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Stem
A 67-year-old man presents to the emergency department with six weeks of worsening lower-back and rib pain, fatigue and constipation. He has had two episodes of pneumonia in the past year. On examination he is pale, with bony tenderness over the lumbar spine and ribs; he is confused (new-onset disorientation). Investigations: haemoglobin 88 g/L (MCV 87 fL), ESR 118 mm/h, creatinine 210 micromol/L, corrected calcium 3.2 mmol/L, albumin 30 g/L. Blood film shows rouleaux formation. Urine dipstick is negative for protein.
Questions
a) What is the most likely diagnosis, and which four features of end-organ damage support it? (2 marks)
Most likely diagnosis is symptomatic multiple myeloma. The end-organ damage follows the CRAB mnemonic, all present here: C — hypercalcaemia (3.2 mmol/L, causing the confusion and constipation); R — renal impairment (creatinine 210); A — anaemia (normocytic, 88 g/L); B — bone disease (back and rib pain with bony tenderness).
b) Outline the investigations you would order to confirm the diagnosis and assess risk. (4 marks)
- Serum protein electrophoresis (SPEP) + immunofixation — to detect and type the monoclonal protein (M-band; IgG commonest).
- Serum free light chain assay with kappa/lambda ratio — essential because a urine dipstick misses Bence Jones protein (light chains) and some myelomas are light-chain-only.
- Urine electrophoresis (UPEP) of a 24-hour collection — Bence Jones proteinuria.
- Bone-marrow aspirate and trephine biopsy — clonal plasma cells (CD138/CD38 positive, aberrant CD56) and percentage; FISH cytogenetics on purified plasma cells for high-risk lesions (del(17p)/TP53, t(4;14), t(14;16), gain(1q)).
- Whole-body low-dose CT (or MRI spine for cord/focal lesions, or PET-CT) — to define lytic/focal lesions and exclude cord compression.
- Baseline bloods: urea/electrolytes, calcium, LDH, beta-2 microglobulin, albumin, CRP — for the Revised International Staging System (R-ISS) and prognostic stratification.
c) Describe the stepwise definitive management for this fit, transplant-eligible patient. (3 marks)
- Induction with VRd (bortezomib + lenalidomide + dexamethasone) for 4 to 6 cycles.
- Stem-cell mobilisation and harvest, then high-dose melphalan conditioning followed by autologous stem-cell transplant (ASCT).
- Lenalidomide maintenance until progression.
- Supportive care: zoledronic acid (or denosumab) to reduce skeletal events and hypercalcaemia; treat the hypercalcaemia (IV saline + bisphosphonate); avoid NSAIDs/contrast for the renal failure; aciclovir prophylaxis (bortezomib — herpes zoster) and VTE prophylaxis (lenalidomide).
d) State two diagnostic pitfalls specific to this disease. (1 mark)
- A normal SPEP does not exclude myeloma — light-chain and non-secretory disease are missed unless serum free light chains are added.
- Urine dipstick is negative in light-chain (Bence Jones) myeloma because dipsticks detect albumin, not light chains; use UPEP.