Progression of cutaneous plasmacytoma to plasma cell leukemia in a dog

A 5‐year‐old male neutered Bernese Mountain Dog was presented for cutaneous plasmacytoma, which was treated by surgical excision. Four months later, the dog developed multiple skin masses, hyphema, pericardial and mild bicavitary effusions, myocardial masses, and marked plasmacytosis in the peripheral blood. Circulating plasma cells expressed CD34 and MHC class II by flow cytometry. Immunocytochemistry demonstrated that these cells were strongly positive for multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM‐1) and weakly to moderately positive for Pax5. The dog was hypoglobulinemic but had a monoclonal IgA gammopathy detected by serum immunofixation electrophoresis. The PCR analysis of antigen receptor gene rearrangements (PARR) by fragment analysis using GeneScan methodology revealed that plasmacytoid cells in the original cutaneous plasmacytoma and peripheral blood had an identical immunoglobulin heavy chain gene (IgH) rearrangement, indicating that both populations were derived from the same neoplastic clone. Canine cutaneous plasmacytoma rarely progresses to a malignant form and plasma cell leukemia is rarely diagnosed in the dog. This report describes a case of cutaneous plasmacytoma progressing to plasma cell leukemia with a rapid and aggressive clinical course. This report also highlights the utility of flow cytometry, immunocytochemistry, immunofixation electrophoresis, and PARR by fragment analysis using GeneScan methodology in the diagnosis of this hematopoietic neoplasm.     

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 protein electrophoresis in 147 dogs

Reference intervals for serum protein electrophoresis (SPE) were created from a group of 75 clinically healthy dogs and compared with SPE results obtained from clinical cases presented to the University of Bristol over an eight-and-a-half-year period. A total of 147 dogs, in which SPE had been performed, had complete case records available and thus met the inclusion criteria. Signalment and final diagnoses taken from the case records and SPE results were divided into normal and abnormal based on the newly established reference intervals. Cases were grouped according to the SPE protein fraction abnormalities and diagnosis using the DAMNITV classification system. Of the 147 cases, 140 (95.2 per cent) had abnormal SPE results. The most common protein fraction abnormality was decreased albumin (59.3 per cent) followed by a polyclonal increase in γ globulins (38.6 per cent). Decreased β-1 globulins and increased β-2 globulins were documented in 36.4 and 30.0 per cent of cases, respectively. The most common DAMNITV classification associated with abnormal SPE results was infectious/inflammatory disease, which was diagnosed in 79 of 140 cases (56.4 per cent). Monoclonal gammopathies were noted in eight dogs (5.7 per cent), and underlying lymphoproliferative disease was present in all cases where a diagnosis was achieved, including multiple myeloma (four dogs), splenic plasmacytoma (one dog), hepatic plasmacytoma (one dog) and lymphoma (one dog).     

Monoclonal Gammopathy in a Dog With Chronic Pyoderma

A monoclonal gammopathy composed of immunoglobulin G, with concurrent light-chain proteinuria and generalized lymph node plasmacytosis, was associated with chronic pyoderma in a dog. A uniform population of plasma cells was observed cytologically and histologically in multiple lymph node specimens. A diagnosis of monoclonal gammopathy of unknown significance was eventually made by exclusion of other known causes of monoclonal gammopathy, resolution after antibiotic therapy, and no evidence of lymphoproliferative disease after 11 months of follow-up and subsequent necropsy. This report expands the diagnostic considerations for monoclonal gammopathies in the dog.     

Histopathologic and immunophenotypic characterization of extramedullary plasmacytomas in nine cats

To contribute to the existing body of knowledge in the literature on the apparently rare extramedullary plasmacytoma in cats, lymphoid tumors with plasmacytic cellular morphology taken from nine cats were examined. The paraffin-embedded material was investigated by standard hematoxylin and eosin, and special staining techniques (Giemsa, Congo-red, and periodic acid-Schiff reaction). The tumors also were examined immunohistochemically for the presence of immunoglobulin G, immunoglobulin A, immunoglobulin M, immunoglobulin light chains (lambda, kappa), various amyloid proteins, and FeLV-antigen (p27 protein). An immunoglobulin-producing tumor of plasmacellular origin (extramedullary plasmacytoma [EMP]) could be diagnosed in all cases on the basis of immunohistochemical light-chain expression. All but one of the neoplasms occurred in the skin of older, predominantly male cats. As in humans and dogs, the following types could be identified according to their morphologic features: mature type (two), cleaved type (two), asynchronous type (four), and polymorphous type (one). The tumor tissue of three cats revealed amyloid deposits, which were immunohistochemically diagnosed as ALlambda-amyloid in all three cases.     

Vertebral plasma cell tumors in 8 dogs

The case histories of 8 dogs with spinal pain and neurologic deficits associated with vertebral plasma cell tumor are reviewed. Four dogs had solitary plasmacytoma, 3 had multiple myeloma, and 1 dog had 2 vertebral lesions with no evidence of disseminated disease. Four dogs were treated: 2 with multiple myeloma received chemotherapy only and survived 17 and 26 months, respectively. Two dogs with solitary plasmacytomas of the spine had chemotherapy and radiotherapy: the 1st survived 4 months and was euthanized after developing radiation myelopathy; the 2nd survived 65 months before developing multiple myeloma. The diagnosis of solitary plasmacytoma of the spine versus multiple myeloma is discussed.     

Protein characterization using electrophoresis and immunofixation; a case‐based review of dogs and cats

Protein electrophoresis and immunotyping can be a useful adjunct to the standard biochemical techniques for characterizing serum and urine proteins. This paper reviews currently available and commonly used methods for diagnostic protein electrophoresis, including both agarose gel and capillary zone electrophoretic techniques and total protein assessments. Immunofixation and immunosubtraction methods for identification of immunoglobulin location and class are also presented. Practical application of quality assurance and quality control strategies in compliance with American Society of Veterinary Clinical Pathology (ASVCP) best practices are discussed. Commonly encountered serum and urine electrophoretic diagnostic patterns, including electrophoretically normal, acute‐phase protein responses, polyclonal gammopathies, restricted polyclonal/oligoclonal gammopathies, paraproteinemias (monoclonal or biclonal gammopathies), and Bence‐Jones proteinurias are also reviewed using relevant case material. Cases in which immunofixation electrophoresis are particularly useful are highlighted, and methodologies to more accurately quantify serum monoclonal proteins (M‐proteins), monitoring tests commonly used in human medicine, are discussed.     

Multiple myeloma in cats: variable presentation with different immunoglobulin isotypes in two cats

Multiple myeloma was diagnosed in two cats with monoclonal hyperglobulinemia, proteinuria, and plasma cell proliferations in bone marrow. An immunoglobulin G-producing myeloma occurred in the vertebral bone marrow of one cat, and twice responded to surgical reduction followed by a combination of local irradiation and chemotherapy. The cat's survival time was approximately 2 years. The other myeloma in a cat that presented with hypercalcemia and renal insufficiency involved visceral organs and produced a biclonal peak due to immunoglobulin A dimer formation on serum electrophoresis. This cat's tumor did not respond to chemotherapy.     

Immunoglobulin A monoclonal gammopathy in two horses with multiple myeloma

The clinical findings in two horses with secretory multiple myeloma and secondary immunoglobulin A (IgA) monoclonal gammopathy were non-specific and included weight loss, pale mucous membranes, limb oedema and bacterial respiratory tract infection. Consistent laboratory abnormalities included hyperproteinaemia, hyperglobulinaemia, hypoalbuminaemia and hypercalcaemia. The diagnosis was based on the presence of IgA monoclonal gammopathy in serum and urine and bone marrow plasmacytosis (> 10 per cent). One horse was euthanased; it had neoplastic plasma cell infiltrates in its kidneys, spleen, liver, bone marrow, myocardium and adrenal glands. The other horse was treated for a bacterial pneumonia and was still alive six months after it was first examined.     

Intraocular extramedullary plasmacytoma in a cat

An 8-year-old, castrated male Domestic Short-haired cat was referred for evaluation of a possible intraocular neoplasm following previous ocular trauma. The eye was blind, and uveitis and an iridal mass were noted on examination. An enucleation was performed and the mandibular lymph node excised. Histopathologic examination revealed neoplastic proliferation of plasma cells in the iris and lymph node. No other evidence of disseminated disease was detected. This is the first case reported of an intraocular extramedullary plasmacytoma in the cat. The variation in clinical manifestations and potential association with multiple myeloma are not known at this time. Disseminated metastasis from a primary plasmacytoma of the uveal tract could also involve the bone marrow and be indistinguishable from multiple myeloma. Early enucleation, as in trauma-associated sarcomas, may be indicated to prevent metastasis. Periodic systemic evaluation for evidence of multiple myeloma should be performed.     

Clinico-pathological aspects of canine cutaneous and mucocutaneous plasmacytomas

In this study the clinico-pathological aspects of cutaneous and mucocutaneous plasmacytomas were investigated in 63 dogs (one dog with two tumours). The tumours were most commonly observed in the skin of the trunk and legs. Yorkshire Terrier (n = 8) was the most commonly affected breed and males were affected more commonly than females (36 versus 23, respectively). Plasmacytomas were histologically classified into mature, hyaline, cleaved, asynchronous, monomorphous blastic and polymorphous blastic cell types. Monomorphous blastic cell type was the most frequent type (n = 21), followed by cleaved (n = 19) and asynchronous (n = 11) cell types. Secondary amyloid depositions were observed in eight cases. Immunohistochemical staining showed monoclonal lambda light chain positivity in all cases. In the immunohistochemical staining for cyclin D1, which is a prognostic marker in human plasma cell tumours, moderate numbers of positive tumour cells were observed in only one case of (muco)cutaneous plasmacytoma. All other cases were negative or contained few positive tumour cells. On the other hand, high numbers of tumorous plasma cells reacted positively with cyclin D1 in three out of six cases of canine multiple myelomas. Prognosis of the (muco)cutaneous plasmacytomas was good, except in one dog which developed a lymphoma afterwards. No significant correlations were observed between the cell type and the location of the tumour, presence of amyloid or prognosis.     

Multiple myeloma in 16 cats: a retrospective study

BACKGROUND: There is limited published information regarding feline multiple myeloma. Diagnostic criteria are derived from canine studies and to our knowledge, have not been critically reviewed for cats. OBJECTIVE: To evaluate the clinical and laboratory findings in cats with multiple myeloma and appraise diagnostic criteria. METHODS: Retrospective evaluation of medical records was performed. Inclusion required an antemortem diagnosis of multiple myeloma using 2 of 4 criteria: 1) >or=20% plasma cells in the bone marrow, or >or=10% if atypical plasma cells; 2) paraproteinemia; 3) radiographically-evident osteolysis; 4) light chain proteinuria. Alternatively, a postmortem diagnosis was based on the findings of multiple plasma cell neoplasms, with marrow involvement. RESULTS: Sixteen cats were diagnosed with multiple myeloma between 1996 and 2004, with a median age of 14.0 years; 9 of 16 (56%) were castrated males, and 7 of 16 (44%) were spayed females. Laboratory abnormalities included hyperglobulinemia (14/16, 87.5%), with 11/14 (78.5%) monoclonal and 3/14 (21.4%) biclonal gammopathies; hypoalbuminemia (4/16, 25%); light chain proteinuria, (4/9, 44.4%); hypocholesterolemia (11/16, 68.7%); hypercalcemia, (3/15, 20%); nonregenerative anemia, (11/16, 68.7%); regenerative anemia, (1/16, 6.2%); neutropenia (5/15, 33.3%); thrombocytopenia (8/16, 50%); and marrow plasmacytosis (14/15, 93.3%). Plasma cells were markedly immature, atypical, or both in 10 of 12 (83.3%) cats. Focal or multifocal osteolysis was noted in 6 of 12 (50%) cats for which radiographs were available for review; generalized osteopenia was found in 1 (8.3%) cat. Noncutaneous, extramedullary tumors were found in all cats assessed, 7/7 (100%), including spleen (6), liver (3), and lymph nodes (4). The disease in 1 of 2 cats with cutaneous tumors progressed to plasmacytic leukemia. CONCLUSIONS: Common findings in feline multiple myeloma include atypical plasma cell morphology, hypocholesterolemia, anemia, bone lesions, and multi-organ involvement. Based on the results of this study, we advocate modifying diagnostic criteria in cats to include consideration of plasma cell morphology and visceral organ infiltration.     

Cutaneous plasmacytomas with amyloid in six dogs.

Cutaneous plasmacytomas associated with local deposition of amyloid were diagnosed by light microscopy in a series of six older dogs (mean age 10.7 years) consisting of two Cocker Spaniels, a Poodle, a Weimeraner, and two mixed-breed dogs. The neoplasms occurred on the digits (2 dogs), forelimb (2 dogs), lip (1 dog), and ear (1 dog). In most cases, groups of neoplastic plasma cells were widely separated by large homogeneous islands of amyloid. The neoplastic cells had characteristic plasmacytoid features, but the degree of pleomorphism varied greatly between different neoplasms. In four of the six tumors, the diagnosis of plasmacytoma was confirmed by the demonstration of a monoclonal plasma cell population using immunofluorescent staining for anti-canine immunoglobulins. In these tumors, the neoplastic cells reacted with only one class of immunoglobulins (IgG). The amyloid did not react with any of the reagents used. The suspicion that the amyloid was of immunoglobulin origin (primary amyloid) was supported by its retention of birefringence under polarized light after treatment with potassium permanganate and staining with Congo red.     

Bovine-murine hybridoma that secretes bovine monoclonal antibody of defined specificity

Spleen cells from a calf hyperimmunized with bovine enteric coronavirus were fused with nonproducer mouse plasmacytoma cells. Stable hybridoma lines secreting bovine immunoglobulins were obtained. One line secreted monoclonal bovine immunoglobulin G2, which reacted specifically with bovine enteric coronavirus in an enzyme-linked immunosorbent assay, inhibited virus hemagglutination, and precipitated a structural polypeptide with a molecular weight of 26,000 daltons.     

A porcine-murine hybridoma that secretes porcine monoclonal antibody of defined specificity

Spleen cells from a pig hyperimmunized with Escherichia coli were fused with nonproducer mouse plasmacytoma cells. Stable hybridoma lines secreting porcine immunoglobulins were obtained. One line secreted monoclonal porcine immunoglobulin G, which reacted specifically with E coli in an enzyme-linked immunosorbent assay and precipitated a polypeptide of molecular weight of 50,000. This is the first report of a stable porcine-murine hybridoma producing porcine antibody of defined specificity.     

Neurologic complications of IgA multiple myeloma associated with cryoglobulinemia in a dog

A diagnosis of vertebral multiple myeloma, based on radiographic evidence of osteolytic lesions and the finding of monoclonal paraprotein and large numbers of plasma cells in bone marrow biopsies, was made in a mature Doberman Pinscher. The abnormal serum paraprotein was a cryoglobulin of the immunoglobulin A class. Neurologic signs associated with the tumor included pain, progressive pelvic limb paresis, and paraplegia that developed during a 6-week period.     

Rat immunoglobulins

Five immunoglobulin isotypes (or classes) have been identified in the human as well as in the rat species. The homologies between the human and the rat immunoglobulin classes have been well defined with the help of the monoclonal immunoglobulins produced by the LOU immunocytomas (plasmocytomas,myeloma tumours). The LOU rat immunocytomas model, the physicochemical and the biological properties of the rat immunoglobulins are described in this review.     

Renal extramedullary plasmacytoma in a dog

A 10-year-old, intact male Siberian husky dog was presented for a suspected left renal cyst. Computed tomography (CT) identified a large, left kidney mass with retroperitoneal hemorrhage. A left-sided nephrectomy was performed, and histopathology confirmed a renal plasmacytoma. Perioperative screening for multiple myeloma was negative. The dog was lost to follow-up and was euthanized 11 months after surgery. A necropsy was not performed. To the authors’ knowledge, this is the first case of renal extramedullary plasmacytoma in a dog.Key clinical message:This report describes the clinical presentation, and laboratory, diagnostic imaging, and surgery findings of a case of renal extramedullary plasmacytoma in a dog.     

Cyclical 10-day dosing of melphalan for canine multiple myeloma

Canine multiple myeloma (MM) is typically treated with melphalan chemotherapy. A protocol with repeated 10-day cyclical dosing of melphalan has been used at our institution but has not been described in the literature. Our objectives were to describe the outcome and adverse events of this protocol in a retrospective case series. We hypothesised the cyclical 10-day protocol would have similar outcomes compared to other reported chemotherapy protocols. Dogs diagnosed with MM that received melphalan treatment at Cornell University Hospital for Animals were identified through a database search. Records were retrospectively reviewed. Seventeen dogs met inclusion criteria. Lethargy was the most common presenting complaint. The median duration of clinical signs was 53 days (range, 2–150 days). Seventeen dogs had hyperglobulinemia with 16/17 having monoclonal gammopathies. Sixteen dogs had bone marrow aspiration and cytology performed at initial diagnosis and plasmacytosis was diagnosed in all. Based on serum globulin concentrations, 10 of 17 dogs (59%) achieved complete response (CR), and 3 dogs (18%) achieved partial response (PR), for an overall response rate of 76%. The median overall survival time was 512 days (range, 39–1065). Retinal detachment (n = 3) and maximum response of CR/PR (n = 13) were associated with overall survival on multivariate analysis (p = .045 and .046, respectively). Adverse events were minimal with diarrhoea being the most reported (n = 6). This cyclical 10-day protocol was better-tolerated with fewer adverse events than with other reported chemotherapy protocols, but response rate was also lower, likely due to a lower dosing intensity.     

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.