Multiple Myeloma
The plasma-cell clone — from the M-spike on electrophoresis to the CRAB criteria and the diagnostic triad.
A 60-year-old with fatigue
No past history — but the labs tell a whole story at once.
| Test | Value | Interpretation |
|---|---|---|
| Hemoglobin | 10.6 g/dL | Anemia |
| Creatinine | 1.8 mg/dL | Renal insufficiency |
| Calcium | 11.2 mg/dL | Hypercalcemia |
| Total protein | 11 g/dL | High (albumin low at 3.1) |
Serum electrophoresis shows a monoclonal IgA paraprotein — a massive tumour burden hiding behind vague fatigue.
The plasma cell
The terminal B-cell — the body’s antibody factory, normally 3–5% of marrow, secreting a diverse (polyclonal) mix of immunoglobulins.
Normal · polyclonal
Many different plasma cells make many different antibodies to fight infection.
Malignant · monoclonal
One clone replicates without limit, secreting a single identical immunoglobulin — the paraprotein / M-protein.
The M-spike on electrophoresis
Serum proteins separate by charge into bands — albumin to gamma. A monoclonal protein piles up as a tall, narrow spike in the gamma region. Toggle the tracing.
The spike measures the physical quantity of monoclonal protein — identified by its heavy chain (usually IgG or IgA; IgM suggests Waldenström’s).
From MGUS to symptomatic myeloma
The same clone, escalating. What separates “observe” from “treat” is end-organ damage. Step through the staircase.
MGUS
- M-spike < 3 g/dL
- < 10% marrow plasma cells
- Asymptomatic
Manage: observe.
Smoldering myeloma
- M-spike ≥ 3 g/dL or ≥ 10% plasma cells
- Still asymptomatic
Manage: observe.
Multiple myeloma
- M-spike ≥ 3 g/dL or ≥ 10% plasma cells
- + symptoms (CRAB)
Manage: treat.
The CRAB criteria
Symptomatic myeloma is defined by end-organ damage — four pillars that explain the whole clinical picture.
C · Calcium
Hypercalcemia — leached from destroyed bone.
R · Renal
Renal insufficiency — cast nephropathy.
A · Anemia
Marrow infiltration + low EPO.
B · Bone
Lytic lesions, fractures.
Punched-out lytic lesions
Myeloma tips bone remodelling — up osteoclast (eating), down osteoblast (building).
Consequences
- Diffuse osteopenia
- Lytic “punched-out” lesions
- Pathological fractures
- Hypercalcemia
The imaging
Lateral skull X-ray — multiple punched-out defects.
Cast nephropathy & rouleaux
Renal · cast nephropathy
Light chains bind Tamm–Horsfall protein in the tubules, forming insoluble casts that obstruct flow. Worsened by hypercalcemia, hyperviscosity, NSAIDs.
Anemia & infection
Normocytic anemia from marrow infiltration + low EPO. Immunodeficiency because the clonal antibody is useless and normal immunoglobulins are suppressed.
Cord compression & neuropathy
Spinal cord compression
From paraspinal masses or vertebral collapse — a medical emergency.
Peripheral neuropathy
Direct nerve damage by monoclonal protein, or a chemotherapy side effect.
Differential: Waldenström’s
| Multiple myeloma | Waldenström’s |
|---|---|
| IgG or IgA | IgM (large pentamer) |
| Lytic bone lesions | Hyperviscosity syndrome |
| — | Organomegaly (spleen / liver) |
| — | No lytic bone lesions |
Hyperviscosity engorges retinal veins — the “sausage-link” fundus.
The diagnostic triad
Symptomatic myeloma needs all three.
1 · Monoclonal protein
M-spike > 3 g/dL (or urinary Bence-Jones).
2 · Marrow clones
> 10% CD138⁺ plasma cells on biopsy.
3 · End-organ damage
CRAB features present.
M-spike 60 g/L ✓ · anemia + renal + hypercalcemia ✓ → symptomatic multiple myeloma, requiring treatment.
Epidemiology & takeaway
Who
Median age 65–70; slight male predominance.
How common
1% of all malignancies; 10% of hematologic cancers.
Why
Usually unknown; links to radiation, benzene, chronic antigen stimulation.
“Recognise the journey from silent MGUS to the toxic end-organ damage of symptomatic myeloma.”
End of lecture.
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