no evidence of associated disease. Regardless of the associated disease condition, sideroblastic anemia was characterized by moderate to severe nonregenerative and frequently hypochromic anemia with prominent dysplastic features in bone marrow that were most prominent in the erythroid series. Survival varied from days to years. Identification of large numbers of siderocytes or sideroblasts in blood or bone marrow is inconsistent with a diagnosis of iron deficiency and should prompt a search for inflammatory disease conditions, including hepatitis, pancreatitis, and glomerulonephritis.     

Chronic lymphopenia and neutropenia in a dog with large granular lymphocytic leukemia

T‐cell large granular lymphocytic leukemia (T‐cell LGLL) is the most common presentation of chronic lymphocytic leukemia (CLL) in dogs. Aleukemic or subleukemic leukemia is a particularly rare variation in both humans and dogs, where bone marrow proliferation is either not or only sparsely translated in the peripheral blood. Neutropenia is a prominent feature in cases of human T‐cell LGLL but is normally absent in canine CLL. This report describes a case of a dog presented with an almost 3‐year history of asymptomatic neutropenia, lymphopenia, and thrombocytopenia (without anemia). A bone marrow examination, the exclusion of infectious diseases, and clonality testing led to the diagnosis of subleukemic LGLL that responded well to therapy (death occurred 2.5 years later due to an unrelated cause).     

Bone marrow hypoplasia in a feminized dog with an interstitial cell tumor.

Bone marrow hypoplasia and feminization developed in a 10-year-old male German Shepherd Dog with interstitial cell tumor. Clinical abnormalities included pyrexia, pale mucous membranes, signs of abdominal pain, large left testis, atrophied right testis, and feminization. Abnormal laboratory findings included pancytopenia, bacteremia, bacteriuria, and pyuria. Results of cytologic examination of a bone marrow aspirate were consistent with aplastic anemia. Serum estradiol concentration was high, and serum testosterone concentration was low, compared with normal values for male dogs. The left testicular mass was identified as an interstitial cell tumor. Other causes of the aplastic anemia or feminization were not found.     

Idiopathic aplastic anemia in a dog

A case of idiopathic aplastic anemia in a dog was characterized by pancytopenia and bone marrow aplasia. Erythroid colony-forming units (CFU-E) were not detected in bone marrow culture. Addition of the dog's serum to CFU-E culture from control dogs failed to suppress colony formation, suggesting that humorally-mediated suppression at the CFU-E level was not a cause of the aplastic anemia.     

Malignant histiocytosis in four dogs

The clinical and pathologic features of 4 dogs with malignant histiocytosis were evaluated. The most common clinical signs were weight loss, lethargy, lymphadenopathy, hepatosplenomegaly, and anemia. Neoplastic histiocytic infiltrates most commonly were found in the spleen, bone marrow, liver, or lymph nodes. Malignant histiocytosis was considered as a differential diagnosis for anemic dogs with lymphadenopathy and/or hepatosplenomegaly.     

Myelofibrosis: Review of clinical and pathological features in fourteen dogs

A clinicopathological study was performed on 14 dogs with myelofibrosis (MF), in order to correlate clinical, laboratory, and histomorphological parameters and investigate factors of prognostic significance. The clinical signs included fatigue, weight loss, anorexia, and diarrhea. Physical findings included pale mucous membranes and wasting/emaciation. The major laboratory observations were moderate to severe, poorly-responsive anemia with various degrees of marrow cellularity and fibrosis. All dogs with severe, non-responsive anemia should have a bone marrow core biopsy, stained for connective tissue, in order to detect myelofibrosis. Myelofibrosis regressed in six dogs.     

Clinicopathological findings and results of bone marrow aspiration in dogs with cutaneous mast cell tumours: 157 cases (1999–2002)*

Bone marrow aspiration for routine staging of canine cutaneous mast cell tumour is not consistently performed, and the overall incidence of bone marrow infiltration and predictive value of the complete blood count (CBC) is unknown. This study evaluated a series of 157 dogs presented for cutaneous mast cell tumours in which a CBC and bone marrow aspiration were performed. The incidence of bone marrow infiltration at initial staging was low at 2.8%, and 4.5% overall. Factors significantly associated with bone marrow infiltration included increased age, leucocytosis, anaemia, neutrophilia, monocytosis, eosinophilia, thrombocytopenia, being purebred and staging at the time of recurrent or progressive disease. Our study suggests that a bone marrow sample is not indicated for routine staging but maybe indicated for those dogs with mast cell tumours having either an abnormal haemogram (neutrophilia, monocytosis, eosinophilia, basophilia, anaemia and thrombocytopenia) or presenting for tumour regrowth, progression or new occurrence.     

Canine hemophagocytic histiocytic sarcoma: a proliferative disorder of CD11d+ macrophages

Histiocytic disorders of dogs include histiocytoma, localized histiocytic sarcoma (HS), disseminated HS (malignant histocytosis), and the reactive histiocytoses: cutaneous and systemic. A common element to these diseases is proliferation of dendritic cells (DC) of either Langerhans cell (epithelial DC) or interstitial DC lineage. In this report, 17 dogs with hemophagocytic HS are described. Breeds affected included Bernese Mountain Dog (6), Golden Retriever (4), Rottweiler (3), Labrador Retriever (2), a mixed-breed dog, and a Schnauzer, which were from 2.5 to 13 years old. The dogs presented with Coombs negative responsive anemia in 16/17 dogs (94%), thrombocytopenia in 15/17 dogs (88%), hypoalbuminemia in 16/17 dogs (94%), and hypocholesterolemia in 11/16 dogs (69%). All dogs died or were euthanized. The clinical course ranged from 2 to 32 weeks (mean 7.1 weeks). Diffuse splenomegaly with ill-defined masses was consistently present. Microscopic lesions were prevalent in spleen, liver, lung, and bone marrow. Metastasis occurred by insidious intravascular invasion with minimal mass formation. Histiocytes were markedly erythrophagocytic and accompanied by foci of extramedullary hemopoiesis. Cytologically, the histiocytes varied from well differentiated to atypical, with atypia more prevalent in spleen than bone marrow. These tumors arose from splenic red pulp and bone marrow macrophages, which expressed major histocompatibility complex class II and the beta2 integrin, CD11d. They had low and/or inconsistent expression of CD1 and CD11c, which are dominantly expressed by canine nonhemophagocytic HS of DC origin. Canine histiocytic proliferative diseases now encompass proliferation of all members of the myeloid histiocytic lineage: Langerhans cells, interstitial DC, and macrophages.     

Bone marrow necrosis and myelophthisis: manifestations of T‐cell lymphoma in a horse

Abstract: A 14‐year‐old spayed American Paint mare was evaluated for mild colic, anorexia, pyrexia, and pancytopenia. Physical examination revealed mild tachycardia, tachypnea, and pale mucous membranes. Serial laboratory analyses revealed progressive pancytopenia, hyperfibrinogenemia, and hyperglobulinemia. A few large atypical cells were observed in peripheral blood smears. Results of tests for equine infectious anemia and antipenicillin antibody were negative. Serum protein electrophoresis indicated a polyclonal gammopathy. Smears of bone marrow aspirates contained hypercellular particles, but cell lines could not be identified because the cells were karyolytic, with pale basophilic smudged nuclei and lack of cellular detail. A diagnosis of bone marrow necrosis was made. Treatment consisted of antimicrobials, nonsteroidal anti‐inflammatory drugs, and corticosteroids. The pyrexia resolved; however, the pancytopenia progressively worsened and petechiation and epistaxis developed. The horse was humanely euthanized. Postmortem examination revealed a diffuse round cell neoplasm infiltrating the kidneys, spleen, lymph nodes, lungs, and bone marrow. Immunophenotyping results (CD3+, CD79α−) indicated the neoplastic cells were of T‐cell lineage. Infiltration of lymphoma cells into the bone marrow appeared to have resulted in severe myelophthisis and bone marrow necrosis. Bone marrow necrosis has been associated previously with lymphoma in humans and dogs. To our knowledge, this is the first reported case of lymphoma resulting in bone marrow necrosis in a horse.     

Flow cytometric evaluation of hemophagocytic disorders in canine

Background — Hemophagocytic macrophages in canine bone marrow are observed in malignant histiocytosis as well as benign hemophagocytic histiocytosis. Cytomorphologic evaluation alone may be inadequate to consistently differentiate between benign and malignant forms of hemophagocytic disorders. Objective — The purpose of this study was to evaluate the ability of flow cytometry and immunophenotyping to differentiate between benign and malignant types of hemophagocytic disorders in dogs. Methods — Blood smears and bone marrow differential cell counts were evaluated for 10 dogs with hemophagocytic disorders. Bone marrow samples were labeled with monoclonal antibodies to CD18, MCH class‐II, Thy‐1, CD14, CD3, and CD21. Using flow cytometry, forward‐angle versus side‐angle light scatter plots were analyzed and immunophenotypes were determined. Results — Scatter plots from 3 dogs with a necropsy diagnosis of malignant histiocytosis revealed 2 atypical cell clusters. One cluster contained cells of similar size or larger than immature myeloid cells and metamyelocytes. Cells in the other cluster were highly granular, with granularity similar to or greater than that of metamyelocytes. In bone marrow from dogs with malignant histiocytosis that was labeled with anti‐CD14 antibody, macrophages represented 29–48% of nucleated cells. Seven dogs had a clinical or histopathologic diagnosis of benign hemophagocytic syndrome. Three of the dogs had normal cell distribution in scatter plots. Two dogs had 2 abnormal cell clusters: 1 within the immature myeloid and metamyelocyte gates and the other with granularity similar to or greater than that of metamyelocytes. The remaining 2 dogs had an atypical cell population, mostly within the immature myeloid gate. For dogs with benign hemophagocytic syndromes, 6–17% of cells in the bone marrow were CD14 positive. Conclusions — The cellular distribution in scatter plots and the total number of macrophages in bone marrow may be useful in differentiating malignant histiocytosis from benign hemophagocytic syndromes in dogs.     

Disseminated histoplasmosis in dogs: 12 cases (1981-1986)

Diarrhea, intestinal blood loss, anemia, and lethargy were predominant clinical findings in 12 dogs with disseminated histoplasmosis. Young dogs were affected most commonly, with 6 dogs being 1 to 3 years old. A diagnosis of disseminated histoplasmosis was established on the basis of histologic or cytologic detection of Histoplasma organisms in intestinal or rectal mucosa in 7 dogs, in circulating leukocytes in 5 dogs, in bone marrow in 3 dogs, and in multiple tissues at necropsy in 1 dog (4 dogs had Histoplasma organisms detected in greater than 1 site). Anemia was detected in 10 dogs (PCV less than 20% in 3 dogs), and the anemia was inadequately regenerative or nonregenerative in 7. Hypoalbuminemia was detected in 9 dogs, and serum albumin concentrations were low (less than 1.0 g/dl) in 4 of the 9 dogs. Of 5 dogs treated with ketoconazole, 2 were in remission for greater than or equal to 1 year. Corticosteroid therapy may have exacerbated the disease in 4 dogs. Histoplasma infection of multiple organs was detected in 5 necropsied dogs.     

Anemia of inflammation in dogs infected with Ehrlichia platys

Ten adult male dogs were inoculated with Ehrlichia platys, and blood samples were collected throughout the infection to evaluate the hematologic changes with respect to serum biochemical analytes. All dogs developed a mild, normocytic, normochromic anemia by postinoculation day 7, with significantly (P less than 0.05) decreased serum iron concentration and total iron-binding capacity. Stainable bone marrow iron appeared normal or increased throughout the infection. By postinoculation day 31, the PCV was not significantly different from the pretreatment value. All dogs became hypergammaglobulinemic, leukopenic, hypoalbuminemic, and hypocalcemic during the infection. These findings were compatible with the syndrome of anemia of inflammation.