Multiple myeloma in a horse

Multiple myeloma was diagnosed in a 22-year-old Arabian mare with a history of chronic weight loss. Quantitative immunoglobulin analysis revealed monoclonal gammopathy (IgG(T), 9,800 mg/dl). Due to progressive weight loss, the horse was euthanatized. Microscopy of tissues revealed plasma cell infiltrates in bone marrow, spleen, pituitary gland, adrenal cortex, muscle of the tongue, and bronchial, renal, and mesenteric lymph nodes.     

Lymphoreticular neoplasia in a dog resembling malignant histiocytosis (histiocytic medullary reticulosis) in man.

Malignant histiocytosis was diagnosed in a 4-year-old-dog. Major clinicopathologic findings included multiple cutaneous tumors, peripheral lymphadenopathy, hepatomegaly, lytic bone lesions, anemia, thrombocytopenia, and monoclonal IgA gammopathy. Pathologic findings included multi-systemic infiltration of erythrophagocytic malignant histiocytes. Chemotherapy was unsuccessful.     

Biclonal gammopathy associated with immunoglobulin A in a dog with multiple myeloma

A 10-year-old neutered male Airedale Terrier was evaluated for inappetance, weight loss, and lameness. Multiple myeloma was diagnosed based on bone marrow plasmacytosis, multiple lytic bone lesions, and hyperglobulinemia with a clonal gammopathy on serum protein electrophoresis. Splenic plasmacytosis, and retinal lesions consistent with hyperviscosity syndrome also were found. Temporary responses to 2 different chemotherapy protocols (melphalan and prednisone, and cyclophosphamide and prednisone) were seen, with remission of clinical signs and a decrease in the biclonal gammopathy but no resolution of the splenic mass. Eventual return of clinical signs led to euthanasia at 175 days postdiagnosis. Necropsy examination confirmed multiple myeloma involving bone marrow and spleen, and glomerulonephritis. An immunoglobulin-A (IgA) gammopathy was demonstrated by immunoelectrophoresis; biclonality was ascertained by immunofixation electrophoresis. The clonal components consisted of intact Ig with a heavy chain of the a class and a light chain of undetermined class. To our knowledge, this is the first report of undimerized biclonal gammopathy in a dog caused by a single heavy chain class involving IgA.     

Plasma cell sarcoma in a cat

Lytic lesions occurring in conjunction with plasma cell sarcoma (multiple myeloma) have rarely been reported in cats.

A plasma cell sarcoma was diagnosed in a 13 year old castrated male Siamese cat with hind limb paresis resulting from osteolysis of the second lumbar vertebra. Serum electrophoresis showed a monoclonal gammopathy. A uniform population of plasma cells was found in and around the second lumbar vertebra and in the bone marrow of the femora, humeri, pelvis and the fifth lumbar vertebra. The neoplastic cells were identified as IgA and kappa chain specific by direct immunofluorescence.

     

Multiple myeloma in a horse

Multiple myeloma was diagnosed in a horse on the basis of clinical signs, protein electrophoresis pattern, Bence-Jones proteinuria, and radiographic changes in bone. The horse had mild depression, weight loss, edema of the distal portion of the left hind limb, anemia, hyperproteinemia, and monoclonal gammopathy in the beta 2 region. Radiographically, punctate cortical lysis of bone was seen. Specific treatment for the multiple myeloma was not attempted and the horse was euthanatized.     

Elevated fructosamine concentrations caused by IgA paraproteinemia in two dogs

An 8-year-old male Austrian Pinscher and a 14-year-old male Golden Retriever were presented for evaluation due to unexplainable high fructosamine values despite euglycemia and epistaxis in combination with polydipsia/polyuria, respectively. Blood analysis revealed severe hyperglobulinemia, hypoalbuminemia and markedly elevated fructosamine concentrations in both dogs. Multiple myeloma with IgA-monoclonal gammopathy was diagnosed by serum and urine electrophoresis including immunodetection with an anti-dog IgA antibody and bone marrow aspirations. Diabetes mellitus was excluded by repeated plasma and urine glucose measurements. Fructosamine values were positively correlated with globulin, but negatively correlated with albumin concentrations. These cases suggest that, as in human patients, monoclonal IgA gammopathy should be considered as a possible differential diagnosis for dogs with high fructosamine concentrations.     

Serum hyperviscosity syndrome associated with multiple myeloma in two cats.

Serum hyperviscosity syndrome was diagnosed in 2 cats with multiple myeloma. Clinical signs included pale mucous membranes, dehydration, retinal hemorrhages, dilated and tortuous retinal vessels, seizures, head-tilt, nystagmus, systolic murmur, and gallop rhythm. Laboratory abnormalities included hyperglobulinemia, azotemia, hyperphosphatemia, nonregenerative anemia, and thrombocytopenia. Both cats had IgG monoclonal gammopathy, Bence Jones proteinuria, increased numbers of bone marrow plasma cells, and high values for relative serum viscosity. Renal disease was suspected in both cats. Cardiac hypertrophy was documented in 1 cat and was suspected in the other cat. Chemotherapy, using melphalan, prednisone, and vincristine, caused short-term remission in both cats, and plasmapheresis was used to lower serum protein concentration in 1 cat. Serum hyperviscosity syndrome rarely develops in cats, but should be suspected when monoclonal gammopathy exists with signs of neurologic, cardiac, or retinal disease.     

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.     

Differentiation of Chronic Lymphocytic Leukemia in the Horse: A Report of Two Cases

Chronic lymphocytic leukemia (CLL) was diagnosed in two horses: an 18-year-old Quarter Horse gelding that was examined because of edema of the prepuce and ventral abdomen; and a 20-year-old mixed breed gelding that was referred because of lymphocytosis, ventral edema, and weight loss. The first horse had enlarged peripheral lymph nodes and cool nonpainful pitting edema of the ventral abdomen and prepuce. The second horse had enlarged peripheral lymph nodes, cool nonpainful pitting edema of the ventral thorax and cranial ventral abdomen, and a 3/5 holosystolic heart murmur. The diagnosis of CLL was based on increased blood lymphocyte counts and infiltration of marrow and other tissues by lymphocytes. In horse 1, the lymphocytosis persisted for 2 months between initial examination and death. The results of flow cytometric analysis on blood lymphocytes using anti-lymphocyte antibodies suggested that horse 1 had T-cell CLL, and horse 2 had B-cell CLL. In addition, the second horse had a monoclonal gammopathy (IgG), with light-chain proteinuria.     

Chronic lymphocytic leukemia in the dog: 22 cases (1974-1984)

Chronic lymphocytic leukemia was diagnosed in 22 dogs. Diagnosis was based primarily on detection of lymphocytosis and bone marrow infiltration with small lymphocytes similar to those seen in the blood. More than 50% of the dogs had monoclonal gammopathy, and, of these, 40% had monoclonal light-chain (Bence Jones) proteinuria. Hyperviscosity syndrome was observed occasionally. Most dogs were treated with chemotherapy. For the 17 dogs treated greater than or equal to 30 days, the survival times ranged from 30 to 1,000 days.     

Hypercalcemia and high serum parathyroid hormone-related protein concentration in a horse with multiple myeloma

A 13-year-old gelding was examined because of weight loss, hyperglobulinemia, and hypercalcemia. Possible causes of hypercalcemia that were considered included renal failure, primary hyperparathyroidism, vitamin D toxicosis, and malignancy. There was no history of vitamin D ingestion, and serum creatinine and parathyroid hormone concentrations were normal, making renal failure and primary hyperparathyroidism unlikely. The hypercalcemia was suspected to be a result of malignancy, but thorough testing did not reveal any neoplastic disease. Eight months later, serum parathyroid hormone-related protein (PTHrP) concentration was high, supporting the suggestion that hypercalcemia was a result of malignancy. In addition, radial immunodiffusion confirmed a selective 300-fold increase in serum IgA concentration. The horse was euthanatized, and postmortem examination revealed neoplastic infiltrates in the kidneys, lymph nodes, liver, and bone marrow. Neoplastic cells had morphologic characteristics of plasma cells, and immunohistochemical staining confirmed that neoplastic cells were expressing PTHrP and IgA. The final diagnosis was multiple myeloma with expression of IgA paraprotein.     

ATYPICAL LYTIC PROLIFERATIVE SKELETAL LESIONS ASSOCIATED WITH PLASMA CELL MYELOMA IN A DOG

A 10-year-old female Labrador Retriever with intermittent lameness, lethargy, pancytopenia, hyper-calcemia, and severe hyperproteinemia was diagnosed as having plasma cell myeloma. Diagnosis was confirmed by finding a monoclonal gammopathy, extensive plasmacytic bone marrow infiltration, and radiographic evidence of skeletal disease. Survey radiography revealed atypical lytic proliferative osseous lesions involving the spinous process of the third thoracic vertebrae, left third rib, and both left and right fifth ribs. Nutritional support and specific chemotherapy with Melphalan have resulted in long-term clinical remission. This report describes the radiographic and clinicopathologic features of plasma cell myeloma in the dog. A discussion of the previously reported radiographic features of this neoplasm is also included.     

Hyperviscosity syndrome associated with lymphocytic leukemia in three dogs.

Hyperviscosity syndrome was associated with increased plasma content of monoclonal immunoglobulin (IgA or IgM) in 3 dogs with lymphocytic leukemia. The diagnosis of lymphocytic leukemia was based on the finding of a large number of mature lymphocytes in the blood and bone marrow. The clinical signs included weakness, lethargy, depression, and coughing due to congestive heart failure. Consistent physical findings were splenomegaly, with or without peripheral lymphadenopathy, and funduscopic abnormalities. Of the 2 dogs treated successfully with chlorambucil, 1 remains in remission after withdrawal of the drug for over 1 year.     

Detection of biclonal gammopathy by capillary zone electrophoresis in a cat and a dog with plasma cell neoplasia

Gammopathies associated with plasma cell neoplasms in a 15-year-old female spayed domestic shorthaired cat and a 9-year-old female spayed Rottweiler dog were evaluated by serum protein electrophoresis. In the cat, the plasma cell neoplasm was found in the liver and spleen, and an evaluable sample of bone marrow was not obtained. Some of the plasma cells had the morphologic appearance of flame cells. The paraprotein was confirmed as IgG based on agar gel immunodiffusion precipitation and both immunocytochemical and immunohistochemical staining. The dog had multiple myeloma with production of IgG and IgA paraproteins. In both cases, serum proteins were evaluated by 2 methods of protein electrophoresis: cellulose acetate electrophoresis (CAE) and capillary zone electrophoresis (CZE). In the cat and the dog, CAE showed a single large oligoclonal-like peak, which occurred in the γ-region in the cat and the β-γ-region in the dog, whereas CZE showed a biclonal gammopathy with 2 very close narrow spikes in the γ- and β-γ-regions in the cat and dog, respectively. In selected cases, CZE may be more effective than routine CAE in distinguishing oligoclonal from monoclonal or biclonal paraproteinemia.     

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.)     

A case of atypical canine lymphoma with oral mass and multiple osteolysis

An 8-year-old female Golden Retriever had an oral mass and lameness. Multiple osteolysis of the systemic skeleton without monoclonal gammopathy was shown on electrophoresis of serum and urine samples. Cytological and histopathological examinations of the oral mass revealed atypical polymorphic cells similar to myeloid cells, and bone marrow aspiration indicated that these abnormal cells also might have invaded the bone marrow. These cells were negative to peroxidase and non-specific esterase staining, and clonal expansion of B lymphocytes could be detected by polymerase chain reaction (PCR) assay for antigen receptor gene rearrangement. The case was diagnosed as atypical lymphoma and treated by multi-drug chemotherapy. On the 142nd day after the first admission, the case had remission and the oral mass and multiple osteolysis were improved.     

Prognostic factors for multiple myeloma in the dog

Multiple myeloma was diagnosed in 60 dogs. Diagnosis was confirmed in each case by observation of greater than 5% plasma cells on examination of a bone marrow aspirate and detection of monoclonal gammopathy of immunoglobulin (Ig) A or IgG. Treatment with melphalan, cyclophosphamide, and prednisone was associated with long-term survival (median, 540 days). Response to therapy was significantly related to prognosis (P less than 0.01), whereas hypercalcemia and Ig light chain proteinuria (Bence Jones) were associated with shorter median survival times.     

Monoclonal Gammopathy in a Dog With Visceral Leishmaniasis

One dog with visceral leishmaniasis associated with monoclonal gammopathy is described. Most dogs with visceral leishmaniasis present with hyperproteinemia due to a polyclonal gammopathy, but the possibility of monoclonal gammopathy must be considered. Because dogs accompany their owners when they travel, the diagnosis of leishmaniasis should be considered if an animal with monoclonal gammopathy has visited an area where the disease is endemic. The observation of Leishmania in the macrophages of a bone marrow, lymph node smear, or skin biopsy specimen is diagnostic.     

Monoclonal immunoglobulin G cryoglobulinemia and multiple myeloma in a domestic shorthair cat

A 13-year-old castrated domestic shorthair cat was examined because of fever, anorexia, and dermatologic lesions. Crusting, erythema, and well-demarcated purple discoloration of the foot pads and the tips of the pinnae, nose, and tail were seen. A white flocculent precipitate was detected in cooled serum. This precipitate dissolved upon rewarming, consistent with a cryoglobulin. Hypercalcemia, high alanine and aspartate aminotransferase activities, thrombocytopenia, and a monoclonal IgG gammopathy were found. Numerous hepatic nodules were detected by means of abdominal ultrasonography. Cytologic evaluation of fine-needle aspirates of the liver and spleen revealed numerous plasma cells, and evaluation of a bone marrow aspirate revealed plasmacytosis. A diagnosis of multiple myeloma and monoclonal IgG cryoglobulinemia was made, and the cat was euthanatized.     

Hemophagocytic syndrome in a cat with multiple myeloma

An 11‐year‐old, castrated male, Domestic Medium Hair cat was presented to the University of Florida Small Animal Hospital with a 2‐week history of upper respiratory infection and increased serum globulins, as reported by the referring veterinarian. Physical examination was unremarkable other than melanosis of the left iris, with no evidence of ocular, nasal, or respiratory disease. Laboratory abnormalities included moderate nonregenerative anemia, mild leukopenia, mild hyperfibrinogenemia, severe hyperglobulinemia, mild hypoalbuminemia, and hypocholesterolemia. Abdominal radiographs and ultrasonographic examination revealed mild splenomegaly with no other abnormalities. Thoracic radiographs revealed no abnormalities. Cytologic evaluation of fine‐needle aspirates from the spleen, liver, and bone marrow revealed numerous plasma cells and many vacuolated macrophages exhibiting marked phagocytosis of mature erythrocytes and platelets, occasionally metarubricytes and leukocytes, and rarely plasma cells. The cytologic interpretation was multiple myeloma and associated hemophagocytic syndrome (HPS). Serum protein electrophoresis revealed a monoclonal gammopathy, providing further evidence for a multiple myeloma. To the authors' knowledge, this is the first report of HPS secondary to neoplasia in a cat.