myeloma_06-07.ppt

Immunosecretory DisordersImmunosecretory Disorders

Masatoshi Kida, M.D.Dept. of Pathology

University of Vermont


• 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 myelomaB. plasma cell leukemiaC. non-secretory myelomaD. osteosclerotic myeloma (POEMS syndrome)E. solitary plasmacytoma of boneF. extramedullary plasmacytomaG. primary macroglobulinemia (lymphoplasmacytic lymphoma) (Waldenstrom’s macroglobulinemia)H. heavy-chain disease

Monoclonal Gammopathies of Monoclonal Gammopathies of Unknown Significance Unknown Significance

(“Benign” Monoclonal Gammopathies)(“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 & leukemiasb. other immune disorders

Multiple Myeloma Multiple Myeloma (Plasma Cell 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 Multiple Myeloma (Plasma Cell 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 Multiple Myeloma (Plasma Cell Myeloma) (Plasma Cell Myeloma)

genetic abnormalitygenetic abnormality

• deletion 13q• rearrangement 14q• balanced translocation t(4;14)(p6.3;q32)


clinical courseclinical course

• infection, renal failure, hemorrhage

• progressive course

• death within 2-5 yrs


Ig secretionIg secretion

52% Ig G

18% Ig A

11% Ig M

1% Ig D

rare Ig E

Variant Forms of “Myeloma”Variant Forms of “Myeloma”

A. smoldering multiple myelomaB. plasma cell leukemiaC. non-secretory myelomaD. osteosclerotic myelomaE. solitary plasmacytoma of boneF. extramedullary plasmacytomaG. primary macroglobulinemia (lymphoplasmacytic

lymphoma)H. heavy-chain disease

smoldering multiple myelomasmoldering multiple myeloma

• serum M-protein >3g/dL• >10% plasma cells in BM• no anemia, renal insufficiency or skeletal lesionClinical feature:• starting as “benign” monoclonal gammopathy• transforms into multiple myeloma

need to be closely observed over timeTreatment:• must not be treated unless progression occurs

plasma cell leukemiaplasma cell leukemia• >20% plasma cells in peripheral blood• absolute plasma cell count at least 2000/LClinical feature:1) primary (60%) : diagnosed in leukemic phase

• younger age• hepatosplenomegaly, lymphadenopathy• longer survival (median 6.8 mo)(vs 1.3 mo)

2) secondary (40%) : following previous MMTreatment:• generally unsatisfactory, but some response to melphalan and

prednisone• secondary plasma cell leukemia rarely responds to chemotherapy

non-secretory myelomanon-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 myelomaosteosclerotic myeloma(POEMS syndrome)(POEMS syndrome)

• Polyneuropathy, Organomegaly, Endocrionopathy, M-protein, Skin 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 bonesolitary plasmacytoma of bone

• solitary bone lesion (histologically similar to MM)(vertebrae, pelvis, femur, humerus)

• no M-protein in serum or urineClinical feature:• 50% alive at 10 yrs• 15 to 25% disease-free at 10 yrs• progression into MM within 3 to 4 yrsTreatment:• radiation therapy• no significant effect with chemotherapy

extramedullary plasmacytomaextramedullary plasmacytoma

• lesions outside BMClinical 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 MMTreatment:• 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 macroglobulinemiaprimary macroglobulinemia(Waldenstrom’s 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 macroglobulinemiaprimary macroglobulinemia(Waldenstrom’s macroglobulinemia)(Waldenstrom’s macroglobulinemia)

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myeloma_06-07.ppt