Multiple Myeloma

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Multiple Myeloma

• Definition B-cell malignancy characterised by
  abnormal proliferation
• of plasma cells able to
  produce a monoclonal
• immunoglobulin ( M protein ).
• Incidence 3 - 9 cases per 100000 population /
  year. More frequent
• in elderly with modest male
  predominance

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Multiple Myeloma

• Clinical forms
• multiple myeloma
• solitary plasmacytoma
• plasma cell leukaemia
• M protein
• is seen in 99 of cases in serum
  and/or urine
• IgG gt 50, IgA 20-25, IgE i IgD 1-3
• light chain 20
• 1 of cases are nonsecretory

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Multiple Myeloma

• Clinical manifestations are related to malignant
  behaviour of plasma
• cells and abnormalities produced by M protein
• plasma cell proliferation
• multiple osteolytic bone
  lesions.
• hypercalcemia.
• bone marrow suppression (
  pancytopenia ).
• monoclonal M protein decreased level of normal
  immunoglobulins
• hyperviscosity

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Multiple Myeloma

• Clinical symptoms
• Bone pains, pathologic fractures
• Weakness and fatigue
• Serious infection
• Renal failure
• Bleeding diathesis

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Multiple Myeloma

• Laboratory tests
• ESR gt 100
• Anaemia, thrombocytopenia
• Rouleaux in peripheral blood smears
• Marrow plasmacytosis gt 10 -15
• Hyperproteinemia
• Hypercalcemia
• Proteinuria
• Azotemia

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Diagnostic Criteria for Multiple Myeloma

• Major criteria
• I. Plasmacytoma on tissue biopsy
• II. Bone marrow plasma cell gt 30
• III. Monoclonal M spike on electrophoresis IgG gt
  3,5g/dl,
• IgA gt 2g/dl, light chain gt 1g/dl in 24h urine
  sample
• Minor criteria
• a. Bone marrow plasma cells 10-30
• b. M spike but less than above
• c. Lytic bone lesions
• d. Normal IgM lt 50mg, IgA lt 100mg, IgG lt 600mg/dl

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Staging of Multiple Myeloma

• Clinical staging
• is based on level of haemoglobin, serum calcium,
  immunoglobulins
• and presence or not of lytic bone lesions
• correlates with myeloma burden and prognosis
• I. Low tumour mass
• II. Intermediate tumour mass
• III. High tumour mass
• subclassification
• A - creatinine lt 2mg/dl
• B - creatinine gt 2mg/dl

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Multiple Myeloma

• Poor prognosis factors
• cytogenetical abnormalities of 11 and 13
  chromosomes.
• beta-2 microglobulines gt 2,5 ug/ml.

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Disorder Associated with Monoclonal Protein

• Neoplastic cell proliferation
• multiple myeloma
• solitary plasmacytoma
• Waldenstrom macroglobulinemia
• heavy chain disease
• primary amyloidosis
• Undetermined significance
• monoclonal gammopathy of undetermined
  significance (MGUS)
• Transient M protein
• viral infection
• post-valve replacement
• Malignacy
• bowel cancer, breast cancer
• Immune dysregulation
• AIDS, old age
• Chronic inflamation

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Monoclonal gammopathy of undetermined
significance ( MGUS)

• M protein presence, stable
• levels of M protein IgG lt 3,5g IgA lt 2g
  LClt1g/day
• normal immunoglobulins - normal levels
• marrow plasmacytosis lt 5
• complete blood count - normal
• no lytic bone lesions
• no signs of disease

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Monoclonal gammopathy of undetermined
significance ( MGUS)

• M protein
• 3 of people gt 70 years.
• 15 of people gt 90 years.
• MGUS is diagnosed in 67 of patients with an M
  protein.
• 10 of patients with MGUS develop multiple
  myeloma.

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