myeloma_06-07.ppt

Immunosecretory Disorders Masatoshi Kida, M.D. Dept. of Pathology University of Vermont

Immunosecretory Disorders
tend to occur in middle aged to elderly people
monoclonal proliferation of B-cells

secretion of Ig or portions of Ig (paraproteins, M component)

The amount of paraprotein produced is roughly proportional to the size of the proliferating cells

secretion of Ig or portions of Ig (paraproteins, M component)
generally behave in a malignant fashion

I. Monoclonal Gammopathies of Unknown Significance
(“Benign” Monoclonal Gammopathies)
II. Multiple Myeloma (Plasma Cell Myeloma)
III. Variant Forms of “Myeloma”
A. smoldering multiple myeloma
B. plasma cell leukemia
C. non-secretory myeloma
D. osteosclerotic myeloma (POEMS syndrome)
E. solitary plasmacytoma of bone
F. extramedullary plasmacytoma
G. primary macroglobulinemia (lymphoplasmacytic lymphoma)
(Waldenstrom’s macroglobulinemia)
H. heavy-chain disease

Monoclonal Gammopathies of Unknown Significance (“Benign” Monoclonal Gammopathies)
presence of M protein in asymptomatic individual
1-2% of adults over 30 y/o (usually over 50 y/o)
90% are of IgG
stable for >3 yr
BM: plasma cells are <15% of all cells
~20% evolves into overt myeloma in 10-15 yr
occasionally associated with a. carcinomas, lymphomas & leukemias b. other immune disorders

Multiple Myeloma (Plasma Cell Myeloma)
most common form of plasma cell malignancy
extensively involves BM
middle aged to elderly male
Sx: bone pain osteolytic lesions fractures severe osteoporosis (osteoclast activating factor)
most common primary bone tumor in adult

Multiple Myeloma (Plasma Cell Myeloma)
most common form of plasma cell malignancy
extensively involves BM
middle aged to elderly male
Sx: bone pain osteolytic lesions fractures severe osteoporosis (osteoclast activating factor)
monoclonal protein spikes
Bence-Jones proteins (Ig light chains) in the urine
plasmacytosis/multiple plasma cell aggregates

Multiple Myeloma (Plasma Cell Myeloma) genetic abnormality
deletion 13q
rearrangement 14q
balanced translocation t(4;14)(p6.3;q32)

Multiple Myeloma (Plasma Cell Myeloma) clinical course
infection, renal failure, hemorrhage
progressive course
death within 2-5 yrs

Multiple Myeloma (Plasma Cell Myeloma) Ig secretion
52% Ig G
18% Ig A
11% Ig M
1% Ig D
rare Ig E

Variant Forms of “Myeloma”
smoldering multiple myeloma
plasma cell leukemia
non-secretory myeloma
osteosclerotic myeloma
solitary plasmacytoma of bone
extramedullary plasmacytoma
primary macroglobulinemia (lymphoplasmacytic lymphoma)
heavy-chain disease

smoldering multiple myeloma
serum M-protein >3g/dL
>10% plasma cells in BM
no anemia, renal insufficiency or skeletal lesion
Clinical feature:
starting as “benign” monoclonal gammopathy
transforms into multiple myeloma need to be closely observed over time
Treatment:
must not be treated unless progression occurs

plasma cell leukemia
>20% plasma cells in peripheral blood
absolute plasma cell count at least 2000/  L
Clinical feature:
primary (60%) : diagnosed in leukemic phase
younger age
hepatosplenomegaly, lymphadenopathy
longer survival (median 6.8 mo)(vs 1.3 mo)
secondary (40%) : following previous MM
Treatment:
generally unsatisfactory, but some response to melphalan and prednisone
secondary plasma cell leukemia rarely responds to chemotherapy

non-secretory myeloma
no M-protein in serum or urine
account for 1 to 2% of myeloma
less renal involvement
Treatment:
similar response to chemotherapy as “secretory” myeloma

osteosclerotic myeloma (POEMS syndrome)
P olyneuropathy, O rganomegaly, E ndocrionopathy, M -protein, S kin change
Clinical feature:
chronic inflammatory-demyelinating polyneuropathy with motor disability
sclerotic skeletal lesions
hepatomegaly (~50%)
Treatment:
radiation for localized lesion
chemotherapy (melphalan and prednisone)

solitary plasmacytoma of bone
solitary bone lesion (histologically similar to MM) (vertebrae, pelvis, femur, humerus)
no M-protein in serum or urine
Clinical feature:
50% alive at 10 yrs
15 to 25% disease-free at 10 yrs
progression into MM within 3 to 4 yrs
Treatment:
radiation therapy
no significant effect with chemotherapy

extramedullary plasmacytoma
lesions outside BM
Clinical feature:
upper respiratory tract involvement (~80%) (nasal cavity, sinuses, nasopharynx, larynx)
may also seen in GI tract, CNS, U bladder, thyroid, breast, testes, parotid gland, lymph nodes
may be solitary, may metastasize
rarely transforms into MM
Treatment:
radiation therapy

caused by uncontrolled proliferation of lymphocytes and plasma cells (hybrid of lymphoplasmacytic lymphoma/leukemia and multiple myeloma) (lymphoplasmacytic lymphoma)
Clinical feature:
age : ~65 yrs, 60% male
normocytic, normochromic anemia (moderate to severe)
weakness, fatigue, bleeding (oozing from oronasal area), pallor, hepatosplenomegaly, lymphadenopathy, sensorimotor peripheral neuropathy
no destructive skeletal lesions
hyperviscosity syndrome (retinal hemorrhage, transient paresis, mental confusion, CHF, bleeding)
primary macroglobulinemia (Waldenstrom’s macroglobulinemia)

Treatment:
should not be treated unless symptomatic
chemotherapy (chlorambucil)
RBC transfusion (for anemia)
plasmapheresis (for hyperviscosity)
Prognosis:
median survival : 5 yrs
primary macroglobulinemia (Waldenstrom’s macroglobulinemia)

myeloma_06-07.ppt

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myeloma_06-07.ppt

by DominicDR

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