Paraproteinemia

Paraproteinemia

John Matthews

Definition of a paraprotein

• A monoclonal immunoglobulin or immunoglobulin light chain in the blood or urine resulting from a clonal proliferation of plasma cells or B-lymphocytes (synonyms: M-band, monoclonal band, monoclonal spike, monoclonal protein)

Identification of paraproteins

• Serum protein electrophoresis

• Immunofixation• Urine protein

electrophoresis

Three major disorders associated with paraproteinemia

• Monoclonal Gammopathy of Undetermined Significance (MGUS)

• Multiple Myeloma • Waldenströms

Macroglobulinemia

Plasma CellNeoplasm

Tumor Effects Paraprotein Effects

Bone lesions (Ca)

Marrow failure

Renal failure

Immune suppression

Hyperviscosity

Amyloid

Multiple Myeloma

Plasmacytoma

Plasma cell

Rouleaux

The peripheral blood fi lm in advanced myeloma

Plasma Cells

The bone marrow aspirate in multiple myeloma

Multiple ‘punched-out’ lytic lesions in the skull in myeloma

Wedgecompressionf racture of athoracicvertebra

• Incidence – 3-6/100,000 – mean age 60: M=F: Black:White 2:1

• Cause – Unknown (?radiation)

• Presentation – Bone pain 60% Anemia 15% Renal

10% Chance 10% Other 5%.

• Diagnosis – 2 of (a) paraprotein (b) bone lesions (c)

plasma cells in BM

Multiple Myeloma

Multiple Myeloma - therapy

• Attack the neoplasm (chemo ASCT)

• Preserve the bones (bisphosphonate)

• Treat problems: (bones, anemia, infection, renal failure, bleeding, hyperviscosity)

• Prognosis: incurable: overall median survival 30 months

Multiple Myeloma and the Kidney

• Obstruction of tubules by light chains

• Tubule-cell damage by light chain

• Light chain deposition • Amyloidosis • Hypercalcemia

Waldenström's Macroglobulinemia(IgM paraprotein)

Lymphoplasmacytoid neoplasm

Tumor E ff ect s Paraprotein EffectsLymphadenopathySplenomegalyMarrow failure (esp anemia)

HyperviscosityNeuropathy

Incidence: circa 10% of MM: elderly: M/F 2/1

Presentation: HVS: fatigue, bleed, neuro, visualdisturbance, Raynaud's

Diagnosis: IgM paraprotein + Bone Marrowlymphoplasmacytoid cells

Therapy: Plasma exchange: chemotherapy

Prognosis: Long survival if HVS controlled

Waldenström's Macroglobulinemia

Stable Paraprotein at low concentration

Not associated with marrow failure

Not causing immunosuppression

Not associated with bone lesions

Marrow plasma cell numbers small

Monoclonal Gammopathy of UncertainSignificance (MGUS) (aka Benign Monoclonal Gammopathy)

Common in elderly (1-3% of population): approx 20% developmultiple myeloma by 15 years

bone marrow failure

pathological fractures

hypercalcemia

bone pain

renal failure

plasmacytoid lymphoma

hyperviscosity

When to suspect a paraproteinemia

If Patient is well No lymphadenopathy, splenomegaly Normal blood count Normal renal function Normal serum calcium Paraprotein is small

Make a provisional diagnosis of MGUS recheck the paraprotein concentration after a

few months

What to do when a paraprotein is discovered

THE END