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Path - Plasma cell neoplasms + related disorders (ii) 1) Multiple Myeloma
Path - Plasma cell neoplasms + related disorders (ii) 1) Multiple Myeloma
Multifocal (many sites) BM disease - malignant prolif of plasma cells into neoplastic myeloma cells - skeletal destruction
bind to BM stromal cells via cell surface adhesion molecules
migrate to BM milieu (environment)
survival, growth, drug resistance
Monoclonal: 1 type of Ig made
intact
present in plasma nearly always
non-secretory myeloma v rare (<1% of cases)
unless light chain only
excreted in urine as Bence-Jones proteins
deposits, accumulates + blocks renal tubules (AL amyloidosis)
cytotoxic to renal rubular epethlium (myeloma kidney)
high MW
not present in urine unless patient has glomerular disease
IgG 55% of cases
IgA 25% of cases
rarely D/E/M
accounts for 15% of blood cancers
most common primary bone cancer
most common overall bone cancer = mets
typically in 50+ y/o
x3 more common in males
x2 more common in Africans compared to Caucasians
Pathogenesis
radiation
exposure to asbestos
petroleum products
rubber
plastic products
HHV
no known molecular pathologies (unlike lymphomas)
Myeloma cells make CKs + GFs
e.g. IL6 (osteoclast activating factor)
self-signalling
stims further myeloid cell growth + prolif
interact with stromal cells
activate osteoclasts via RANK Rs
inactivate osteoblasts
promote angiogenesis
Dx
radiology
skeletal lesions
multifocal
common in axial skeleton
vertebrae
ribs
skull
pelvis
femur
clavicle
scap
destructive, lytic
well-defined punched out soap bubble appearance
infiltrating tumour cells
BM exam
aspirate
trephine
increased plasma cells
often atypical (bi/tri/multinucleated)
perinuclear clearing/halo
eccentric/peripheral nucleus
immature blasts
Ig inclusions
Russell bodies = intracytoplasmic
Dutcher bodies = intranuclear
serum + urine electrophoresis
monoclonal (M) globulin spike
proteinuria from light chain
-ve serum + urine does not exclude MM
Ig levels
immunostaining
pink lobules inside cytoplasm
only 1 will be high
blood smear
low RBC charge + high Ig (hence high ESR)
rouleaux formation (stalks/aggregations)
Clinical features
CRAB
hypercalceamia
due to bone destruction
confusion
weakness
lethargy
abdo pain
constipation
polyuria
depression
renal stones
renal failure
in 50% of patients
2nd most common cause of death
due to
Bence-Jones proteins
AL amyloidosis
light chain deposition disease (occlusion)
hypercalceamia
hyperuricaemia (high uric acid due to increased cell destruction)
pyelonephritis
drug-induced (chemo)
anaemia
normocytic normochromic ("of chronic disease")
3 reasons why
1) BM failure
2) CKs inhibit RBC production
3) low erythropoietin due to renal failure
bone lesions
pain esp in lumbar vertebrae (cord compression)
pathological fractures
diffuse osteoporosis
tumour cell completely replaces BM (site of haemopoeisis)
pancytopenia (anaemia, leukopenia, throbocytopenia)