Paper I
Question
A 60-year-old man presents to the medical OPD with complaints of easy fatiguability, bone pain and decreased urination. On examination, he has pallor. Systemic examination is normal. Hemogram shows Hb- 8gm%, TLC of 6500/mm3 and platelet count of 1,60,000/mm3. The differential leucocyte count is normal. Peripheral smear shows increase in Rouleaux formation. ESR is 110mm/first hour. Serum Creatinine of
Answer
Diagnosis: Multiple Myeloma
The clinical and laboratory picture is classic for multiple myeloma:
- Elderly patient with anaemia (Hb 8 g%), bone pain (lytic lesions), and renal impairment (decreased urination) — the classic “CRAB” features (hyperCalcaemia, Renal insufficiency, Anaemia, Bone lesions) of myeloma
- Normal TLC, platelet count, and differential count — anaemia is isolated, not part of pancytopenia, as expected in myeloma (marrow infiltration is focal/plasmacytic rather than globally suppressive early on)
- Markedly elevated ESR (110 mm/1st hour) with increased rouleaux formation on peripheral smear — both classic findings due to the high concentration of monoclonal immunoglobulin (M-protein) raising plasma viscosity and promoting red cell aggregation
- Raised serum creatinine — reflects myeloma-associated renal impairment (“myeloma kidney”/cast nephropathy from light chains, plus hypercalcaemia-related nephrotoxicity)
Pathogenesis
- Neoplastic proliferation of a single clone of plasma cells in the bone marrow, producing a monoclonal immunoglobulin (M-protein) or its light chain component (Bence Jones protein)
- Malignant plasma cells secrete cytokines (notably IL-6, RANKL) that activate osteoclasts, causing lytic bone lesions, bone pain, and hypercalcaemia
- Excess free light chains are filtered by the kidney, causing direct tubular toxicity and obstructive cast formation (“myeloma kidney”), and may deposit as AL amyloid
Laboratory/diagnostic workup
- Serum protein electrophoresis — M-spike (monoclonal band, usually IgG or IgA)
- Urine Bence Jones protein (free light chains)
- Bone marrow aspiration/biopsy — increased plasma cells (>10%), often atypical/abnormal forms
- Skeletal survey/imaging — punched-out lytic lesions, especially in the skull (“raindrop skull”), vertebrae, pelvis
- Serum calcium, creatinine, beta-2 microglobulin (prognostic marker)
- Serum free light chain assay
Peripheral smear correlate
- Marked rouleaux formation (red cells stacking like coins) — a direct consequence of elevated serum globulin/M-protein reducing the zeta potential between red cells, promoting their aggregation; this is also the mechanism behind the markedly elevated ESR