Multiple Myeloma
Direct answer
Multiple myeloma is a clonal proliferation of malignant plasma cells in the bone marrow that produces a monoclonal immunoglobulin (M-protein), typically in older adults presenting with bone pain, anaemia, renal impairment and hypercalcaemia. Diagnosis requires bone marrow clonal plasma cells at or above 10% (or a plasmacytoma) plus a myeloma-defining event — the CRAB features — with an M-spike on serum electrophoresis and punched-out lytic bone lesions as the classic signatures. Transplant-eligible patients receive bortezomib-based induction — commonly with lenalidomide and dexamethasone — followed by autologous stem-cell transplantation.
What you must remember
- CRAB criteria: hyperCalcaemia, Renal failure, Anaemia and Bone (lytic) lesions — the end-organ effects that define symptomatic disease.
- M-protein: monoclonal spike on serum protein electrophoresis, characterised by immunofixation; IgG is the commonest type; light-chain-only disease secretes Bence Jones protein, found in urine.
- Blood film: rouleaux formation of red cells with a markedly raised ESR; normal immunoglobulins are suppressed (immunoparesis), predisposing to infections with encapsulated organisms.
- Marrow findings: clonal plasma cells at or above 10%, expressing CD138 (syndecan-1) and CD38; serum free light chain assay and ratio support diagnosis and monitoring.
- Bone disease: osteolytic punched-out lesions (skull classic), bone pain the commonest presentation, pathological fractures, and spinal cord compression a radiation-treatment emergency; alkaline phosphatase is characteristically normal because osteoblastic activity is absent.
- Myeloma-defining biomarkers: marrow plasma cells at or above 60%, serum free light chain ratio at or above 100, or more than one focal MRI lesion — allowing treatment before CRAB features appear.
- Renal disease: light-chain cast nephropathy is the commonest lesion; hydration and avoiding NSAIDs and contrast protect the kidneys.
Common confusion
The plasma cell spectrum trips candidates: MGUS has M-protein below 30 g/L, marrow plasma cells below 10% and no end-organ damage; smouldering myeloma exceeds those thresholds but still lacks CRAB features or biomarkers; multiple myeloma requires the defining events. Waldenström macroglobulinaemia secretes IgM (not IgG or IgA), presents with hyperviscosity and lymphoplasmacytic marrow, and does not cause lytic lesions. Bone metastases contrast: predominantly osteoblastic or mixed, alkaline phosphatase raised, and a primary tumour (prostate, breast, lung, thyroid, kidney) usually identifiable.
Exam-focused takeaway
NEET-PG questions on myeloma cluster around a few types: a CRAB-featured vignette asking the most likely diagnosis, electrophoresis and urine light-chain interpretation, rouleaux on a blood film image, the diagnostic marrow threshold and CD138 marker, and radiographs of the skull with punched-out lesions. Clinical-science stems ask why alkaline phosphatase is normal, why infections recur (humoral immunodeficiency), and what defines the MGUS-smouldering-treatment boundary. Management questions stick to principles: bortezomib-based induction with autologous transplantation for eligible patients, bisphosphonates or denosumab for bone disease (watch for osteonecrosis of the jaw), hydration and hypercalcaemia control.
Practise previous-year and exam-style myeloma questions inside the PrepElephant app — topic-wise banks, image-rich practice, full-length mocks and spaced revision of flagged stems.
Frequently asked questions
What are the CRAB criteria?
Hypercalcaemia, renal failure, anaemia and bone lesions — the myeloma-defining end-organ effects.
What is M-protein and Bence Jones protein?
M-protein is the monoclonal immunoglobulin spike on serum electrophoresis; Bence Jones protein is monoclonal free light chain excreted in urine.
What is the commonest presentation of multiple myeloma?
An older adult with persistent back or chest bone pain, often with anaemia; lytic lesions or pathological fractures may be the first clue.
Which markers identify plasma cells?
CD138 (syndecan-1) and CD38 are the standard markers; clonal plasma cells at or above 10% with a myeloma-defining event establish diagnosis.
How do MGUS and smouldering myeloma differ from treated disease?
MGUS and smouldering myeloma lack CRAB features and myeloma-defining biomarkers; only end-organ damage or those biomarkers justify treatment.
Why is alkaline phosphatase normal in myeloma bone disease?
Myeloma stimulates pure osteoclastic resorption without osteoblastic new-bone formation, so the osteoblast enzyme remains normal — unlike in bone metastases.
Practise this in the PrepElephant app
Question banks, previous-year questions, mock tests and revision tools — for Multiple Myeloma and Pathology. Free to start.