STEPTRACKERHEMATOLOGY + ONCOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Plasma Cell Dyscrasias

One plasma cell clone, one immunoglobulin — from silent MGUS to multiple myeloma, plus Waldenström, amyloid and POEMS.

FOCUS ON
Myeloma = CRAB: hyperCalcemia, Renal failure, Anemia, Bone lytic lesions. Add rouleaux, Bence Jones light chains, and infections as the main cause of death. Separate MGUS by thresholds, and Waldenström by IgM hyperviscosity without lytic lesions.
DISORDER
DEFINITION · MECHANISM
FEATURES
LABS · TREATMENT
Multiple myeloma
older adults
Clonal plasma cells ≥ 10% of marrow + end-organ damage; M-protein (IgG > IgA) and/or free light chains.
Ca²⁺ ↑ (RANKL, IL-6) · Renal (light-chain casts) · Anemia · Bone: punched-out lytic lesions, fractures, back pain
More common in Black patients · bortezomib, lenalidomide, dexamethasone, autologous transplant, bisphosphonates
Myeloma — other findings
Normal immunoglobulins are suppressed.
Recurrent infections (leading cause of death), AL amyloid, hyperviscosity (rare)
Rouleaux, ↑ ESR, ↑ total protein, low anion gap; Bence Jones proteinuria (dipstick misses it)
MGUS
premalignant
M-protein < 3 g/dL, < 10% marrow plasma cells, no CRAB.
Very common in the elderly; asymptomatic
~1%/year progress to myeloma · monitor
Smoldering myeloma
M-protein ≥ 3 g/dL or 10–60% plasma cells, no CRAB.
Asymptomatic
Higher progression risk than MGUS
Solitary plasmacytoma
Single bone or soft-tissue plasma cell tumor without marrow disease.
Extramedullary forms often in upper airways
Radiation; may progress to myeloma
Waldenström macroglobulinemia
Lymphoplasmacytic lymphoma secreting IgM; MYD88 L265P.
Hyperviscosity (blurred vision, headache, bleeding, retinal vein engorgement), Raynaud (cryoglobulins), neuropathy, nodes and spleen
No lytic lesions, no hypercalcemia · plasmapheresis for hyperviscosity; rituximab, BTK inhibitors
AL amyloidosis
Light chains (λ > κ) misfold and deposit.
Nephrotic syndrome, restrictive cardiomyopathy, macroglossia, periorbital purpura
Congo red apple-green — page 1.07
POEMS syndrome
Plasma cell disorder with sclerotic (not lytic) bone lesions; high VEGF.
Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes
Neuropathy + sclerotic bone lesion + λ M-protein
Workup
Serum and urine protein electrophoresis, immunofixation, free light-chain ratio.
Marrow biopsy; skeletal survey, PET or MRI
Plasma cells: eccentric nucleus, "clock-face" chromatin, perinuclear hof; CD138⁺

Mechanism — how one clone causes CRAB

Plasma cell cloneIL-6 keeps it alive
→
RANKL ↑, OPG ↓Osteoclasts fire
→
Lytic lesionsHypercalcemia, fractures
Free light chains
→
Tubular castsRenal failure
Marrow crowdingAnemia
Normal Ig ↓Infections

MGUS vs smoldering vs myeloma

FEATURE
MGUS
SMOLDERING
MYELOMA
M-protein
< 3 g/dL
≥ 3 g/dL
Any
Marrow plasma cells
< 10%
10–60%
≥ 10%
CRAB / organ damage
None
None
Present
Management
Monitor
Close follow-up
Treat

How it's tested

COMMON CONFUSIONMyeloma bones are lytic, with low bone formation, so the alkaline phosphatase is often normal and bone scans can look normal. Skeletal survey or MRI finds the lesions.
THE TRAPProteinuria missed on dipstick but found on urine electrophoresis is Bence Jones protein. Dipsticks detect albumin, not light chains.
YOUR APPROACHFind the M-protein, name its class (IgM vs IgG/IgA), check for CRAB, then classify as MGUS, smoldering or myeloma.

If you see… think…

70-year-old with back pain, ↑ Ca²⁺, ↑ creatinine, anemia, rouleaux → multiple myeloma
Punched-out lytic lesions in the skull → myeloma
Urine light chains with a negative dipstick → Bence Jones proteinuria
M-spike 1.2 g/dL, 4% plasma cells, no symptoms → MGUS — monitor
IgM spike, blurry vision, nosebleeds, no bone lesions → Waldenström — plasmapheresis
Myeloma with macroglossia and nephrotic syndrome → AL amyloidosis
Myeloma patient with recurrent pneumococcal pneumonia → functional hypogammaglobulinemia
Unexpectedly low anion gap → cationic IgG paraprotein
Neuropathy + sclerotic bone lesion + M-protein → POEMS syndrome
Proteasome inhibitor for myeloma → bortezomib