Multiple Myeloma
description
Transcript of Multiple Myeloma
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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