M y e l o m a
Definition
• Multiple myeloma is a malignant, clonal disorder of plasma cells which
originates in the bone marrow.
• Three key features are present:
1. A monoclonal proliferation of plasma cells
2. A monoclonal gammopathy
3. Decreased levels of other, normal (polyclonal) immunoglobulins.
Pathogenesis
• Myeloma originates in a stem cell which decides to differentiate along the B-
cell/plasma cell pathway.
• Cytokines (especially IL-6) induce differentiation and proliferation of the
malignant cells.
• Cytokines (released by the plasma cells) also mediate bone destruction, via
osteoclastic resorption.
Clinical Features
• Relatively common disorder (1% of all malignancies and 10% of all
hematologic malignancies in adults).
• Occurs in adults (rare <35 years old; highest incidence in 50s).
• Signs and symptoms:
• Bone pain (back, extremities) from lytic lesions
• Weakness
• Recurrent, persistent infections (big problem)
• Renal failure (multifactorial; due in large part to toxic effect of light chains
on tubular epithelium)
• Hypercalcemia (from bone resorption) can lead to neurologic changes and
contribute to renal disease.
Laboratory Findings
• Electrophoresis (ELP) shows monoclonal immunoglobulin spike (“M-
protein”, monoclonal gammopathy).
• Most common heavy chain expressed in myeloma is IgG; next are IgA and
IgD. IgE myeloma is extremely rare, and IgM myeloma is almost unheard of.
• Almost one-fifth of all cases of myeloma have plasma cells that secrete only
light chains (called Bence-Jones proteins). These light chains pass through
the kidney! Therefore, need to look at urine as well as serum ELPs.
• The total amount of immunoglobulin is increased (due to the large
monoclonal immunoglobulin spike), but the amount of normal (polyclonal)
immunoglobulin is decreased.
Morphologic Findings
Blood
• Anemia (normochromic, normocytic)
• Rouleaux!
• Rarely see circulating plasma cells.
Bone marrow
• Increased number of plasma cells (normal plasma cell number is <3%; in
myeloma, plasma cells usually number 20% or more), usually arranged in
big sheets.
• Plasma cells may look normal (“mature” type), slightly immature
(“intermediate” type), or barely recognizable as plasma cells
(“plasmablastic” type).
• Plasma cells may have unusual-looking inclusions: crystals, Chinese-letter-
like inclusions, Russell bodies (small, reddish cytoplasmic blobs), Dutcher
bodies (large, single, intranuclear pseudoinclusions that look like holes).
• Some patients have amyloidosis due to over-production of immunoglobulin
light chains (look in vessel walls for pink, smudgy material).
Treatment and Prognosis
• Chemotherapy may decrease symptoms, but does not prolong life.
• Bone marrow transplantation is the only hope for cure.
• Prognosis without bone marrow transplantation is poor (median survival = 3
years).
