Case Report Progression of a solitary, malignant cutaneous plasma-cell tumour to multiple myeloma in a cat A. Radhakrishnan1, R. E. Risbon1, R. T. Patel1, B. Ruiz2 and C. A. Clifford3 1 Mathew J. Ryan Veterinary Hospital of the University of Pennsylvania, Philadelphia, PA, USA 2 Antech Diagnostics, Farmingdale, NY, USA 3 Red Bank Veterinary Hospital, Red Bank, NJ, USA Abstract 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 Keywords hyperproteinaemia, months later, the cat developed clinical evidence of multiple myeloma based on positive Bence monoclonal gammopathy, Jones proteinuria, monoclonal gammopathy and circulating atypical plasma cells. This case multiple myeloma, pancytopenia, represents an unusual presentation for this disease and documents progression of an plasmacytoma extramedullary plasmacytoma to multiple myeloma in the cat. Introduction naemia, although it also can occur with IgG or IgA Plasma-cell neoplasms are rare in companion ani- hypersecretion (Matus & Leifer, 1985; Dorfman & mals. They represent less than 1% of all tumours in Dimski, 1992). Clinical signs of hyperviscosity dogs and are even less common in cats (Weber & include coagulopathy, neurologic signs (dementia Tebeau, 1998). Diseases represented in this category and ataxia), dilated retinal vessels, retinal haemor- of neoplasia include multiple myeloma (MM), rhage or detachment, and cardiomyopathy immunoglobulin M (IgM) macroglobulinaemia (Dorfman & Dimski, 1992; Forrester et al., 1992). and solitary plasmacytoma (Vail, 2001). These con- Coagulopathy can result from the M-component ditions can result in an excess secretion of Igs interfering with the normal function of platelets or (paraproteins or M-component) which produce a clotting factors. Renal dysfunction is often asso- monoclonal spike via serum protein electrophoresis. ciated with MM and may be the result of damage MM is a systemic proliferation of neoplastic by Bence Jones proteins, tumour infiltration, Correspondence address: plasma cells from the bone marrow. Consequences hypercalcaemia, amyloidosis or decreased perfu- Dr Anant Radhakrishnan of the systemic disease include bone pathology sion (MacEwen & Hurvitz, 1977). Other clinical Mathew J. Ryan Veterinary (lysis), hyperviscosity syndrome, blood dyscra- manifestations of MM include polyuria or poly- Hospital of the University sias, cytopenias and organ failure (MacEwen & dipsia secondary to hypercalcaemia or renal fail- of Pennsylvania 3900 Delancey Street Hurvitz, 1977). M-component elevation may ure, spinal pain and pathologic fractures. A Philadelphia, lead to hyperviscosity syndrome, characterized by diagnosis of MM requires at least two of four PA 19104-6010, USA increased serum viscosity, blood sludging and criteria: (1) greater than 20% plasma cells in the Tel: þ1 215 898 3207 Fax: þ1 215 573 6050 poor oxygen delivery to tissues. Hyperviscosity bone marrow, (2) monoclonal gammopathy, (3) e-mail: [email protected] occurs more commonly with IgM macroglobuli- osteolytic lesions and (4) Ig light chains (Bence 36 ª 2004 Blackwell Publishing Ltd Feline multiple myeloma and plasmacytoma 37 Jones protein) in the urine (Drazner, 1982; Eastman, revealed four lobulated, soft-tissue masses that 1996; Weber & Tebeau, 1998; Bienzle et al., 2000). encompassed the tarsus circumferentially. Radio- In contrast to MM, plasmacytomas are solitary graphs of the affected extremity revealed no evi- tumours containing neoplastic plasma cells. In dence of osteolysis. Complete blood count (CBC) dogs, two types of plasmacytomas have been and serum chemistry results were unremarkable. described: extramedullary and solitary osseous Segmental resection was carried out to remove forms that originate from soft tissue and bone, two of the lateral masses. Histopathology revealed respectively. Extramedullary plasmacytomas are a poorly differentiated polymorphous blastic-type commonly cutaneous and typically benign, and malignant plasma-cell tumour that stained posi- surgical excision is often curative (Mandel & tively for amyloid. Serum protein electrophoresis, Esplin, 1994). Non-cutaneous extramedullary whole-body radiographs (thorax and abdomen) plasmacytomas tend to be more aggressive and and bone marrow aspiration were carried out to are commonly associated with gastrointestinal further investigate the extent of disease. Serum tract, and typically, there is metastasis to the protein electrophoresis revealed a mild elevation local lymph nodes (Brunnert et al., 1992; Trevor of alpha-2 globulin concentration (1.65 g dLÀ1, et al., 1993; Jackson et al., 1994). Systemic pro- reference interval 0.2–1.5), consistent with an gression to MM is not typical with extramedullary inflammatory process. Radiographs revealed no plasmacytomas (Vail, 2001). Osseous plasmacyto- evidence of osteolytic lesions. Cytologic examin- mas occur in long bones, vertebral bodies, the ation of a bone marrow aspirate was interpreted as zygomatic arch and ribs. In dogs, solitary osseous erythroid hypoplasia, with only rare macrophages plasmacytomas can progress to MM (MacEwen and plasma cells reported. et al., 1984). The patient was transferred to a referral centre 4 There is a paucity of information in the veter- months later for further staging to rule out inary literature regarding plasmacytoma and MM abdominal organ involvement in anticipation of in the cat (Carothers et al., 1989; Forrester et al., radiation therapy. CBC and serum chemistry 1992; Larsen & Carpenter, 1994; Mandel & Esplin, results again were unremarkable. Abdominal 1994; Eastman, 1996; Sheafor et al., 1996; Weber & ultrasonography revealed an enlarged medial iliac Tebeau, 1998; Zikes et al., 1998; Bienzle et al., lymph node. Fine-needle aspiration of the lymph 2000; Hickford et al., 2000). In the cat, MM carries node was consistent with metastatic plasma-cell a poor prognosis, particularly when compared tumour (Fig. 1). Based on the diagnosis of metastasis with plasmacytomas, which may respond to sur- from the original solitary plasmacytoma, the patient gery alone (Mandel & Esplin, 1994). Cats with was referred to the oncology service of the Veterin- MM do not typically develop osseous lesions nor ary Hospital of the University of Pennsylvania, do they commonly develop solitary osseous plas- approximately 6 months after the initial identifica- macytomas (Weber & Tebeau, 1998). Although case tion of the mass and 4 months after the initial reports exist documenting plasmacytoma with a workup for MM. monoclonal gammopathy (Carothers et al., 1989; At presentation, the owner reported no clinical Larsen & Carpenter, 1994; Mandel & Esplin, 1994), abnormalities, with the exception of the soft-tissue to the authors’ knowledge, progression of a solitary mass overlying the tarsus. Physical and ophthalmo- plasmacytoma to MM has not been reported in the scopic examinations were otherwise unremarkable. cat. This report describes a cat with a solitary extra- The cat’s body weight was 8.04 kg. Measurements of medullary plasmacytoma that progressed to MM. the mass were slightly greater than those taken 2 months earlier. A CBC indicated a normal leucocyte count (5.65 K mLÀ1, reference interval 4.0–18.7), Clinical report neutropenia (0.760 K mLÀ1, reference interval An 11-year-old intact male domestic shorthair cat 2.30–14.0), normocytic, normochromic anaemia was examined by the local veterinarian for a mass (hematocrit 27.5%, reference interval 31.7–48.0) around the left tarsus. Physical examination and thrombocytopenia (platelet count 55.1 K mLÀ1, ª 2004 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 2, 1, 36–42 38 A. Radhakrishnan et al. Figure 1. (A) Cytologic smear made from an ultrasound-guided fine-needle aspirate of an iliac lymph node from a cat. There are large round-to-ovoid neoplastic cells admixed with moderate numbers of small lymphocytes and abundant blood [Wright– Giemsa stain, bar ¼ 40 mm]. (B) Two neoplastic round cells with a slight paranuclear Golgi clearing. One is binucleated, whereas the second cell shows a cleaved nucleus [Wright–Giemsa stain, bar ¼ 5 mm] reference interval 175–500). Cytologic review of the spike was detected within gamma globulin fraction blood smear revealed 53% (2.99 K mLÀ1)ofthe (3.73 g dLÀ1, reference interval 0.5–1.90) on serum leucocytes to be atypical plasma cells (Fig. 2). protein electrophoresis. Ig quantification by radial Abnormalities on serum chemistry included hyper- immunodiffusion identified an IgA gammopathy proteinaemia (11.7 g dLÀ1, reference interval 6.0–8.6), (IgA concentration >2000 mg dLÀ1, reference inter- hyperglobulinaemia (8.4 g dLÀ1, reference interval val 102–582). Radiographs of the thorax and abdo- 2.2–6.2), hypernatraemia (162 mmol LÀ1, reference men revealed no evidence of osteolytic lesions. The interval 146–157) and elevated aspartate aminotrans- bone marrow aspirate was haemodiluted precluding ferase activity (59 U LÀ1, reference interval 1–37). definitive analysis, but 73% of the nucleated cells Bence Jones proteins were detected in the urine with (500 cell differential count) were atypical plasma classical heat precipitation methods. A monoclonal cells. Based upon the monoclonal gammopathy, Bence Jones proteinuria and atypical plasma cells in blood, a diagnosis of MM was made. There was no evidence of