3.26.14* Plasma Cell Neoplasms Flashcards
PPT* Lecture Notes* Reading (Chapter 21)* Pictures
paraproteinaemia
presence of monoclonal immunoglobulin band (M-protein) in the serum, from a single clone of plasma cells.
multiple myeloma
a. clinical presentaiton: caused by plasma cell accumulation in the bone marrow, the presence of m-protein in serum and/or urine. Most over 40, peak at 70. Can progress to tissue damage. Often bone pain due to fractures, anemia, recurrent infections (due to deficient Ab production and neutropenia), low Ab (immune paresis)
b. origin- post-germinal center plasma cell and migrate to bone marrow.
c. diagnostic test: CD138, serum free light chain ratio. Bence-Jones protein in the urine (66%). High ESR.
d. PBS: Rouleaux formations
What kinds of tissue damage can arise from myltiple myeloma
C- hypercalcemia
Renal impairment
Anemia
bBone disease
Immunophenotype of plasma cells
CD138
What types of m-proteins are released in multiple myeloma
IgG (60%)
IgA (20%)
light chains (20%) only
(but almost all malignant plasma cells release light chains)
What causes bone lesions in multiple myeloma?
The osteolytic lesions are caused by osteoclast activation resulting from high serum levels of RANKL (receptor activator of nuclear factor-κB (NF-κB) ligand), produced by plasma cells and bone marrow stroma, which binds to activatory RANK receptors on the osteoclast surface.
Monoclonal gammopathy of undetermined significance
serum paraprotein may be sometimes be detected without any evidence of myeloma or other underlying disease. over 50 and increasingly common with age. No clinical symptoms and plasma cell numbers are normal (4%) or slightly raised (10%).
myeloma is
terminally differentiated B cell malignancy (monoclonal)
What markers will give a bad prognosis in multiple myeloma
17p deletions
what treatment is best for multiple myeloma
autologous stem cell transplant
What is the best way to diagnose amyloidosis?
peripheral fat biopsy to check small vessels for amyloid deposits
*What is an M spike?
seen in serum electrophoresis, meaning presence of monoclonal proteins.
(A broad diffuse band for one globulin protein would mean a polyclonal protein).
*What does an IFE tell you?
(immunofixation electrophoresis)
if there is a monoclonal population and what Ab/chain it is.
*Name the four components of CRAB
calcium (hypercalcemia)
renal deficiency
anemia
bone lesions
*Describe the mechanism of bone destruction in myeloma.
plasma cells in BM secrete cytokines (DKK1) which leads to increase in serum RANKL that activates osteoclasts to break down bone.
*Stage a myeloma with Durie Salmon and ISS.
Durie Salmon staging of MM
1: low M protein, normal calcium, normal bone
2: intermediate
3: CRAB, high M protein
ISS staging of MM
1: B2M less than 3.5 and albumin >3.5
2: both B2M and albumin 3.5 and lytic lesions
*Name the worst prognostic chromosome abnormality in Myeloma.
17p deletion (p53)
(others:
high B2M, bone lesions, renal insufficiency by creatinine, high LDH/CRP due to cell turnover)
*What two classifications of new drugs have changed the way we treat myeloma? Mechanism of action?
a. IMIDs: cut off stromal support leading to myeloma cell death
b. BORTEZOMIB- proteosome inhibitors: prevents myeloma cells by degrading pro-apoptotic factors, permitting apoptosis.
*When is an autologous transplant indicated in myeloma?
.
*Why do Waldenstrom patients become hyperviscous more commonly than myeloma patients?
.
*Name three causes of amyloidosis.
a. light chain amyloidosis (myeloma or non-myeloma) involves nervous system, heart, GI and liver.
b. transthyretin amyloidosis
c. Amyloidosis AA- due to chronic inflammatory disorders. Renal, hepatic, GI.
70 yo AAM comes to your office with arthritis that is getting worse and increased fatigue. Examination is normal. You discover on initial lab evaluation that his hematocrit is 32 and his creatinine is 2.2. His skull Xray shows lytic lesions.
.
What diagnostic test should I order to screen for myeloma?
Serum protein electrophoresis
B2 microglobulin, bone marrow exam, bone xrays all for confirmation
Which result would make me want most to treat a paraproteinemia?
.
Which of the following is not a cause of amyloid deposits? Monoclonal serum light chains Transthyretin Chronic osteomyelitis Rheumatoid arthritis Polyneuropathy
polyneuropathy is a complication of amyloidosis, not a cause
Myeloma is
a. monoclonal plasma cell proliferation
b. mature B cell malignancy
What is seen in PBS of myeloma?
rouleaux formation (immunoglobulins cause RBCs to adhere)
What complications of myeloma lead to renal insufficiency?
hypercalcemia
light chain deposition in renal tubules
MGUS (monoclonal gammopathy of unknown significance)
asymptomatic increase in abnormal protein. Can progress to monoclonal B cell malignancy.
Bone marrow clonal plasma cells <10%
Smoldering myeloma
more M-protein
bone marrow clonal plasma cells >10%
asymptomatic
Beta-2 microglobulin
..
Which treatment presently provides best survival in Myeloma?
autologous BMT (although IMID and proteosome inhibitors are new, but will become very important)
Which signs are similar in Waldenstrom’s and Myeloma?
both cause monoclonal gammopathy
Myeloma -lytic bone lesions Waldenstrom's - lymphadenopathy - splenomegaly - cryoglobinemia
Waldenstrom’s Macroglobulinemia
(low grade lymphoma with excess monoclonal IgM)
a. > 40 yo
b. hepatosplenomegaly and lymphadenopathy
c. Abnormal bleeding because high protein level effects platelet function.
d. Hyperviscosity syndrome
What are the clincial features of hyperviscosity syndrome?
headache, blurred vision, altered mental status, ataxia
serum viscosity >4
Treatment for Waldenstrom’s macroglobulinemia?
Bortezomib
Rituximab (CD20, unlike plasma cells)
Autologous BMT
plasmapheresis for hyperviscosity
Amyloid treatment
Light Chain Amyloid- Myeloma like therapy (bortezomib and BMT)
Transthyretin Amyloid- Liver transplant
AA Amyloid- Treat chronic disease
