MULTIPLE MYELOMARick Allen

WHAT IS IT? A malignant proliferation of plasma

cells derived from a single clone, with multifocal involvement of the skeleton.

EPIDEMIOLOGY 1,115 Aussies diagnosed every year Risk increases w. age : 80% are > 60

y.o. Men > women Black 2x > white Familial link (4x increased risk) 1% of all US cancers, 10% of

haemotological cancers

AETIOLOGY Cause is unknown, however there is

evidence for genetic issues; 11q14 and 17p13 deletions (serious) 11q abnormalities T(11;14)(q13;q32) , cyclin D1 (cell cycle

regulatory gene) (less serious) T(4;14)(p16;q32) heavy chain gene and

tyrosine kinase receptor controls cell proliferation

Mys, ras, p53 and Rb-1 mutations

PATHOPHYSIOLOGY Plasma cell attaches to bone marrow

stromal cell (handy because…) Monoclonal Ig (M component) is

produced; potentially with excess heavy/light chains (urine)

Bone destruction (↑ RANKL on OB ↑ OC act., inhibition of OB)

IL-6, IGF-1 the main players

PATHOPHYSIOLOGY

CLINICAL FEATURES Are due to:

Plasma cell growth in tissue Excessive defective Ig production Normal humoral immunity suppression

CLINICAL FEATURES Bone resorption

pathologic fractures and bone pain (usually precipitated by movement). Generalized osteoperosis

hypercalcaemia neurologic symptoms and renal dysfunction ↓ normal Ig production

Recurrent bacterial infection Cell immunity not affected Ig breakdown increased

IgA ↑ blood viscosity headaches, retinopathy, fatigue Renal failure

Multifactorial cause, but primarily due to Bence-Jones proteinuria Toxic atrophy of tubal epithelia, pyelonephritis

Anaemia Due to marrow involvement. Normocytic, normochromic.

Pancytopenia.

CLINICAL FEATURES

MORPHOLOGY Destructive plasma cell tumours in

axial skeleton Medullary cavity erodes spongy

bone destroys cortical bone. Lesions 1-4cm diameter

Soft, gelatinous, red tumour mass Elsewhere, ↑ marrow plasma

cellularity

MORPHOLOGY

DIAGNOSING Radiograph and lab results

24hr urine to find Bence-Jones bodies Electrophoresis to determine monoclonal

Ig/light chains X-rays of osteolytic lesions: require bone

marrow examination to confirm.

DIFFERENTIALS Some lymphomas and leukaemias

(CLL) can also produce M components.

TREATMENT/MANAGEMENT Systemic treatment + symptomatic

treatment Cytotoxic agents (proteasome

inhibitors) Combination chemo: alters myeloma

and stromal cell interaction. Inhibits angiogenesis

Bisphosphonates bone and Ca Transplant: prolongs but no cure Radiotherapy for bone pain

PROGNOSIS Median survival 4-6 years

Multiple bony lesions 6-12 months

Death usually due to either renal failure or infection

SHOULD KNOW A BIT ABOUT… Plasmacytoma

Localised myeloma Have the potential to spread. Easier to treat

if found in soft tissue. Monoclonal Gammopathy of Uncertain

Significance (MGUS) Same genetic abnormalities as MM Asymptommatic w. elevated M components. Progression to MM ~1%. Unpredictable.

REFERENCES Robbins and Cotran, pp 609-611

Harrisons, pp 701-706

Underwood, pp 667-669

Leukaemia association of Australia

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