myeloma_06-07.ppt
Upcoming SlideShare
Loading in...5
×

Like this? Share it with your network

Share
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
1,826
On Slideshare
1,826
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
46
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. Immunosecretory Disorders Masatoshi Kida, M.D. Dept. of Pathology University of Vermont
  • 2. Immunosecretory Disorders
    • tend to occur in middle aged to elderly people
    • monoclonal proliferation of B-cells
  • 3. 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)
  • 4. The amount of paraprotein produced is roughly proportional to the size of the proliferating cells
  • 5. 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)
    • generally behave in a malignant fashion
  • 6. Immunosecretory Disorders
    • 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
  • 7. 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
  • 8. 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
  • 9. 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
  • 10. Multiple Myeloma (Plasma Cell Myeloma) genetic abnormality
      • deletion 13q
      • rearrangement 14q
      • balanced translocation t(4;14)(p6.3;q32)
  • 11. Multiple Myeloma (Plasma Cell Myeloma) clinical course
    • infection, renal failure, hemorrhage
    • progressive course
    • death within 2-5 yrs
  • 12. Multiple Myeloma (Plasma Cell Myeloma) Ig secretion
    • 52% Ig G
    • 18% Ig A
    • 11% Ig M
    • 1% Ig D
    • rare Ig E
  • 13. 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
  • 14. 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
  • 15. 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
  • 16. 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
  • 17. 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)
  • 18. 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
  • 19. 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
  • 20.
    • 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)
  • 21.
    • 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)
  • 22.  
  • 23.