Chapter 27: Multiple Myeloma

Epidemiology

Pathology

Monoclonal gammopathy of uncertain significance (MGUS)

• Stable serum M-protein level <3 g/dL and bone marrow clonal plasma cells <10%

• Urine Bence Jones protein absent or minimal

• No related organ/tissue impairment (ROTI)^✫

• No evidence of other B-lymphoproliferative disorders

• Progression to multiple myeloma (MM) in ~1% per year (median 10 years)

Smoldering (asymptomatic) myeloma

• M-protein in serum ≥30 g/L and/or bone marrow clonal plasma cells ≥10%

• No ROTI or symptoms

Active (symptomatic) myeloma^†

• Requires one or more of the following (CRAB criteria):

• Calcium elevation (>11.5 mg/dL [>2.88 mmol/L])

• Renal insufficiency (creatinine >2 mg/dL [>177 μmol/L])

• Anemia (hemoglobin <10 g/dL or 2 g less than normal)

• Bone disease (lytic or osteopenic)

Extramedullary plasmacytoma

• Extramedullary tumor of clonal plasma cells

• Normal bone marrow

• Normal skeletal survey

• M-protein absent or disappears from blood/urine after excision or irradiation of solitary lesion

• Absence of ROTI^✫

• Progression to MM in ~15%

Solitary plasmacytoma of bone

• Three to 5% of plasma cell dyscrasias

• Isolated bone tumor consisting of monoclonal plasma cells

• Normal bone marrow

• M-protein absent or disappears from blood/urine after excision or irradiation of solitary lesion

• Absence of other myeloma ROTI^✫

• Multiple or recurrent in up to 5% of patients

• Progression to MM in ~50%

Plasma cell leukemia

• Five percent of newly presenting MM patients

• Peripheral blood absolute plasma cell count ≥2000/mm³

• More than 20% plasma cells in differential count of peripheral blood leukocytes

Work-up

All patients

1. H&P

2. CBC with differential; serum electrolytes, BUN, creatinine, calcium and albumin, LDH

3. Quantitative immunoglobulins, serum protein electrophoresis, and immunofixation

4. Twenty-four–hour urine protein electrophoresis, immunofixation, and Bence Jones quantitation

5. Serum free light-chain assay

6. Skeletal survey

7. Unilateral bone marrow aspirate and biopsy with flow and immunohistochemistry

8. Bone marrow cytogenetics and interphase FISH

9. Albumin and β₂-microglobulin (see staging system)

Selected patients

1. MRI of the spine (evaluate for solitary plasmacytoma of bone or suspected cord compression)

2. FDG-PET/CT scan in selected patients to evaluate for increased uptake

3. Tissue biopsy (evaluate for solitary plasmacytoma)

4. Serum viscosity (if M-protein level is markedly elevated or symptoms of hyperviscosity are present)

5. Additional tests (prognostic markers): plasma cell labeling index, C-reactive protein, and LDH

Staging