! Multiple myeloma : as myeloma or
plasma cell myeloma
! cancer of the Plasma Cell
! Multiple myeloma
! excessive numbers of abnormal plasma
cells in the bone marrow
! overproduction of intact monoclonal
immunoglobulin (IgG, IgA, IgD, or IgE) or
Bence-Jones protein (free monoclonal κ
and λ light chains)
! Normal Plasma Cell Function in
the Immune System
! Stem cells can develop into B
lymphocytes -- >travel to the lymph
nodes, mature, and then travel
throughout the body.
! When foreign substances (antigens)
enter the body -- >B cells develop
into plasma cells that produce
immunoglobulins Ig (antibodies) to
help fight infection and disease.
Figure legend: In multiple myeloma, the B cell is damaged
and gives rise to too many plasma cells (myeloma cells).
These malignant cells do not function properly and
their increased numbers produce excess single type
immunoglobulins that the body does not need along
with reduced amounts of normal immunoglobulins.
! These myeloma cells travel through the
bloodstream and collect in the bone
marrow, where they cause permanent
damage to healthy tissue.
! As tumors grow, they invade the hard
outer part of the bone, the solid tissue.
! In most cases, the myeloma cells spread
into the cavities of all the large bones
of the body, forming multiple small
lesions. This is why the disease is known
as "multiple" myeloma.
! Multiple myeloma is the second most
prevalent blood cancer after nonHodgkin's lymphoma
! 1% of all cancers and 2% of all
! Age 60-65 years most common
! Occurs in men > women
! African Americans and Native Pacific
Islanders have the highest reported
incidence of this disease and Asians
! Genetic causes
! Ongoing research is investigating whether
HLA-Cw5 or HLA-Cw2 may play a role in the
pathogenesis of myeloma.
! Environmental or occupational causes
! significant exposures in the agriculture,
food, silicon ,Benzene, Nickel and
! Radiation has been linked to the
development of myeloma.
! In 109,000 survivors of the bombing of
Nagasaki, 29 died from myeloma from
1950-1976; however, some recent studies do
not confirm that these survivors have an
increased risk of developing myeloma.
! common tetrad of multiple
myeloma is CRAB
! Bone pain
! Myeloma bone disease -- >proliferation
of tumor cells and release of IL-6
<osteoclast activating factor :OAF>->stimulates osteoclast to break down
bone-- > leading to hypercalcemia
! These bone lesions in plain
radiographs-- > "punched-out" / lytic
! Bone pain
! Myeloma bone pain -- > involves the
rib ,sternum, spine , clavicle , skull ,
humerus & femur
! The lumbar vertebrae are one of the
most common sites of pain -- >may lead
to spinal cord compression.
! Persistent localized pain may indicate
a pathological fracture
! Pt. present with confusion, somnolence,
bone pain, constipation, nausea, and
! The anemia :normocytic and
! It results from the replacement of
normal bone marrow by infiltrating
tumor cells and inhibition of normal red
blood cell production (hematopoiesis) by
! bleeding resulting from thrombocytopenia.
! In some patients, monoclonal protein may
absorb clotting factors and lead to bleeding,
but this development is rare.
! Malignant plasma cells excretes an abnormal
M protein (Para-protein)
! high volume of monoclonal protein -- >
blood viscosity increases-- >complications
such as stroke, myocardial ischemia, or
! Organism : polysaccharide encapsulated
! Common pneumonia pathogens :S
pneumoniae, S aureus, and K pneumoniae
! Common pathogens causing
pyelonephritis : E coli and other gramnegative organisms.
! The increased risk of infection is due to
immune deficiency resulting from diffuse
hypogammaglobulinemia which is due to
decreased production and increased
destruction of normal antibodies.
! Renal failure
! Renal failure may develop both acutely
! It is commonly due to hypercalcemia.
! It may also be due to tubular damage from
excretion of light chains, which can
manifest as the Fanconi syndrome (type II
renal tubular acidosis).
! Other causes include glomerular
deposition of amyloid, hyperuricemia,
recurrent infections (pyelonephritis),
and local infiltration of tumor cells.
! Neurological symptoms
! Common problems are weakness, confusion
and fatigue due to hypercalcemia.
! Headache, visual changes and retinopathy
may be the result of hyperviscosity of the
blood depending on the properties of the
! Finally, there may be radicular pain, loss of
bowel or bladder control (due to
involvement of spinal cord leading to cord
compression) or carpal tunnel syndrome and
other neuropathies (due to infiltration of
peripheral nerves by amyloid).
! It may give rise to paraplegia in late
• Anemia ( normochrom )
• Rouleaux Formation
• Very High ESR (eg. 150 / 160 )
• Proteinuria (Bence Jones protein)
n Abnormal Electrophoresis protein
(monoclonal Spike on beta or gamma)
Protein Serum Electrophoresis
Monoclonal Protein in Myeloma
Kyle RA and Rajkumar SV. Cecil Textbook of Medicine, 22nd Edition, 2004
n Median survival : 3 yrs
n Worsen in : very high paraprotein spikes, renal
failure, hypercalsemia & extensive bone lessions
n High Tumor Burden :
spike IgG > 7 g/dl
hematocrite < 25 %
ca serum > 12 mg/dl
bone lession > 3 location
è median survival 1 yr
! Consider MM in elderly patients with new
onset bone pain/fatigue/CRAB symptoms not
resolving with treatment
! Basic work up: SPEP/UPEP (+/- immunofixation),
CBC, peripheral smear, BUN/CR, Ca, skeletal
DDx, MGUS, asymptomatic vs symptomatic,
Waldenstrom’s, Amyloidosis, NHL, etc..
! No Tx for MGUS and asymptomatic MM.
! Manage Complications: Bisphosphonates,
orthopedics referral PRN, Vaccination, CRAB.
SKDI revisi 2012
! MYELOMA MULTIPEL berada pada area
! Tingkat Kemampuan 1: mengenali dan menjelaskan
! Lulusan dokter mampu mengenali dan menjelaskan
gambaran klinik penyakit, dan mengetahui cara yang paling
tepat untuk mendapatkan informasi lebih lanjut mengenai
penyakit tersebut, selanjutnya menentukan rujukan yang
paling tepat bagi pasien.