Multiple myeloma

What it is

Multiple myeloma is a plasma cell dyscrasia. Its monoclonal antibody is IgG, IgA or light chains, and its bone marrow biopsy shows more than 10% clonal plasma cells.

It is the most common primary malignant bone neoplasm in adults. It arises from red marrow due to the monoclonal proliferation of plasma cells and manifests in a wide range of radiographic abnormalities. Risk sits with age above 40 and with men, at an M:F of 2:1.

How it presents

Osteolytic lesions and fractures, anemia, hypercalcemia, and renal insufficiency.

The initial presentation occasionally is a polyneuropathy. Otherwise it is bone pain, anemia, renal failure, proteinuria and hypercalcemia.

How it is diagnosed

The peripheral smear shows rouleaux: linear aggregates of RBCs that form in the presence of increased plasma proteins, resembling stacks of coins. Rouleaux is not myeloma alone, and the rest of its list has to be weighed. Pregnancy is its most common cause, due to a physiological increase in fibrinogen; inflammatory conditions cause it due to polyclonal immunoglobulins; plasma cell dyscrasias cause it due to monoclonal paraproteinemia, multiple myeloma and macroglobulinemia among them; and it can be a storage artifact. Where the presentation is concerning for multiple myeloma, the next appropriate step along with radiography is serum protein electrophoresis. If laboratory work shows a monoclonal spike, or if a skeletal survey indicates lytic lesions, referral to an oncologist is indicated for a bone marrow biopsy. MRI of the lumbar spine would be premature at that point, and iron studies, a TSH level or a vitamin B12 level would not adequately address the abnormal laboratory studies or facilitate making the diagnosis.

The diagnosis is written as three items. There is a serum or urinary monoclonal protein; there are more than 10% clonal plasma cells in the bone marrow, or a plasmacytoma, with plasma cells above 60% enough on their own, regardless of CRAB; and there is end-organ damage related to the plasma cell dyscrasia. That damage is a named set of four, an increased serum Ca2+, renal failure, anemia and lytic bone lesions, so it is the hypercalcemia among the laboratory findings that shows the end-organ damage, and the rouleaux on the film belongs to the picture rather than to that set.

The investigations are listed in the order they are done. Bone marrow aspirate and biopsy, often showing a focal abnormality, greater than 10% plasma cells, abnormal morphology and clonal plasma cells, sent for FISH and cytogenetics for their prognostic implications. Then the skeletal survey, with MRI if there are symptoms of cord compression, to show lytic lesions and areas at risk of pathologic fracture. Bone scans are not useful, since they detect osteoblast activity. So the imaging asked for on the bones is the skeletal survey and not the bone scan, and the MRI is kept for the cord.

The investigations themselves run in order. CBC shows a normocytic anemia with thrombocytopenia and leukopenia, and the peripheral film shows rouleaux formation. Biochemistry is Ca2+, creatinine, albumin, β2-microglobulin and proteinuria. Then the monoclonal proteins: serum protein electrophoresis (SPEP) demonstrates a monoclonal protein spike in serum, the M protein; urine protein electrophoresis (UPEP) demonstrates light chains in urine, the Bence-Jones protein; immunofixation demonstrates M protein and identifies the Ig type, IgG, IgM and so on, and also identifies the light chains, kappa or lambda; and serum free light chain quantification gives the kappa and lambda light chains ratio.