Plasma cell neoplasms originate from terminally differentiated B lymphocytes that have undergone malignant transformation.
These neoplasms incorporate a wide range of clinical syndromes including multiple myeloma, macroglobulinemia, solitary osseous
plasmacytoma, and extramedullary plasmacytoma. In this article, we focus on multiple myeloma, which refers to diffuse disease
and, clinically, is the most important plasma cell neoplasm. See the next article in this issue for a discussion of plasmacytomas,
which involve soft tissue or bone.
SIGNALMENT AND CAUSE
Multiple myeloma is an uncommon lymphoproliferative disease in animals, accounting for less than 8% of all hematopoietic tumors
in dogs. No breed or sex predilections exist, and older dogs are most commonly affected, with a mean age of 8 to 9 years.1-3 Multiple myeloma is even less common in cats, with a median age of 12 to 14 years and possible male predisposition.2,4-7
The cause of multiple myeloma in companion animals is largely unknown. In people, plasma cell diseases are associated with
working in the agricultural industry, exposure to petroleum products, and chronic exposure to an antigen stimulus.8-11 At a molecular level, multiple myeloma has been associated with altered expression of the c-myc oncogene (people) and the
cell cycle protein cyclin D (people and dogs).12-14 One case report involving feline siblings with multiple myeloma suggests that a genetic predisposition may exist.5 In contrast to other hematopoietic diseases such as lymphoma, there is no evidence that feline immunodeficiency virus, feline
leukemia virus, or feline infectious peritonitis virus infections are related to multiple myeloma development in cats.7
Multiple myeloma is a B cell malignancy characterized by the infiltration and growth of plasma cells in the bone marrow (Figure 1). Normal B cells are transformed into malignant plasma cells in a multistep process that includes cumulative mutational damage
and multiple genetic abnormalities. Myeloma cells are clonal expansions of a neoplastic plasma cell, and they produce an identical
immunoglobulin protein, called the paraprotein or monoclonal (M) protein, in large quantities. These paraproteins can often be identified as a monoclonal spike on a serum or urine protein electrophoretogram;
protein electrophoresis is performed at many commercial laboratories (e.g. Colorado State University's College of Veterinary Medicine & Biomedical Sciences Veterinary Diagnostic Laboratories, Texas
A&M University's Texas Veterinary Medical Diagnostic Laboratory).
Figure 1. A photomicrograph of a bone marrow aspirate from a dog with multiple myeloma. Plasma cells (black arrows) are characterized
by an eccentric nucleus, basophilic cytoplasm, and perinuclear clear zone/Golgi. Mitotic figures are present (white arrow)
(Wright's stain; 500X).
The paraprotein may represent a complete immunoglobulin or a portion of the immunoglobulin (light or heavy chain). Immunoglobulin
G (IgG) and immunoglobulin A (IgA) gammopathies are the most common in people, dogs, and cats; immunoglobulin M (IgM) gammopathy
(macroglobulinemia) is rare. While IgG and IgA gammopathies are equally common in dogs, cats are reported to develop 80% IgG
and 20% IgA gammopathies.1,4 Biclonal gammopathies, occasionally reported in veterinary patients, may be attributable to the development of two independent
neoplastic clones, isotype switching of some clones, or spurious electrophoretic biclonal peaks due to splitting of dimeric
or multimeric paraproteins (e.g. IgA).4,7,15 Pure light chain (kappa or lambda type) production, referred to as light chain myeloma or Bence Jones myeloma, has rarely been reported in cats and dogs.3,16