Multiple Myeloma lecture Latest Test Exam
With Verified Solutions
Multiple Myeloma
B-cell malignancy of neoplastic plasma cells that produce a monoclonal immunoglobulin. Clone of
plasma cells proliferates in bone marrow.
Clinical findings in multiple myeloma
Skeletal destruction with osteolytic lesions, osteopenia or pathologic fractures, anemia,
hypercalcemia, renal insufficiency, and recurrent bacterial infections.
Multiple myeloma epidemiology
2nd most common hematologic cancer in US (10%), 14,000 cases anually, 1% of cancers, 2% of cancer
deaths. Mean age at diagnosis: 65-68, African-americans more than whites, men more common.
Etiology
Unknown cause, theories: chronic antigenic stimulation of plasma cell-->transformation, ionizing
radiation, nickel, dioxin, benzene, aromatic hydrocarbons, silicon.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
2% over 50, benign asymptomatic proliferation, plasma cell <10% of BM cells, premalignant condition,
25x greater risk of multiple myeloma- 1%/year.
Pathogenesis of mutliple myeloma
Fab fragment (Bence-Jones protein) found in urine. Malignant transformation is of only one plasma
cell-monoclonal peak. Neoplastic cells form sheets replace normal NM, myeloma cells produce
osteoclast-stimulating factors-cytokines destroy bone. Osteoblasts suppressed-->demineralization
and bone destruction. Secondary hypercalcemia. IL-6 protects from apoptosis. Acquired cytogenic
alterations in 80%, loss of Chr13 long arm, chr14 prognostic implication.
Clinical picture of Multiple Myeloma
Bone pain (back or chest, less extremity) 60%, pain in movement, not at night, height reduced by
vertebral collapse. 80% of patients show abnormal radiograph. Focal osteolytic lesions (high
osteoblasts, low osteoclasts) 60%, osteoporosis, pathologic fractures, compression fractures of the
spine 20%, weakness and fatigue (32%), anemia, fever (<1%), bleeding uncommon, weight loss 24%,
complications: hypercalcemia, renal insufficiency, amyloidosis.
Physical findings of MM
Pallor; palpable, hepatomegaly, splenomegaly, lymphadenopathy-rare. Extramedullary
plasmacytoma: large, purplish, subcutaneous masses late.
Neurologic disease
Spinal cord compression from extramedullary plasmacytoma or bone fragment from vertebral body
fracture 5%, severe back pain with weakness/paresthesias of lower extremities, bladder/bowel
dyfunction/incontinence: medical emergency, test with MRI or CT myelography of entire spine.
Followup with treatment. Peripheral neuropathy uncommon/amyloidosis.
Infections with multiple myeloma
, Increased infection incidence, pneumococcus and gram negatives. From Ab response impairment,
normal plasma function by hypogammaglobulinemia and chemo (neutropenia and corticosteroids).
Renal disease
Serum creatinine increased in 50% and over 2 in 20%. May be presenting manifestation of MM. Cast
nephropathy (myeloma kidney) and hypercalcemia. Other types: AL-primary amyloidosis (amyloid
fibrils-fragments of monoclonal light chains, acute renal failure after radiocontrast administration,
proximal tubular dysfunction and Fanconi syndrome signs.
Fanconi syndrome
Proximal renal tubular acidosis, aminoaciduria, hypouricemia, and phosphate wasting. Releasting
substances into proximal tubules that should be reabsorbed into blood.
Myeloma cast nephropathy
Large, waxy, laminated casts in distal and collecting tubules. Mainly composed of precipitated
monoclonal light chains. Urine dipstick negative for protein usually.
Lab findings
Normocytic, normochromic anemia (Hb12) in 73-97%. Rouleaux formation (stacked erythrocytes)
found in more than half of patients. ESR >20mm/h in 84% and >100 in 1/3. Leukopenia (20%) and
thrombocytopenia (<100,000/uL-5%). Plasmacytosis in peripheral smear infrequent. Plasma cell
leukemia in 1.5%.
Monoclonal proteins
Most important diagnostic finding. Demonstration of monoclonal (M) protein in serum/urine. 97% of
patients.
Which immunoglobulin is increased in MM?
IgG (51.5%), IgA (21%), light chain (Bence Jones-16%), IgD (2%), IgM (0.5%-IgM melanoma). 7% have
no monoclonal protein. Kappa mosre common than lambda (2/1) except IgD melanoma. Level of
major uninvolved Igs (IgM and IgA) reduced in 91% patients overall, both in 73%.
Nonsecretory melanoma
Patients that have no M-protein in serum or urine on immunofixation at time of diagnosis. Renal
failure uncommon. survival not different. Detection by concentrations of monoclonal serum FLC
assay. More sensitive for detection of monoclonal FLC than urine, 19/28 reclassified as LCM.
Light Chain Melanoma
20% classified by light chain only in serum/urine, lack HC expression. Higher incidence of renal failures
(serum creatinine 2mg/dL in 1/3).
Laboratory artifacts
Circulating monoclonal protein can interfere with other lab tests on liquid-based analyzers by
precipitating or specific binding. Low HDL, high bilirubin, altered inorganic phosphate,
psuedohyponatremia.
Bone marrow examination in MM
With Verified Solutions
Multiple Myeloma
B-cell malignancy of neoplastic plasma cells that produce a monoclonal immunoglobulin. Clone of
plasma cells proliferates in bone marrow.
Clinical findings in multiple myeloma
Skeletal destruction with osteolytic lesions, osteopenia or pathologic fractures, anemia,
hypercalcemia, renal insufficiency, and recurrent bacterial infections.
Multiple myeloma epidemiology
2nd most common hematologic cancer in US (10%), 14,000 cases anually, 1% of cancers, 2% of cancer
deaths. Mean age at diagnosis: 65-68, African-americans more than whites, men more common.
Etiology
Unknown cause, theories: chronic antigenic stimulation of plasma cell-->transformation, ionizing
radiation, nickel, dioxin, benzene, aromatic hydrocarbons, silicon.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
2% over 50, benign asymptomatic proliferation, plasma cell <10% of BM cells, premalignant condition,
25x greater risk of multiple myeloma- 1%/year.
Pathogenesis of mutliple myeloma
Fab fragment (Bence-Jones protein) found in urine. Malignant transformation is of only one plasma
cell-monoclonal peak. Neoplastic cells form sheets replace normal NM, myeloma cells produce
osteoclast-stimulating factors-cytokines destroy bone. Osteoblasts suppressed-->demineralization
and bone destruction. Secondary hypercalcemia. IL-6 protects from apoptosis. Acquired cytogenic
alterations in 80%, loss of Chr13 long arm, chr14 prognostic implication.
Clinical picture of Multiple Myeloma
Bone pain (back or chest, less extremity) 60%, pain in movement, not at night, height reduced by
vertebral collapse. 80% of patients show abnormal radiograph. Focal osteolytic lesions (high
osteoblasts, low osteoclasts) 60%, osteoporosis, pathologic fractures, compression fractures of the
spine 20%, weakness and fatigue (32%), anemia, fever (<1%), bleeding uncommon, weight loss 24%,
complications: hypercalcemia, renal insufficiency, amyloidosis.
Physical findings of MM
Pallor; palpable, hepatomegaly, splenomegaly, lymphadenopathy-rare. Extramedullary
plasmacytoma: large, purplish, subcutaneous masses late.
Neurologic disease
Spinal cord compression from extramedullary plasmacytoma or bone fragment from vertebral body
fracture 5%, severe back pain with weakness/paresthesias of lower extremities, bladder/bowel
dyfunction/incontinence: medical emergency, test with MRI or CT myelography of entire spine.
Followup with treatment. Peripheral neuropathy uncommon/amyloidosis.
Infections with multiple myeloma
, Increased infection incidence, pneumococcus and gram negatives. From Ab response impairment,
normal plasma function by hypogammaglobulinemia and chemo (neutropenia and corticosteroids).
Renal disease
Serum creatinine increased in 50% and over 2 in 20%. May be presenting manifestation of MM. Cast
nephropathy (myeloma kidney) and hypercalcemia. Other types: AL-primary amyloidosis (amyloid
fibrils-fragments of monoclonal light chains, acute renal failure after radiocontrast administration,
proximal tubular dysfunction and Fanconi syndrome signs.
Fanconi syndrome
Proximal renal tubular acidosis, aminoaciduria, hypouricemia, and phosphate wasting. Releasting
substances into proximal tubules that should be reabsorbed into blood.
Myeloma cast nephropathy
Large, waxy, laminated casts in distal and collecting tubules. Mainly composed of precipitated
monoclonal light chains. Urine dipstick negative for protein usually.
Lab findings
Normocytic, normochromic anemia (Hb12) in 73-97%. Rouleaux formation (stacked erythrocytes)
found in more than half of patients. ESR >20mm/h in 84% and >100 in 1/3. Leukopenia (20%) and
thrombocytopenia (<100,000/uL-5%). Plasmacytosis in peripheral smear infrequent. Plasma cell
leukemia in 1.5%.
Monoclonal proteins
Most important diagnostic finding. Demonstration of monoclonal (M) protein in serum/urine. 97% of
patients.
Which immunoglobulin is increased in MM?
IgG (51.5%), IgA (21%), light chain (Bence Jones-16%), IgD (2%), IgM (0.5%-IgM melanoma). 7% have
no monoclonal protein. Kappa mosre common than lambda (2/1) except IgD melanoma. Level of
major uninvolved Igs (IgM and IgA) reduced in 91% patients overall, both in 73%.
Nonsecretory melanoma
Patients that have no M-protein in serum or urine on immunofixation at time of diagnosis. Renal
failure uncommon. survival not different. Detection by concentrations of monoclonal serum FLC
assay. More sensitive for detection of monoclonal FLC than urine, 19/28 reclassified as LCM.
Light Chain Melanoma
20% classified by light chain only in serum/urine, lack HC expression. Higher incidence of renal failures
(serum creatinine 2mg/dL in 1/3).
Laboratory artifacts
Circulating monoclonal protein can interfere with other lab tests on liquid-based analyzers by
precipitating or specific binding. Low HDL, high bilirubin, altered inorganic phosphate,
psuedohyponatremia.
Bone marrow examination in MM
