Hematology

year 2

Multiple myeloma
 ‫‪Hematology, Myeloma‬‬
‫أالستاذ الدكتور محمد شنين علي العبادي‬
‫بكلوريوس بالطب والجراحة العامة‪/‬كلية الطب‪-‬جامعة النهرين‬
‫شهادة البورد العراقي بامراض الدم‬
‫استشاري بامراض الدم‬
‫معاون عميد كلية الطب للشؤون العلمية‪/‬جامعة كربالء‬
 Multiple myeloma

Multiple myeloma represents malignant

neoplastic proliferation of B-lymphocytes within
the bone marrow, lymph nodes or the spleen
which will give rise to monoclonal plasma cells
which infiltrate the bone marrow.

Myeloma is extremely rare in people aged less

than 40 years.
‫لالطالع فقط وغير مطلوب كأهداف للمحاضرة‬
Multiple myeloma should be suspected in
anyone aged over 40 years with unexplained
bone pain or fractures, osteoporosis, osteolytic
lesions, anaemia with raised erythrocyte
sedimentation rate or raised plasma viscosity,
hypercalcaemia, renal impairment, proteinuria,
or recurrent infection.
 Three features of myeloma
Myeloma is characterized by the triad of bone
marrow plasmacytosis, lytic bone lesions on
skeletal radiology, and the presence of M
protein in the serum or urine or both.

Not all patients have all these features

 Pathogenesis, 1

1. Myeloma cell (monoclonal plasma cell) neoplastic

proliferation
Myeloma cells (monoclonal plasma cells) are
proliferating within the bone marrow leading to
early anaemia through suppression of
eryhtropoiesis and in advanced disease
leukopenia and thrombocytopenia due to
suppression of myelopoiesis and
megakariopoiesis.
 Pathogenesis, 2

2. Myeloma cell secretion of immunoglobulins.

Myeloma cells (monoclonal plasma cells) secrete
myeloma protein (M protein)which is monoclonal protein
in form of IgG paraprotein , IgA, free immunoglobulin
light chains, or rarely IgM together with suppression of
production of normal immunoglobulins with subsequent
liability for infections.
Free light chains are detectable in urine as Bence Jones
proteins. Accumulation of M protein may lead to
hyperviscosity especially IgA and IgM due to the large size
of immunoglobulin molecule. Deposition of the protein in
renal tubules resulting in renal failure.
 Pathogenesis, 3

3. Myeloma cells (monoclonal plasma cells) are

destructing the bones
Myeloma cells (monoclonal plasma cells) destroy
the bone since myeloma is associated with
increased osteoclastic bone resorption and
inhibition of osteoblastic bone formation. This
finding is characteristic for patients with multiple
myeloma which causes moderate or severe bone
pain especially back pain. Such bone destruction
results in characteristic osteolytic lesions
predisposing to pathological fractures.
Bone marrow infiltration by Plasma
cells in multiple myeloma
 Paraproteinemia
Paraproteinemia is defined as the presence of
paraprotein in blood or urine or both.
Paraprotein means monoclonal immunoglobulin
(Other names: monoclonal protein, M protein,
monoclonal spike) secreted by monoclonal
plasma cells.
‫لالطالع فقط وغير مطلوب كأهداف للمحاضرة‬
• Conditions associated with M proteins :
• A. Stable production
• 1. Monoclonal gammopathy of undetermined significance (MGUS).
• 2. Smouldering multiple myeloma.
• B. Progressive production
• 1. Multiple myeloma (IgG, IgA, free light chains, IgD, IgE,
• non-secretory, IgM).
• 2. Plasma cell leukemia.
• 3. Solitary plasmacytoma of bone.
• 4. Extramedullary plasmacytoma.
• 5. Waldenström’s macroglobulinaemia (IgM).
• 6. Chronic lymphocytic leukemia.
• 7. Malignant lymphoma.
• 8. Primary amyloidosis.
• 9. Heavy chain disease.
Diagnostic tests for multiple myeloma

1. Bone marrow aspirate: to identify plasma cell

infiltration (plasmacytosis). Such infiltration is absent in
rare cases in which there is plasmocytoma on bone
marrow biopsy.
2. Skeletal survey: to identify lytic bone lesions which are
not already detected. Magnetic resonance imaging
(MRI) is the most sensitive imaging technique for
myeloma and is valuable in suspected cord compression
but it is not routine for all patients.
3. Paraprotein typing and quantification by serum protein
electrophoresis
Serum protein electrophoresis shows normal representation
of albumin and globulins (α, β and γ).
Serum protein electrophoresis shows M-band (red arrow)
in multiple myeloma.
‫لالطالع فقط وغير مطلوب كأهداف للمحاضرة‬
• Diagnosis of multiple myeloma
• Diagnosis of multiple myeloma requires one major and one minor criteria
or it can be established by only 3 minor criteria
• Major criteria
• 1. Plasmacytoma on tissue biopsy.
• 2. Bone marrow plasmacytosis of >30%
• 3. The presence of M protein band: IgG>3.5 g/l; IgA>2.0 g/l
• 4. Urinary Kappa or Lambda chain excretion of > 1g/24 hours with no
amyloidosis.
• Minor criteria
• 1. Bone marrow plasmacytosisof 10-30%
• 2. Lytic bone lesions
• 3. The presence of monoclonal proteins (less than that of major criteria)
• 4. Decreased normal immunoglobulins: IgM<500 mg/l; IgA < 1.0 g/l or IgG
< 6.0 g/l.
Thank you