PA20.3 | Multiple Myeloma — Lab Findings & Diagnosis — Summary & Reflection

REFLECT

Before looking at the summary, take 3 minutes to close your notes and reconstruct the following from memory:

1. Draw a simple flowchart: Normal B-cell → plasma cell → what goes wrong in myeloma.
2. List the CRAB features and for each, write the pathogenetic mechanism in one sentence.
3. Name the three key laboratory findings that would appear on a standard haematology report for a myeloma patient (hint: blood film, biochemistry, and urine).
4. What is the single most important way to distinguish myeloma from MGUS?

This active recall exercise mimics what your clinical exams and OSCEs will ask — pattern recognition built on mechanistic understanding.

KEY TAKEAWAYS

Multiple myeloma is a clonal plasma cell malignancy producing a monoclonal M-protein (most often IgG or IgA) with multifocal bone marrow involvement.

Pathogenesis: Clonal plasma cell proliferation driven by IL-6; osteoclast activation via RANKL with osteoblast suppression via DKK-1 → pure lytic bone disease.

Clinical CRAB mnemonic:
• C — HyperCalcaemia (osteoclast-mediated)
• R — Renal failure (cast nephropathy, amyloid, hypercalcaemia)
• A — Anaemia (marrow replacement)
• B — Bone lytic lesions (punched-out, no sclerosis)

Plus: recurrent infections (immune paresis), hyperviscosity, AL amyloidosis.

Key laboratory findings:
• M-spike on SPEP → confirmed by immunofixation
• Bence-Jones protein (free light chains) in urine — missed by dipstick
• Rouleaux on blood film + markedly elevated ESR
• Bone marrow >10% clonal plasma cells
• β2-microglobulin elevated (prognostic)
• Reversed A:G ratio; raised total protein; hypercalcaemia; elevated creatinine

Diagnosis requires: Clonal plasma cells ≥10% + M-protein + myeloma-defining event (CRAB or biomarker).

Key DDx:
• MGUS — M-protein + <10% plasma cells + NO CRAB → observe only
• Waldenström — IgM paraprotein + lymphoplasmacytic infiltrate + hyperviscosity, NOT lytic bone disease
• Reactive plasmacytosis — polyclonal (broad gamma, not M-spike), <10% plasma cells