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36 Cards in this Set

  • Front
  • Back
Definition of plasma cell neoplasm?
Behavior may be benign or malignant
Ig secreting cells (usually plasma cells)
Monoclonal serum Ig
How are plasma cell neoplasms defined?
1. plasmacytoma
2. multiple myeloma

1. bone
2. lymph node
3. extranodal sites

1. IgM
-- increased serum viscosity
2. Heavy chain only
-- different clinical presentations
3. Amyloid production

1. plasma cell
2. small lymphocyte
3. lymphyplamacytoid lymphocyte
List the plasma cell neoplasms
1. Monoclonal gammopathy of Undetermined Significance (MGUS)
2. Plasmacytoma
3. Multiple Myeloma
4. Waldenstrom Macroblobulinemia
5. Primary Amyloidosis
6. Heavy Chain Disease
Monoclonal serum proteins?
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
Heavy vs. light chain production?
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
Plasma cell neoplasm Ig may be...
abnormal in its physical properties and lead to amyloid deposition
What symptoms might an excess of monoclonal proteins cause?
Increase in serum viscosity is assoc w:
-- visual impairment
-- dizziness
-- deafness
** this is known as hyperviscosity syndrome

Some proteins precipitate at low temperature --> cryoglobulinemia
Multiple myeloma pathogenesis?
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
Tissues infiltrated by multiple myeloma and consequences?
Bone -- pain, pathologic fractures, lytic lesions, hypercalcemia

Bone Marrow -- anemia, leukopenia, thrombocytopenia

Kidney -- renal failure

Lymph nodes -- unusual c.f. Waldenstrom's


Result of multiple myeloma monoclonal Ig?
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

Multiple myeloma and renal failure?
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
Patients w/ light chain only disease may have normal...?
SPEP because the protein is excreted in the urine.

Therefore, UPEP is req'd in pts being evaluated for plasma cell neoplasm
Multiple myeloma immune dysfxn?
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
Multiple myeloma clinical presentation?
-- median age 65yrs
-- males > females
-- African 2x Caucasian

-- lytic lesions or compression fractures
-- fatigue (anemia, hypercalcemia, renal failure
-- infections
-- 1/5 pts are asymptomatic and have incidental M-spike finding

-- multiple lytic bone lesions (skeletal bone survey)
Multiple myeloma lab findings?
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)
Multiple myeloma peripheral smear findings?
1. anemia
-- marrow infilt
-- decreased erythropoietin formation

2. rouleaux formation
-- increased plasma protein

3. circulating plasma cells rare
Multiple myeloma histology of bone lesions and bone marrow?
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
Multiple myeloma clinical course?
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
Identification of a monoclonal spike is diagnostic of...?
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
Definition of MGUS?
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%
Clinical course of MGUS?
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
Clinical presentation of Waldenstrom's Macroglobulinemia?
weakness, fatigue, weight loss
hyperviscosity syndrome
-- visual impairment, headache, dizziness, deafness
-- Reynaud's phenomenon
Waldenstrom's Macroglobulinemia radiologic studies?
NO lytic lesions
Waldenstrom's Macroglobulinemia lab studies?
Serum protein electrophoresis: M-spike

Immunofixation electrophoresis: IgM
Waldenstrom's Macroglobulinemia peripheral blood and bone marrow?
1. circulating malignant cells and BM infiltration
-- lymphocytes
-- lymphoplasmacytoid lymphocyte
-- plasma cell

2. Anemia
-- BM formation
-- hemolytic anemia (autoimmune, cold agglutinins)
Waldenstrom's Macroglobulinemia lymph node histology?
Resembles SLL

Infiltrate of:
-- lymphocytes
-- lymphoplasmacytoid lymphocytes
-- plasma cells
Waldenstrom's Macroglobulinemia clinical course?
median survival 4 yrs

symptoms alleviated by removal of protein (plasmaphoresis)
What is amyloid?
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
Chemical composition of amyloid?
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
Amyloidosis diagnosis?
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
How do we classify amyloidosis?
Classif based on:
1. composition of protein
2. systemic/localized
3. primary/secondary
4. acquired/inherited
Primary amyloidosis
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
Reactive systemic amyloidosis
Amyloid containing AA protein in pt's w/ underlying inflamm condition such as RA
Hemodialysis associated amyloidosis
beta-2 microglobulin
Senile systemic amyloidosis
usually involves the heart

restrictive cardiomyopathy and/or arrhythmia

Normal transthyretin protein deposited c.f. Heredofamilial Amyloidosis
What is the clinical course of amyloidosis?
That of the underlying disease