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36 Cards in this Set
- Front
- Back
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Definition of plasma cell neoplasm?
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Neoplasm
Behavior may be benign or malignant Ig secreting cells (usually plasma cells) Monoclonal serum Ig |
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How are plasma cell neoplasms defined?
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DISTRIBUTION
1. plasmacytoma 2. multiple myeloma TISSUE INVOLVEMENT 1. bone 2. lymph node 3. extranodal sites CHARACT OF IMMUNOSECRETORY PROTEIN 1. IgM -- increased serum viscosity 2. Heavy chain only -- different clinical presentations 3. Amyloid production CHARACT OF MALIGNANT CELL 1. plasma cell 2. small lymphocyte 3. lymphyplamacytoid lymphocyte |
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List the plasma cell neoplasms
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1. Monoclonal gammopathy of Undetermined Significance (MGUS)
2. Plasmacytoma 3. Multiple Myeloma 4. Waldenstrom Macroblobulinemia 5. Primary Amyloidosis 6. Heavy Chain Disease |
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Monoclonal serum proteins?
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Often an incidental finding, partic in older pts
Each plasma cell produces a unique protein. Plasma cell neoplasms are due to increase in one MONOCLONAL protein -- produces a very narrow band on serum protein electrophoresis (SPEP), a spike -- identity of the monoclonal protein can be determined by Immunifixation Electrophoresis (IFE) -- all other Ig are decreased (fxnal hypogammaglobulinemia) **polyclonal gammopathy due to an increase in many different proteins is due to chronic infection or inflamm |
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Heavy vs. light chain production?
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There is usually a tight balance btwn heavy and light chain production
Plasma cell neoplasms may contain: -- excess light chains -- light chains only -- heavy chains only -- non-secretory plasma cells Free light chains can spill into urine and be identified by Urine Protein Electrophoresis (UPEP) -- referred to as Bence-Jones proteinuria |
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Plasma cell neoplasm Ig may be...
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abnormal in its physical properties and lead to amyloid deposition
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What symptoms might an excess of monoclonal proteins cause?
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Increase in serum viscosity is assoc w:
-- visual impairment -- dizziness -- deafness ** this is known as hyperviscosity syndrome Some proteins precipitate at low temperature --> cryoglobulinemia |
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Multiple myeloma pathogenesis?
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Tissue infiltration by plasma cells
-- multiple tumerous masses of neoplastic plasma cells throughout the skeletal system -- increased osteoclastic activity resulting from cytokines that increase bone resorption in areas infiltrated by plasma cells |
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Tissues infiltrated by multiple myeloma and consequences?
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Bone -- pain, pathologic fractures, lytic lesions, hypercalcemia
Bone Marrow -- anemia, leukopenia, thrombocytopenia Kidney -- renal failure Lymph nodes -- unusual c.f. Waldenstrom's Liver Spleen |
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Result of multiple myeloma monoclonal Ig?
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M spike
IgG > IgA > IgM > IgD > IgE Hypogammaglobulinemia -- decrease in other normal Ig Bence Jones proteins -- light chain spill-over into urine Amyloid -- lambda > kappa Hyperviscosity |
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Multiple myeloma and renal failure?
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Found in approx 1/5 patients at diagnosis.
Multiple causes: 1. proteinaceous casts -- usually Ig 2. Ig light chain deposition 3. amyloid 4. infilt by plasma cells 5. pyelonephritis -- neutropenia -- decresed fxn Ig 6. hypercalcemia -- bone destruction -- immobilization 7. hyperuricemia |
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Patients w/ light chain only disease may have normal...?
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SPEP because the protein is excreted in the urine.
Therefore, UPEP is req'd in pts being evaluated for plasma cell neoplasm |
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Multiple myeloma immune dysfxn?
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1. decreased fxnal, normal Ig
2. marrow infilt by plasma cells leads to neutropenia 3. cellular immunity is relatively unaffected **infection is major cause of death |
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Multiple myeloma clinical presentation?
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EPIDEMIOLOGY
-- median age 65yrs -- males > females -- African 2x Caucasian SYMPTOMS -- lytic lesions or compression fractures -- fatigue (anemia, hypercalcemia, renal failure -- infections -- 1/5 pts are asymptomatic and have incidental M-spike finding RADIOLOGIC STUDIES -- multiple lytic bone lesions (skeletal bone survey) |
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Multiple myeloma lab findings?
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1. Increased serum protein
-- SPEP reveals M-spike (>3g/dl) -- IFE characterized monoclonal protein 2. Hypercalcemia -- due to bone destruction and immobilization 3. Elevated BUN and Creatinine -- renal failure 4. Proteinuria -- monoclonal protein on UPEP (if light chain involved) |
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Multiple myeloma peripheral smear findings?
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1. anemia
-- marrow infilt -- decreased erythropoietin formation 2. rouleaux formation -- increased plasma protein 3. circulating plasma cells rare |
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Multiple myeloma histology of bone lesions and bone marrow?
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1. infiltration and replacement by plasma cells
-- usually greater than 30% of cells in BM 2. Plasma cells often look normal -- may have nucleoli and more finely distributed chromatin 3. Immunohistochem show monoclonal Ig |
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Multiple myeloma clinical course?
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POOR PROGNOSIS
1. w/o therapy: median survival 6mos 2. w/ chemo: median survival 3yrs Objective responses in half pts treated w/ Melphalan and Prednisone increased survival reported from autologous BM and PB stem cell transplants |
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Identification of a monoclonal spike is diagnostic of...?
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It can be seen in ANY plasma cell neoplasm
Is NOT diagnostic of only multiple myeloma Significance of M-spike depends on the presence of other features indicating another overt neoplasm |
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Definition of MGUS?
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Monoclonal Gammopathy of Undetermined Significance
1. monoclonal serum protein 2. monoclonal protein <3gm/dL 3. Bence Jones proteins ABSENT 4. Hypogammaglobilinemia ABSENT 5. lytic bone lesions ABSENT 6. BM plasma cells <10% |
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Clinical course of MGUS?
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No treatment is required
-- 1/4 develop overt plasma cell neoplasm -- 1/4 monoclonal protein increases, but does not reach criteria for myeloma -- 1/4 stable levels of monoclonal protein -- 1/4 die of other causes |
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Clinical presentation of Waldenstrom's Macroglobulinemia?
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weakness, fatigue, weight loss
lymphadenopathy hepatomegaly splenomegaly hyperviscosity syndrome -- visual impairment, headache, dizziness, deafness cryoglobulinemia -- Reynaud's phenomenon |
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Waldenstrom's Macroglobulinemia radiologic studies?
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NO lytic lesions
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Waldenstrom's Macroglobulinemia lab studies?
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Serum protein electrophoresis: M-spike
Immunofixation electrophoresis: IgM |
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Waldenstrom's Macroglobulinemia peripheral blood and bone marrow?
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1. circulating malignant cells and BM infiltration
-- lymphocytes -- lymphoplasmacytoid lymphocyte -- plasma cell 2. Anemia -- BM formation -- hemolytic anemia (autoimmune, cold agglutinins) |
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Waldenstrom's Macroglobulinemia lymph node histology?
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Resembles SLL
Infiltrate of: -- lymphocytes -- lymphoplasmacytoid lymphocytes -- plasma cells |
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Waldenstrom's Macroglobulinemia clinical course?
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median survival 4 yrs
symptoms alleviated by removal of protein (plasmaphoresis) |
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What is amyloid?
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A pathologic, proteinaceous substance deposited between cells with a varied chemical nature and uniform physical nature
Non-branching fibrils 7.5-10nm in diameter Beta-pleated sheet conformation |
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Chemical composition of amyloid?
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P component (5%)
Amyloid protein (95%) 1. AL - amyloid light chain derived protein (Ig) 2. AA - amyloid associated protein (acute phase reactant) 3. transthyretin (ATTR) 4. beta-2 microglobulin 5. beta-2 amyloid protein |
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Amyloidosis diagnosis?
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1. Gross: waxy, white
2. Morphology: amorphous, pink, hyaline extracellular material 3. Special stains: Congo red - gree birefringence 4. EM: non-branching fibrins, varying length, 7.5-10nm in diameter 5. Additional studies: SPEP, UPEP, BM exam |
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How do we classify amyloidosis?
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Classif based on:
1. composition of protein 2. systemic/localized 3. primary/secondary 4. acquired/inherited |
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Primary amyloidosis
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Related to underlying plasma cell neoplasm producing abnormal Ig (ex: multiple myeloma)
-- Abnormal light chains produce AL Some pts w/ monoclonal Ig producing plasma cells DO NOT have other manifest of myeloma (bone lesions, etc) --> referred to as primary amyloidosis This amyloidosis has systemic distribution |
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Reactive systemic amyloidosis
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Amyloid containing AA protein in pt's w/ underlying inflamm condition such as RA
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Hemodialysis associated amyloidosis
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beta-2 microglobulin
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Senile systemic amyloidosis
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usually involves the heart
restrictive cardiomyopathy and/or arrhythmia Normal transthyretin protein deposited c.f. Heredofamilial Amyloidosis |
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What is the clinical course of amyloidosis?
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That of the underlying disease
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