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.     

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.     

Zollinger-Ellison syndrome and myelofibrosis in a dog

Zollinger-Ellison syndrome and myelofibrosis were diagnosed concurrently in a 10-year-old neutered female Brittany Spaniel. Documentation of gastric ulceration, hypergastrinemia, and gastrin-secreting islet cell tumor with splenic metastases facilitated the diagnosis of Zollinger-Ellison syndrome. Patchy long-bone medullary sclerosis, nonregenerative anemia and thrombocytopenia, multiple acellular bone marrow aspirates, marked splenic extramedullary hematopoiesis, and acellular core bone marrow biopsy with areas of necrosis and fibrosis supported the diagnosis of myelofibrosis. Despite the medical and surgical management attempted, the dog was euthanatized because of signs of severe intractable bone pain. Myelofibrosis has been documented in association with canine and human neoplastic disease. A direct causal relationship between gastrinoma and myelofibrosis was not clearly established in this instance.     

An appraisal of bone marrow biopsy in assessment of sick dogs.

Dogs were classified into a number of disease categories according to hematological, cytological and serochemical changes. Aspiration and core bone marrow biopsies were examined in 128 dogs in the various disease categories and compared to marrow samples in 36 dogs which appeared clinically normal. Differential cell counts on bone marrow smears were examined in relation to the blood variables in all animals. Blood and bone marrow data (group means) were compared among the normal and disease groups. Anemia, responsive and poorly responsive was the most frequent blood abnormality. Most dogs in the thrombocytopenia group had increased numbers of megakaryocytes in the marrow but two dogs had a marked decrease. The frequency of serious alteration of marrow production of the erythroid, myeloid and megakaryocytic series was less than anticipated. Marrow hemopoiesis was not significantly compromised in dogs with lymphoma or in dogs with other types of cancer. Bone marrow examination was necessary for the diagnosis of myelofibrosis and pancytopenia and was very helpful in the groups with insufficient change in the blood to permit a definitive diagnosis to be made. The myeloid-erythroid ratio was a useful indicator of marrow response while the erythroid maturation index and the myeloid maturation index were useful for identification of altered patterns of maturation (ineffective hemopoiesis). The reticulocyte response in absolute numbers is the most efficient and clinically relevant measure of erythroid response.     

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.     

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.     

Pulmonary aspergillosis in a horse with myelomonocytic leukemia

Acute myelomonocytic leukemia was diagnosed in a 2-year-old Standardbred mare that had hind limb edema and fever unresponsive to antibiotics. The mare had anemia, thrombocytopenia, and leukocytosis, with circulating myeloblasts and monocytoid cells. A bone marrow specimen was hypercellular, with myeloblasts and monocytoid cells. Peroxidase, chloroacetate esterase, and alpha naphthyl acetate esterase activities were detected in many bone marrow cells. Interstitial pulmonary densities were seen radiographically. The mare was euthanatized and necropsied. Infiltrates of leukemic cells were found microscopically in specimens of spleen, lymph nodes, liver, kidneys, gastrointestinal tract, and lungs. Granulomas containing fungal hyphae were seen microscopically in the lungs, and Aspergillus sp was isolated from the lesions.     

Pancytopenia Secondary to Lymphoid Leukemia in Three Horses

Pancytopenia was observed in two 3-year-old geldings and one 11-year-old mare. All horses had a brief history (2 days to 4 weeks) of fever, anorexia, and depression. One of the three horses had blast cells present on a peripheral blood smear. Examination of the bone marrow showed substantial infiltration with neoplastic lymphoid cells. At necropsy, neoplastic cells were restricted to the bone marrow in one horse, present in bone marrow, liver, and spleen in the second horse, and reported in multiple tissues in the third horse, including bone marrow, kidneys, lung, myocardium and lymph nodes. The value of a bone marrow aspirate and core biopsy in the investigation of pancytopenia is highlighted. (Journal of Veterinary Internal Medicine 1993; 7:360–363. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

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.     

A retrospective study of 19 cases of canine myelofibrosis

Nineteen cases of myelofibrosis were identified among 456 canine bone marrow specimens submitted for analysis. Myelofibrosis was classified as primary in I dog and as secondary in 18 dogs. Clinical conditions associated with secondary myelofibrosis included immune-mediated hemolytic anemia (n = 5), neoplasia (n = 4), and long-term drug treatment (n = 4). Drugs administered included phenobarbital, phenytoin, phenylbutazone, and colchicine. Bone marrow necrosis was observed in 5 dogs. Eight dogs were treated with immunosuppressive doses of prednisolone, and 3 were treated with erythropoietin. Half of the dogs with secondary myelofibrosis recovered from their cytopenias and were alive from 4 months to 5 years after diagnosis.     

Aplastic anemia in cats - clinicopathological features and associated disease conditions 1996-2004

A retrospective study of 128 feline bone marrow reports identified 13 cases of aplastic anemia. Clinical diagnoses included chronic renal failure (n=5), feline leukemia virus infection (n=2), hyperthyroidism treated with methimazole (n=1) and idiopathic aplastic anemia (n=5). In some cats, starvation may play a role in the development of marrow aplasia. Some cats with aplastic anemia can have prolonged survival without resolution of the pancytopenia.     

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.     

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.     

Familial nonspherocytic hemolytic anemia in poodles

Nonspherocytic hemolytic anemia, characterized by marked reticulocytosis, hepatosplenomegaly, hemosiderosis of reticuloendothelial organs and bone marrow myelofibrosis, and osteosclerosis, was diagnosed in 5 related Poodles. The unremitting anemia was clinically evident by 1 year of age, and was fatal as early as 3 years of age. Despite intense diagnostic endeavors including RBC fragility studies, RBC enzyme assays, and hemoglobin electrophoresis, the cause of this nonspherocytic hemolytic anemia remains to be determined.     

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.     

Presumed generalised seizure following caudal epidural administration of morphine and detomidine in a pony

A 9-year-old show pony mare became acutely lame following removal of a bone sequestrum of the distal phalanx of the right thoracic limb. The mare also suffered from ongoing right dorsal colitis secondary to previous long-term nonsteroidal anti-inflammatory drug (NSAID) use. To avoid further NSAID use, a protocol for caudal epidural administration of morphine and detomidine in an increased volume was used to provide analgesia to the thoracic limbs. A total volume of 50 mL (0.2 mL/kg bwt) was administered over approximately 90 s. Immediately following the injection, the pony collapsed into lateral recumbency and experienced an apparent generalised seizure characterised by loss of consciousness and frantic paddling of all four limbs. The pony recovered rapidly without intervention, and no residual neurological deficits were noted. The epidural analgesia resulted in a marked improvement in comfort levels. The speed of injection is thought to have caused a change in epidural and intracranial pressures resulting in a generalised seizure and highlights the importance of administering large volumes slowly.     

Secondary myelofibrosis in three dogs

Myelofibrosis was diagnosed in 3 dogs. In each dog, there was evidence of concurrent bone marrow necrosis, suggesting that the myelofibrosis was a secondary change. This suggestion was supported by a lack of dysplastic changes in hematopoietic cells. Bone marrow necrosis in 2 of the dogs may have been the result of widespread malignancy. Reversal of the myelofibrosis in 1 dog suggested that myelofibrosis is not always a terminal disorder.     

Pancytopenia with bleeding tendency associated with bone marrow aplasia in a Holstein calf

An 11-day-old Holstein calf presented with a high rectal temperature and tachypnea. Treatment with antibiotics and non-steroidal anti-inflammatory drugs did not improve the clinical signs. Bleeding tendency, with several hemorrhage spots on the body surface, appeared five days after admission. Severe pancytopenia was observed in the blood examination. The calf died on the 11th day after admission with severe bleeding from an injection site. Necropsy findings revealed that the pancytopenia had resulted from severe bone marrow aplasia. A congenital disorder was suspected to be the cause of pancytopenia associated with bone marrow aplasia.     

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.     

A retrospective study of canine pancytopenia

To better define the incidence and causes of canine pancytopenia, we retrospectively evaluated the results of complete blood counts submitted to the University of Minnesota Veterinary Teaching Hospital during a 1-year period. Pancytopenia was defined as packed cell volume < 36%, total leukocyte count < 6,000/microliter or total segmented neutrophil count < 3,000/microliter, and platelet count < 200,000/microliter. Of 4,560 complete blood counts, 110 (2.4%) samples from 51 dogs met the criteria for pancytopenia. Eleven different disease processes were identified. These included chemotherapy-associated pancytopenia (n=22), parvovirus infection (n=5), malignant histiocytosis (n=5), idiopathic aplastic anemia (n=3), sepsis (n=3), myelodysplastic syndrome (n=3), immune-mediated hematologic disease (n=3), lymphoblastic leukemia (n=2), ehrlichiosis (n=2), estrogen toxicity (n=2), and multiple myeloma (n=1). Malignant histiocytosis and idiopathic aplastic anemia occurred more frequently than was expected. Doxoruicin was the chemotherapeutic agent associated with pancytopenia. Hematologic recovery and patient survival time varied with the cause of pancytopenia; therefore, a specific diagnosis was essential for establishing prognosis. Differentiation among causes of pancytopenia requires a systemic approach that includes elimination of infectious and drug-induced causes, and examination of bone marrow aspiration and core biopsy specimens.