Oncology · Plasma Cell Dyscrasias
The facts most likely to be tested
Multiple myeloma is characterized by the CRAB criteria: hypercalcemia, renal insufficiency, anemia, and lytic bone lesions.
The classic radiographic finding is lytic bone lesions on skeletal survey, which are typically punched-out and do not show osteoblastic activity on bone scan.
Serum protein electrophoresis (SPEP) typically reveals an M-spike, representing a monoclonal immunoglobulin (usually IgG or IgA).
Bone marrow biopsy is diagnostic when it demonstrates clonal plasma cells comprising greater than 10% of the marrow cellularity.
Peripheral blood smear often shows rouleaux formation due to high levels of circulating paraproteins increasing erythrocyte sedimentation rate.
Urinalysis frequently reveals Bence Jones proteins, which are monoclonal free light chains that are not detected on standard urine dipstick.
Patients are at high risk for pathologic fractures and spinal cord compression due to extensive skeletal involvement and osteoclast activation.
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A 68-year-old male presents with persistent lower back pain and generalized fatigue. Laboratory studies reveal a hemoglobin of 9.2 g/dL, serum calcium of 11.8 mg/dL, and a creatinine of 2.1 mg/dL. A skeletal survey demonstrates multiple punched-out lytic lesions in the skull and proximal humerus. Serum protein electrophoresis shows a prominent M-spike.
What is the most likely diagnosis?
Multiple myeloma
The patient meets the CRAB criteria (hypercalcemia, renal failure, anemia, and lytic bone lesions) and exhibits the classic M-spike, which is diagnostic for multiple myeloma.
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Etiology / Epidemiology
Malignancy of plasma cells in older adults (median age 65-70). Higher incidence in African Americans.
Clinical Manifestations
CRAB criteria: Calcium elevation, Renal failure, Anemia, Bone lesions. Rouleaux formation on smear.
Diagnosis
Serum protein electrophoresis (SPEP) showing M-spike. Bone marrow biopsy with >10% clonal plasma cells.
Treatment
Bortezomib + Lenalidomide + Dexamethasone. Autologous stem cell transplant for eligible patients.
Prognosis
Median survival 5-7 years. Pathologic fractures and recurrent infections are primary mortality drivers.
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Epidemiology & Etiology
Primarily affects older adults with a median age of 65-70 years. It is significantly more common in African Americans compared to other ethnic groups. The etiology involves the clonal proliferation of malignant plasma cells in the bone marrow.
Pertinent Anatomy
The disease primarily targets the axial skeleton (vertebrae, skull, ribs, pelvis). Infiltration of the bone marrow space leads to the displacement of normal hematopoietic tissue.
Pathophysiology
Malignant plasma cells produce excessive monoclonal immunoglobulins (M-protein). These cells secrete cytokines that activate osteoclasts and inhibit osteoblasts, causing lytic bone lesions. Renal damage occurs via Bence-Jones protein (light chain) precipitation in the distal tubules.
Clinical Manifestations
Patients present with the CRAB mnemonic: Calcium elevation, Renal failure, Anemia, and Bone pain. Physical exam may reveal bone tenderness, while peripheral smear shows Rouleaux formation due to high protein levels. Spinal cord compression and hyperviscosity syndrome are critical emergencies.
Diagnosis
The gold standard for diagnosis is a bone marrow biopsy demonstrating >10% clonal plasma cells. SPEP is the initial screening test, typically revealing an M-spike. Skeletal survey (or low-dose CT) is required to identify lytic lesions; avoid bone scans as they are insensitive.
Treatment
Initial therapy consists of a triplet regimen: Bortezomib, Lenalidomide, and Dexamethasone. Autologous stem cell transplant is the standard of care for transplant-eligible patients. Bisphosphonates are indicated to prevent skeletal-related events, but monitor for osteonecrosis of the jaw.
Prognosis
Prognosis is stratified by cytogenetics, with del(17p) and t(4;14) indicating poor outcomes. Key complications include pathologic fractures, recurrent bacterial infections, and acute kidney injury.
Differential Diagnosis
MGUS: M-spike <3g/dL and <10% plasma cells without CRAB symptoms
Waldenström macroglobulinemia: IgM spike with hyperviscosity, no lytic bone lesions
Metastatic carcinoma: Usually osteoblastic lesions, not lytic
Amyloidosis: Associated with light chain deposition, often presents with macroglossia
Smoldering myeloma: M-spike >3g/dL or 10-60% plasma cells without CRAB