Multiple myeloma

From Felipedia

Fig. 1. Photomicrograph of a vertebral body biopsy from cat No. 1 with multiple myeloma. The biopsy consists of loosely arranged round to oval cells with eccentric nuclei. HE. Bar = 25 µm.

Fig. 2. Fine needle aspiration smear from the spleen of cat No. 2 with multiple myeloma. The nucleated cells present amidst a hemorrhagic background are round with an eccentrically located nucleus and a faint Golgi zone. Wright's stain. Bar = 25 µm.

Multiple myeloma consists of a clonal proliferation of malignant plasma cells that usually produce an immunoglobulin. The tumour originates in the bone marrow and may involve other organs to varying degrees. Affected cats generally are hyperglobulinemic. Leakage of free light chains into the urine results in proteinuria. The homogenous nature of the secreted paraprotein produces a narrow peak on serum and urine electrophoretograms. Multiple myeloma has been reported to constitute approximately 8% of all canine hematopoietic neoplasms, but it appears to be a relatively rare tumour in cats. In small animals, the presence of at least two of four features has been described as requisite for a diagnosis of multiple myeloma: paraproteinemia, osteolytic lesions, more than 20% plasma cells in bone marrow biopsies, and Bence-Jones (light chain) proteinuria^[1][2].

Studies in human patients indicate that monoclonal gammopathies of undetermined significance may precede the development of overt multiple myeloma by years and may accompany degenerative or infectious diseases without evidence of neoplasia. Similarly, multiple myeloma-like production of monoclonal immunoglobulins has been reported in dogs lacking evidence of a neoplasm but afflicted with pyoderma, leishmaniasis, plasmacytic enteritis, or Ehrlichia infection^[3]. Furthermore, osteolytic lesions and bone marrow infiltration with abnormal plasma cells were noted in a dog without a monoclonal gammopathy. Thus, non-secretory variants of multiple myeloma and non-neoplastic conditions mimicking multiple myeloma may exist in animals^[4].

Classifying plasma cell proliferations in cats poses an even greater challenge. Solitary extramedullary tumours producing a cell-bound monotypic immunoglobulin or accompanied by a monoclonal gammopathy were classified as plasmacytomas. A different presentation of an extramedullary plasmacytoma manifested with production of excess light chains, amyloid deposition, and tumour involvement of visceral organs. Hepatic plasmacytoma or plasmacytoid lymphoma were diagnosed in cats with clonal immunoglobulin production and Bence-Jones proteinuria; however, these cats lacked osteolytic lesions. Osteolysis and intramedullary plasma cell proliferation in association with a polyclonal gammopathy were diagnosed as multiple myeloma. Finally, feline cases more typical of "classical" multiple myeloma were reported to have bone marrow proliferation of plasma cells, paraproteinemia, and, in some cases, osteolytic lesions. Thus, plasma cell proliferations in cats may range from non-secreting solitary tumours to widespread non-secreting extramedullary tumours to predominantly intramedullary myelomas that elaborate monoclonal proteins^[5].

Clinical signs

The clinical presentation of cats with multiple myeloma tends to be variable. Non-specific presenting causes are depression, chronic infections, renal disease, vomiting and diarrhoea, neurologic abnormalities, and bleeding diatheses.

Hypercalcaemia is a common non-specific finding, thought to result from tumour-induced production of osteoclast-activating factors such as interleukin (IL)-6 and IL-1ß by stromal and bone cells. Increased ionized calcium concentration suggests paraneoplastic hypercalcemia rather than renal disease as the cause. The renal disease commonly observed in cats with multiple myeloma may result from a combination of impaired tubular catabolism of excess light chains, glomerular Bence-Jones protein deposits, amyloid deposits, and hypercalcemia-related tubular unresponsiveness. Bleeding diatheses arising from the interaction of the paraprotein with platelets or coagulation factors have been reported in humans and cats. Finally, inadequate or abnormal production of immunoglobulins may immunocompromise some patients so that opportunistic infections may occur^[6].

Diagnosis

Diagnosis is based upon presenting clinical signs and blood tests. Histopathoogy of extramedullary tumour will assist int eh diagnosis.

Treatment

Alkylating therapy with melphalan is the recommended treatment for multiple myeloma in small animals; radio-responsiveness of the tumour has not been evaluated in animals. The longest survival time reported in a cat with multiple myeloma treated with chemotherapy was 16 months; more commonly, the animals are euthanized within 6 months of diagnosis. Feline tumours classified as plasmacytomas may be locally invasive or may metastasize and then have generally responded poorly to therapy^[7]

Too few detailed cases of feline multiple myeloma are reported to correlate prognosis with immunoglobulin isotype. Although IgA appears to be less commonly produced than IgG, the five published cases (including this report) with an IgA paraprotein had visceral involvement and survival times ranging from a few days to 6 months. Either immunoglobulin has been associated with clinical signs of hyperviscosity, including cardiac insufficiency, retinal haemorrhages, and neurologic signs. This phenomenon relates to the size of the paraprotein and the degree of hyperglobulinemia. Since IgA may assume a dimeric or multimeric form, it may be more frequently associated with hyperviscosity than IgG. The single cat reported with a plasmacytoid tumour and IgM paraprotein production had severe hyperviscosity consistent with the large size of the IgM molecule. In humans, specific biochemical features of the monoclonal protein further contribute to clinical manifestations. Monoclonal IgG with kappa light chains results in cryoprecipitates more frequently than with alpha light chains. In small animals, alpha chains comprise the majority of immunoglobulin light chains produced by B cell neoplasms, thus offering a plausible explanation for the infrequent occurrence of cryoglobulin-associated disorders. Although the clinical manifestations of multiple myeloma in humans are known to vary with the isotype subclass, the occurrence of this in animals is unknown^[8].

References

1. ↑ Bataille R, Harousseau JL (1993) Multiple myeloma. N Engl J Med 336:1657-1664
2. ↑ Breuer W, Colbatzky F, Platz S, Hermanns W (1993) Immunoglobulin-producing tumours in dogs and cats. J Comp Pathol 109:203-216
3. ↑ McDonald WJ, Burton SA, Fuentealba IC (1994) Plasma cell myeloma producing an immunoglobulin A paraprotein in a cat. Can Vet J 35:157
4. ↑ Forrester SD, Greco DS, Relford RL: Serum hyperviscosity syndrome associated with multiple myeloma in two cats. J Am Vet Med Assoc 200:79-82, 1992
5. ↑ Larsen AE, Carpenter JL (1994) Hepatic plasmacytoma and biclonal gammopathy in a cat. J Am Vet Med Assoc 205:708-710
6. ↑ Carothers MA, Johnson GC, DiBartola SP, Liepnicks L, Benson MD (1989) Extramedullary plasmacytoma and immunoglobulin-associated amyloidosis in a cat. J Am Vet Med Assoc 195:1593-1597
7. ↑ Hawkins EC, Feldman BF, Blanchard PC (1986) Immunoglobulin A myeloma in a cat with pleural effusion and serum hyperviscosity. J Am Vet Med Assoc 188:876-878
8. ↑ Drazner FH (1982) Multiple myeloma in the cat. Comp Contin Educ 4:206-216