Multiple Myeloma

Multiple Myeloma
Dr. Shahzad Ali Jiskani

Assistant Professor
Department of Pathology
Chandka Medical College, SMBBMU
Introduction
 Malignant B cell lymphoproliferative disorder of the marrow with plasma

cells predominating.
 Most common primary malignancy of bone
 Function of plasma cells  Come from B cells and produce antibodies

(immunoglobulins)
 MM is characterized by excessive number of abnormal plasma cells in
bone marrow and overproduction of intact monoclonal immunoglobulin
(IgG, IgM, IgA, IgE, IgD) or Bence-Jones protein (free monoclonal
kappa/lambda light chains).
 Heavy chains
 IgG (60-70%)
 IgA
 IgM
 IgD
 IgE
 Light chains
 Kappa (κ)
 Lambda (λ)
Myeloma cells
produce
abnormal Overproduce monoclonal
immunoglobulins
protein or paraprotein
Ineffective immunoglobulins
Leads to decreased bone

marrow function
Destruction of bone tissue
 Common in 5th to 7th decade of life
 Males>females
 Risk factors:
 Age >60
 Exposure to pesticides
 Radiation
 Industry worker
 Exposure to benzene
Classification of Myeloma
Plasma
Cell
Monoclonal Gammopathy of
Dyscrasias Undetermined Significance (MGUS)
Asymptomatic Multiple Myeloma

(Smoldering/Indolent)
Symptomatic Multiple Myeloma

Pathophysiology
 Pathological and clinical features of myeloma are due to:
 Tissue infiltration
 Production of large amount of paraprotein
 Impairment of immunity
 Release of cytokines
 IL-6, RANK, TNF
 Angiogenesis
 VEGF
 Decreased immune response

Mechanism of Disease
 Plasma cell proliferation
 Anemia, bone marrow suppression, infection risk
 Osteoclasts
 Bony lesions, fractures, vertebral collapse, spinal cord compression
 Paraproteins and hypercarlcemia

 Renal failure
 Hypercalcemia
 Polyuria, thirst, drowsiness, coma
 Plasma cells produce proteins
called antibodies.
 Antibodies attach to foreign

substances to fight infection and
disease.
 In multiple myeloma, the body makes too many plasma cells (myeloma
cells).
 These cells produce antibodies that the body does not need.
Bence – Jones Proteins
 15-20% of patients with multiple myeloma produce incomplete

immunoglobulins, containing only the light chain portion of immunoglobulin
 Primarily in urine, rather than in blood (immunoelectrophoresis)
 Absent in non-secretory myeloma

Common sites of bone involvement
Clinical Manifestation
Bone pain Weight loss Anemia Thrombocytopenia
Renal failure Hypercalcemia Hyperviscosity Hyperuricemia
Infection
CRAB
Kidney Problems
Excess proteins in the blood
Filtered through kidneys
Kidney damage
Renal failure
Laboratory Investigations
 CBC
 Bone marrow biopsy
 Biochemistry – albumin, BUN, LDH, Ca, creatinine
 Serum β2 – macroglobulin
 Quantitative immunoglobulins
 Chromosomal analysis
 FISH
Paraprotein / M Protein
Microscopy
 Small, round blue cells with clock face

nuclei and abundant cytoplasm with
perinuclear clearing halo
Imaging
Diagnostic Criteria for Multiple
Myeloma
 Major Criteria
 Biopsy – proven plasmacytoma
 Bone marrow sample showing 10% plasma cells
 Elevated monoclonal immunoglobulin in blood or urine
 Minor criteria
 Bone marrow <10% plasma cells
 Minor monoclonal immunoglobulin levels in blood or urine
 Imaging – holes in bones due to tumor growth
 Low antibody levels in blood
Monoclonal Gammopathy of
Undetermined Significance (MGUS)
 Serum M protein <3g/dL
 Bone marrow plasma cells <10%
 Absence of anemia, renal failure, hypercalcemia and lytic lesions
 16% cases can transform to malignancy

Asymptomatic Multiple Myeloma
Smoldering MM Indolent MM
• Serum M protein >3g/dL or • Stable serum/urine M protein

BM plasma cells ≥10%
• BM plasmacytosis
• Absence of anemia, renal
failure, hypercalcemia and • Mild anemia or few small lytic
lytic lesions bone lesions
• Absence of symptoms
Non-secretory Myeloma
 No M-protein in serum/urine
 Bone marrow shows 10% plasma cells or plasmacytoma
 Myeloma-related organ or tissue impairment

Solitary Plasmacytoma of Bone
 No M-protein in serum/urine
 Single area of bone destruction due to clonal plasma cells
 Bone marrow not consistent with multiple myeloma
 Normal skeletal survey
 No related organ or tissue impairment

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Multiple Myeloma

Dr. Shahzad Ali Jiskani

 Malignant B cell lymphoproliferative disorder of the marrow with plasma

 Most common primary malignancy of bone

 Function of plasma cells  Come from B cells and produce antibodies

Leads to decreased bone

Asymptomatic Multiple Myeloma

Symptomatic Multiple Myeloma

 Production of large amount of paraprotein

 Decreased immune response

 Paraproteins and hypercarlcemia

 Antibodies attach to foreign

 15-20% of patients with multiple myeloma produce incomplete

 Primarily in urine, rather than in blood (immunoelectrophoresis)

 Absent in non-secretory myeloma

Bone pain Weight loss Anemia Thrombocytopenia

Renal failure Hypercalcemia Hyperviscosity Hyperuricemia

Excess proteins in the blood

Filtered through kidneys

 Bone marrow biopsy

 Biochemistry – albumin, BUN, LDH, Ca, creatinine

 Small, round blue cells with clock face

 Bone marrow plasma cells <10%

 Absence of anemia, renal failure, hypercalcemia and lytic lesions

 16% cases can transform to malignancy

• Serum M protein >3g/dL or • Stable serum/urine M protein

 Bone marrow shows 10% plasma cells or plasmacytoma

 Myeloma-related organ or tissue impairment

 Single area of bone destruction due to clonal plasma cells

 Bone marrow not consistent with multiple myeloma

 Normal skeletal survey

 No related organ or tissue impairment

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