Family Medicine Board Review · Hematology / Oncology · Source: AAFP 2017

Multiple Myeloma: High-Yield Board Summary

Plasma cell malignancy in one page — definition, CRAB criteria, presentation frequencies, and the exact diagnostic test panel, all board-trap annotated.

Definition Complications CRAB & Presentation Diagnosis Lab Pattern

Definition

Multiple myeloma = malignancy of plasma cells.

Median age of diagnosis ≈ 70 years old — think of it as a disease of older adults, alongside CLL and AML.

Complications — Mechanism-Based

Malignant plasma cells produce a monoclonal protein — an abnormal immunoglobulin or free light chain (kappa or lambda) — that causes hyperviscosity and end-organ damage
Invasive bone disease → pathologic fractures, bone pain, osteoporosis, and hypercalcemia
Bone marrow invasion → anemia; immunologic changes → recurrent infections

Board trap: the anemia and infections aren't just "cancer fatigue" — they're mechanistically tied to bone marrow crowding out normal hematopoiesis and normal immunoglobulin production, respectively.

Clinical Presentation — CRAB

CHypercalcemia

RRenal insufficiency

AAnemia

BLytic bone lesions / back pain

Also watch for hyperviscosity syndrome: dyspnea, transient ischemic attack, retinal hemorrhage, deep venous thrombosis.

Table 1 — Findings on Presentation

Frequency of Presenting Symptoms/Labs

Anemia (Hgb <12 g/dL)

73%

Bone pain

58%

Elevated creatinine (>1.3 mg/dL)

48%

Fatigue / generalized weakness

32%

Hypercalcemia (>10.1 mg/dL)

28%

Weight loss

24%

Board trap: anemia (73%) is actually the most common presenting finding — more common than bone pain or hypercalcemia. Don't assume CRAB letters are equally frequent; A and R both outrank C in real-world presentation data.

Diagnosis

Peripheral Smear

Characteristic rouleaux formation — RBCs stacking like coins, driven by elevated serum protein/monoclonal immunoglobulin.

Confirmatory

Bone marrow aspiration and biopsy confirms the diagnosis.

Serum Testing

Serum protein electrophoresis (SPEP) → M spike (monoclonal spike).

Urine Testing

Urine protein electrophoresis (UPEP) → Bence Jones proteins (free light chains in urine).

Board trap: patients have normal ALP and phosphate despite lytic bone lesions — this distinguishes myeloma bone disease from other causes of bone destruction/metabolic bone disease where ALP is often elevated (e.g., Paget disease, osteoblastic metastases).

Full Diagnostic Test Panel (Table 2)

Initial Tests	Confirmatory Tests	Oncology-Ordered Tests	Special Circumstances
CBC with differential Serum albumin, calcium, creatinine, electrolytes, BUN	24-hour urine protein Beta-2 microglobulin LDH Serum free light chain assay Serum immunofixation electrophoresis Serum protein electrophoresis* Skeletal survey Urine immunofixation electrophoresis Urine protein electrophoresis	Bone marrow aspirate and biopsy with cytogenetics, flow cytometry, FISH, and/or immunohistochemistry	Bone densitometry PET/CT or whole-body MRI Serum viscosity Tissue biopsy of bony or other lesion

Suggestive Lab Pattern

LFT / Protein Panel Clue

High total protein
Low albumin
High globulin
Low A/G ratio (<1) — the globulin fraction (largely the monoclonal protein) outweighs albumin

Exam pearl: if a routine metabolic/LFT panel shows an unexpectedly elevated total protein with a normal-to-low albumin, calculate the A/G ratio — a ratio <1 should immediately raise suspicion for multiple myeloma and prompt SPEP/UPEP.

Evaluation Logic — Quick Reference

Nonspecific symptoms (fatigue, weight loss, recurrent infections, dyspnea, nausea, vomiting) → initial labs/imaging; if abnormal → myeloma-directed workup
Bone symptoms (bone pain, osteolytic lesion, spinal cord compression, pathologic fracture) → myeloma-directed workup
Asymptomatic lab abnormality (hypercalcemia, renal failure, elevated total protein, monoclonal paraproteinemia) → additional imaging (MRI/PET-CT) and staging
Once myeloma is confirmed and categorized: distinguish from MGUS and smoldering myeloma (both managed with expectant monitoring) vs. active multiple myeloma (symptomatic disease/spinal cord compression → urgent oncology, radiotherapy, or surgical referral)

Board trap: not every monoclonal protein finding is myeloma — MGUS and smoldering myeloma are asymptomatic plasma cell disorders managed with observation, not treatment. Only symptomatic (CRAB-positive) disease gets treated.