Presumptive increase in protein‐bound serum calcium in a dog with multiple myeloma

Abstract: An 11‐year‐old male castrated Australian Shepherd was presented with a history of lethargy, panting, and weight loss for 1 month. Physical examination revealed a moderately enlarged spleen. Laboratory abnormalities included thrombocytopenia and marked hypercalcemia, with hyperglobulinemia, hypoalbuminemia, and a monoclonal spike in the β‐globulin region on serum protein electrophoresis. Serum total calcium concentration was markedly increased (16.5 mg/dL, reference interval 8.9–11.4 mg/dL) but ionized calcium concentration (1.39 mmol/L) was within the reference interval (1.25–1.45 mmol/L). Isosthenuria was noted, but the dog was not polyuric or polydipsic. Serum parathyroid hormone concentration was within reference limits and parathyroid hormone‐related peptide concentration was 0 pmol/L. Radiographic findings were largely unremarkable. Results of cytologic evaluation of a fine‐needle aspirate specimen from the spleen indicated plasma cell neoplasia. Based on the results of the electrophoresis, splenic aspirates, radiographs, and hypercalcemia, a diagnosis of splenic multiple myeloma was made. The marked hypercalcemia, normal ionized calcium and parathyroid hormone concentrations, and lack of osteolytic lesions indicated a presumptive increase in protein‐bound serum calcium, likely due to binding to molecules of the paraprotein (M protein). Protein binding of calcium in dogs with multiple myeloma should be considered as a potential mechanism of elevated total serum calcium concentration.     

Erythrophagocytic multiple myeloma in a cat

A 7-year-old neutered male domestic shorthair cat was presented to the Veterinary Medical Teaching Hospital at the University of Georgia for further evaluation of a suspected osteolytic lesion of the left 10th rib. Results of a CBC and biochemistry profile revealed mild nonregenerative anemia, hyperproteinemia, hyperglobulinemia, and hypercalcemia. Serum protein electrophoresis was consistent with a monoclonal gammopathy. Marked proteinuria with an increased urine protein to creatinine ratio was found. Cytologic examination of the liver, spleen, and bone marrow revealed numerous plasma cells, many of which were erythrophagocytic. Within the bone marrow, the plasma cells contained phagocytosed metarubricytes in addition to phagocytosed erythrocytes. A diagnosis of erythrophagocytic multiple myeloma was made and treatment with prednisone and melphalan was begun. Four weeks after presentation, the cat was euthanized due to clinical deterioration. A complete necropsy was performed. The distal one-third of the left 10th rib was completely absent. Histologically, there was no evidence for osteolysis or neoplastic cells in the remaining portion of the rib. However, large sheets of plasma cells were found infiltrating the spleen and bone marrow. Moderate erythrophagocytosis by the plasma cells was observed in both organs. The plasma cells, including the erythrophagocytic cells, were positive for CD79alpha by immunohistochemical staining. Erythrophagocytosis by plasma cells as a cause of anemia is uncommon in people with multiple myeloma and is rare in animals. To our knowledge, this is the first report of erythrophagocytic plasma cells in a cat with multiple myeloma.     

Light-chain multiple myeloma in a cat.

A diagnosis of light-chain multiple myeloma was made in an 11-year-old male American Shorthair cat. The cat showed atypical plasma cell infiltration in the bone marrow, biclonal gammopathy caused by polymerization of myeloma protein (M-protein), and Bence-Jones proteinuria. The M-protein in the serum of the cat was analyzed by using 12% sodium dodeyl sulfate (SDS) polyacrylamide gel electrophoresis with Coomassie brilliant blue staining. An intense band with a size of 27 kDa, the size of the immunoglobulin light chain, was clearly observed, whereas the band corresponding to the immunoglobulin heavy chain (59 kDa) was undetectable. The 27-kDa band was confirmed to be an immunoglobulin light chain by Western blotting by using antibodies for feline immunoglobulin. These data suggested that the neoplastic plasma cells produce light chain only, leading to the diagnosis of light-chain multiple myeloma in the cat.     

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.     

Characterization of a homogeneous paraprotein from a horse with spontaneous multiple myeloma syndrome

A novel myeloma paraprotein has been isolated from a horse with a lymphoid tumor. The protein was a euglobulin and consequently was readily isolated from serum in pure form and high yield by simple dilution in distilled water. The purified intact protein had a molecular weight of 150,000 and was composed of heavy and light chains, both of which had blocked amino-termini and were thus not susceptible to amino-terminal sequence analysis. The amino acid compositions of these respective chains corresponded to those of comparable chains from immunoglobulins of other species. Peptide maps of paraprotein light chains prepared by high pressure liquid chromatography corresponded in part to those of normal pooled equine light chains. The identification of this paraprotein as an equine AI (aggregating immunoglobulin) protein was confirmed by serological analysis using a specific antiserum. The relationship of this particular protein to other members of the immunoglobulin family was further demonstrated by the production of an anti-idiotypic antiserum individually specific for this molecule.     

Progression of a solitary, malignant cutaneous plasma-cell tumour to multiple myeloma in a cat

An 11‐year‐old male domestic shorthair cat was examined because of a soft‐tissue mass on the left tarsus previously diagnosed as a malignant extramedullary plasmacytoma. Findings of further diagnostic tests carried out to evaluate the patient for multiple myeloma were negative. Five months later, the cat developed clinical evidence of multiple myeloma based on positive Bence Jones proteinuria, monoclonal gammopathy and circulating atypical plasma cells. This case represents an unusual presentation for this disease and documents progression of an extramedullary plasmacytoma to multiple myeloma in the cat.     

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.     

Multiple myeloma with central nervous system involvement in a cat

CASE DESCRIPTION: A 1.5-year-old spayed female domestic shorthair cat was admitted for hind limb locomotor difficulties and signs of pain along the lumbar portion of the vertebral column. At the time of referral, the cat was paraparetic with deficits in the spinal reflexes of the hind limbs. Neuroanatomic localization was at the L6-S2 spinal cord segments, corresponding approximately to the region of the L4-L6 vertebral bodies. CLINICAL FINDINGS: Radiography revealed a mixed osteolytic-proliferative lesion within the body of L5 involving the cranial end plate, as well as punctate radiolucencies in the distal portion of the femur. Magnetic resonance imaging revealed an intramedullary spinal cord lesion along with extensive meningeal and nerve root lesions in the area of the L4-L6 vertebral bodies. Cytologic analysis of a bone marrow aspirate from the right trochanteric fossa revealed a substantial plasma cell infiltrate. Analysis of CSF revealed a high protein concentration and morphologically abnormal plasma cells. Urine, but not serum, protein electrophoresis revealed a sharp gamma-globulin peak consistent with a monoclonal band of Bence-Jones proteins. The diagnosis was multiple myeloma. TREATMENT AND OUTCOME: The cat was treated with melphalan and prednisolone. A rapid clinical response was reported, and by week 3 after diagnosis, the cat's locomotion and behavior had normalized. However, by month 4, multifocal neurologic deficits were evident. The cat was euthanized at 9 months because of tetraparesis and substantial weight loss. CLINICAL RELEVANCE: To our knowledge, this is the first report of myeloma in a cat that had electrophoretically detectable light chain proteinuria but lacked a detectable serum monoclonal gammopathy.     

Intraocular melanoma with multiple metastases in a cat

An 11-year-old cat with an intraocular melanoma was treated for 2 years for the secondary effects of the tumor (glaucoma, exposure keratitis) before enucleation was required. One year after enucleation, the cat was examined because of labored breathing. The cat was thin, appeared depressed, and had signs of respiratory compromise secondary to pleural effusion. Treatment was not instituted, and the cat was euthanatized. Metastasis of the primary melanoma to the lungs, pericardium, parietal pleura, mediastinum, hilar lymph nodes, diaphragm, liver, and omentum was confirmed at necropsy. Intraocular melanomas in the cat have been implicated to have a greater malignant potential than those in the dog; however, few cases have been reported with long-term follow-up information.     

IgA multiple myeloma in a dog

Multiple myeloma was diagnosed in a 10-year-old female Labrador which showed signs of weight loss, lethargy and skeletal pain. Radiography revealed well circumscribed osteolytic lesions in vertebrae, sternebrae, and the left humerus and radius along with generalised osteoporosis. The number of plasma cells in the bone marrow was increased and the serum gamma globulin concentration was elevated. Treatment with cyclophosphamide, mephalan and prednisone successfully controlled the malignancy but also resulted in suppression of the bone marrow. There was a remission time of 21.5 months.     

IgA multiple myeloma in a dog

Multiple myeloma was diagnosed in a lo-year-old female Labrador which showed signs of weight loss, lethargy and skeletal pain. Radiography revealed well circumscribed osteolytic lesions in vertebrae, sternebrae, and the left humerus and radius along with generalised osteoporosis. The number of plasma cells in the bone marrow was increased and the serum gamma globulin concentration was elevated. Treatment with cyclophosphamide, mephalan and prednisone successfully controlled the malignancy but also resulted in suppression of the bone marrow. There was a remission time of 21.5 months.     

Calcinosis involving multiple paws in a cat with chronic renal failure and in a cat with hyperthyroidism

Calcinosis of multiple paws is described in two cats. A metastatic pathogenesis was supported by the laboratory findings of hyperphosphataemia and a calcium x phosphorus solubility product > 7 g/L. Hyperparathyroidism could not be confirmed because a valid feline parathyroid hormone assay was not available at the time. One cat was diagnosed with chronic renal failure and presented initially with an irregular nodular calcification on the chin. Dietary and medical management was unsuccessful and ultimately the animal was euthanased. Hyperthyroidism was diagnosed in another cat by laboratory findings and scintigraphic imaging. In addition, the cat had a hyperphosphataemia in the absence of azotaemia. Intravenous administration of radioactive iodine as (131)I was accompanied by reduction and normalization in serum total thyroxine and phosphorus concentrations and resulted in resolution of calcification in the paws.     

Immunoglobulin A myeloma in a cat with pleural effusion and serum hyperviscosity

Immunoglobulin A myeloma, serum hyperviscosity, and septic pleuritis were diagnosed in a cat with pleural and peritoneal effusions. Serum hyperviscosity was determined by use of a WBC pipette, and clinical manifestations included retinopathy and cardiac changes. The presence of Salmonella typhimurium in the pleural fluid may have resulted from increased susceptibility to infection. Postmortem examination revealed plasma cell infiltration of the pleura, mesenteric lymph nodes, and the serosa of the intestine, liver, and spleen. This case represents an unusual form of myeloma in the cat.     

Refeeding syndrome in a cat with hepatic lipidosis

Refeeding syndrome is characterized by severe hypophosphatemia occurring in patients given enteral or parenteral nutrition after severe weight loss. There are few veterinary reports that describe this syndrome but it is well documented in human medicine. This report describes a case of a domestic shorthair cat diagnosed with hepatic lipidosis following a 4-week history of decreased appetite and weight loss and in whom refeeding syndrome was documented after initiation of enteral nutrition. Clinical findings, blood work abnormalities and disease progression in this patient are described from the time of diagnosis through to recovery. A review of the current literature pertinent to this clinical syndrome is included.     

Zollinger-Ellison syndrome in a cat

Zollinger-Ellison Syndrome in a 12-year old castrated male European Shorthair cat is described. The clinical symptoms were vomiting, weight loss, listlessness and alternating diarrhoea and obstipation. An endocrine tumour near the pancreatic duct had metastasised to the liver. Many duodenal ulcers were present. Immunohistochemistry revealed cells positive for gastrin and neuron-specific enolase (NSE) scattered throughout the tumour.     

Systemic AL amyloidosis associated with multiple myeloma in a horse

AL amyloidosis is the most common type of systemic amyloidosis in humans, and it is frequently associated with multiple myeloma. But, AL amyloidosis is very rare in domestic animals. A 16-year-old Quarter horse gelding was diagnosed with systemic AL amyloidosis associated with multiple myeloma. Clinical problems were rapid weight loss, muscle atrophy, soft unformed stool, and ventral edema. Grossly, diffuse gastrointestinal hemorrhage, markedly thickened jejunal mucosa, and splenomegaly were present. Microscopically, diffuse severe amyloid deposits were present in the lamina propria of glandular stomach, duodenum, and jejunum. Much of the spleen and sternal bone marrow was replaced by neoplastic round cells, and multiple foci of amyloid were also present in the spleen and bone marrow. Electron microscopy revealed the neoplastic round cells to be of plasma cell origin, and the amyloid showed a strongly positive immunoreactivity with polyclonal anti-human immunoglobin lambda light-chain antisera. To our knowledge, this is the second report describing systemic AL amyloidosis in domestic animals-associated plasma cell neoplasia and the first associated with multiple myeloma, as is common in humans.