Multiple myeloma is a tumor of plasma cell origin that localizes to the bone marrow of the axial skeleton causing bone lysis, pathologic fractures, and spinal cord compression. Myelomas appear most frequently as polyostotic aggressive bone lesions in the spine and pelvis on radiographs, MRI and CT. MRI may be necessary to diagnose spinal cord compression by the soft tissue component of the tumor.
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Terminology
Myelomas may be referred to as a single site (termed plasmacytoma, plasma cell tumor, or myeloma) or more commonly in multiple sites (multiple myeloma, multicentric plasma cell tumor). There is a larger group of diseases called myeloma related disorders, most of which are not detectable on imaging modalities.
Epidemiology
Middle aged to older large breed dogs, horses, and rarely in cats.
Clinical presentation
Clinical signs may be due to the bone lesions or the circulating globulins. Common presenting signs include lethargy, inappetance, fever, pain from lytic lesions and pathologic fractures, and neurologic signs from spinal cord compression. Hematologic abnormalities result from hyperviscosity syndrome and include thrombosis and bleeding, with possible extension to the brain and eye causing depression and blindness. Hypercalcemia from bone lysis and deposition of protein in the kidneys may cause polyuria and polydipsia.
Pathology
Myeloma is a malignant plasma cell tumor that occurs in active bone marrow, often at multiple sites. The tumor secretes a clonal immunoglobulin (monoclonal M-protein) detectable by serum electrophoresis.
In human cell culture, contact between myeloma cells and osteoclasts promotes myeloma proliferation and osteoclast survival. Osteoclasts cause osteolysis resulting in the lytic lesions seen on imaging, as well as pain, hypercalcemia, and increased ALP. (Boes)
Molecular causes of multiple myeloma may include cellular control such as cyclin D1 and receptor tyrosine kinase dysregulation. Chronic infections, immune stimulation, exposure to radiation, agricultural industry and petroleum products have been associated with multiple myeloma in mice and people. Plasma cell tumors have been reported to progress to multiple myeloma in dogs and cats. (Withrow)
Location
Canine multiple myeloma occurs in the axial skeleton with 25-75% of animals having radiographically detectable bone lesions.(Vail). 50% of dogs with vertebral lesions have neurologic signs due to spinal cord compression or pathologic fracture causing pain. (MacEwan). Lesions may also occur in the liver and spleen.(Wyatt)
In dogs, the majority of lesions are located in the T3-L3 region. Additional locations include pelvis, sacrum, scapula, sternum, ribs.
Feline multiple myeloma occurs both in the bone marrow and in extramedullary locations such as the spleen, skin, liver and lymph nodes. One study reported approximately half of cats had radiographic bone lesions. (Patel)
Classification
1. Well-differentiated myeloma related disorder - <15% plasmablasts
2. Intermediate-grade myeloma related disorder - 15-49% plasmablasts
3. Poorly differentiated myeloma related disorder - >= 50% plasmablasts
(Mellor)
Macroscopic appearance
Non-musculoskeletal areas of involvement appear as splenomegaly, hepatomegaly, and lymphadenopathy.
Microscopic appearance
Clusters of abnormal, frequent (>5%of nucleated cells) plasma cells in bone marrow with binucleation, multinucleation, anisocytosis, and anisokaryosis. On histopathology clusters of plasma cells in proximity to osteoclasts may indicate bone lysis. (Withrow).
Immunophenotype
Canine plasmacytoma has been shown to express multiple myeloma oncogene 1/interferon regulatory factor 4, CD79a, and less commonly CD20. (Ramos-Vara). The antibody Mum-1p is specific for plasmacytomas with the only other positive tumors being occasional B-cell lymphoma.
Feline myeloma related disease had majority light-chain labeling with slightly fewer having heavy chain labeling, majority gamma. In one group of 19 cats twelve had neither CD79a nor CD3, and the remainder had CD79a with one mixed case.
Markers
Monoclonal protein (M protein, paraprotein) in serum, clonal immunoglobulin light chains (Bence Jones Proteins) in urine. Biclonality is also possible, representing development of 2 neoplastic clones.
Genetics
German shepherd dogs were overrepresented in ones study. There is a report of sibling cases in cats which may indicate a familial disease.
Radiographic features
Imaging features of myeloma affecting the axial skeleton revolve around the alterations of the medullary cavity and cortex, primarily bone loss, from osteoclastic activity. The lesions may be monostotic (plasmacytoma) or polyostotic (multiple myeloma) and are classified as aggressive, being primarily lytic. The skeleton may also appear diffusely osteopenic in some cases.
Extramedullary sites of plasmacytoma or multiple myeloma may diffusely involve solid organs such as spleen, liver, or lymph nodes.
Radiography
Survey radiographs of the skull, spine, pelvis, thorax, and scapula may reveal radiographic lesions. There is a moth eaten lysis of vertebral bodies or vertebral processes, and/or other bones including ribs, skull and sternum. The thinner regions of bone such as the spinous processes make the lesions easier to see in this region. The vertebral body is also frequently affected and may appear radiolucent or sclerotic. Alterations in shape may occur such as in pathologic fracture or compression fracture. Proliferative bone lesions in other locations have rarely been reported. (Rankin)
Ultrasound
A spleen infiltrated with myeloma may appear normal, heterogeneous, or coarse, or contain multifocal hypoechoic regions. The liver may be hyperechoic with or without nodules. Renomegaly or lymphadenomegaly may be present in cats. (Nyland, Vail)
CT
Lysis of involved bones with associated soft tissue mass. (eg. pelvis, Marchegiani)
MRI
Vertebral bodies are asymmetrically but diffusely affected with expansile lesions that may not extend beyond the cortical margin, but cause spinal cord compression. Spinal cord compression is also caused by extradural soft tissue masses adjacent to these sites. Compression fractures of vertebral bodies are also possible.
T1
Hyperintense, isointense, or hypointense to spinal cord.
T1+C
Homogeneous, mild to marked contrast enhancement.
T2
Mainly hyperintense to isointense to spinal cord, STIR hyperintense.
Nuclear medicine
Bone scans are not usually positive because of the primarily lytic nature of the bone lesions and lack of osteoblastic activity.
PET/CT is used in human medicine but has not been reported in the veterinary literature.
Radiology report
Radiology report introduction text. Bulleted list of items to include in report.
Morphology
- Permeative or geographic osteolysis of the axial skeleton
- Aggressive monostotic or polyostotic lesions
- Pathologic fracture, compression fracture
- Expansile lesion of the vertebral body or lamina encroaching on spinal cord
Relationship to/involvement of
- Vertebral body to spinal cord and spinal canal
- Regional lymph nodes
Extension
- Extension of soft tissue mass into the extradural space with spinal cord compression
Treatment and prognosis
Treatment and prognosis text. Standard treatments, normal and abnormal post-treatment imaging features, features that relate to prognosis.
Standard treatment involves chemotherapy (melphalan and prednisone) to reduce tumor burden, improve pain, and limit complications. Fractures may be stabilized and treated with radiation therapy. In people, bisphosphonate drugs are promising to limit the skeletal progression of myeloma, but have not been evaluated in dogs.
Prognosis in dogs is good for complete or partial remission with a low rate of non-responders. Median survival time is 540 days. Cats mostly undergo a partial response and most survive for a maximum of 4 months, though survival of over a year has been reported.
Complications
- Bleeding diathesis (epistaxis, platelet dysfunction), clots, hypertrophic cardiomyopathy
- Renal deposition of protein leading to renal insufficiency
- Anemia
- Immunodeficiency - pneumonia and urinary tract infections reported in people
Differential diagnosis
Differential diagnosis text. Default is radiological differential diagnosis list, elaborate for general imaging or specific modality when needed.
- Metastatic neoplasia (carcinoma, sarcoma). Metastatic neoplasia is more common than primary neoplasia, and have a predisposition to the lumbar spine. These are most often primarily lytic lesions.
Primary bone neoplasia (monostotic lesion). Sarcomas are the most common primary vertebral neoplasms, however tend to be proliferative and occur most commonly in the thoracic spine.
Normal variant - coarse trabecular pattern in older animals, thinner regions of spinous process normally seen in C2 and T10.
Practical points
Diagnosis is usually obtained by bone marrow sampling
Rarely bone biopsy of the lytic lesions is necessary
Occasionally splenic aspirate may be helpful
See also
- Bulleted list of related articles
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