Plasma cell neoplasms Flashcards
What are some of the key epidemiological
things about Plasma cell myeloma?
- older adults with a median onset of 70 years
- significantly more common in blacks
- familial clustering
- 3-4x more common in first degree relatives
What are the diagnostic criteria
for symptomatic Multiple Myeloma?
- clonal bone marrow plasma cells >10%
- or biopsy proven plasmacytoma
- plus greater than or equal to 1 of the following:
- organ impairment with CRAB
- high calcium, renal insufficiency, anemia and bone lesions
- > = 1 of malignant bone markers
- 60% bone marrow plasma cells
- serum free light chain ratio >100
- > 1 focal lesion on MRI
- organ impairment with CRAB
What are the diagnostic criteria
for Asymptomatic (smoldering)
Multiple Myeloma?
IMP: both criteria must be met for this diagnosis
- Serum M protein > 3 g/dL (30 g/L)
- or urinary M protein of > 500 mg/day and/or clonal bone marrow plasma cells 10-60%
- or clonal plasma cells 10%
- absence of myeloma defining evens or amyloidosis
What are the renal manifestations of
Multiple Myeloma?
- Acquired renal Fanconi Syndrome
- hypercalcemia and hyperuricemia
- damage the proximal tubules
- hypercalcemia and hyperuricemia
- AL amyloidosis
- often associated with Lambda L.C.
- deposits in vessels of the glomeruli
- Myeloma cast nephropathy
- intratubular crystallization of M protein
- deposits look angulated and cracked
What are the clinical manifestations of
Fanconi renal syndrome?
- inadequate reabsorption in proximal renal tubules
- acidosis
- hypokalemia
- hyperchloremia
What is the cause of a bleeding diathesis
and the hyperviscosity syndrome in
Multiple Myeloma ?
- M protein interferes with coagulation factors
- thrombocytopenia can occur due to marrow involvement
- amyloidosis can lower factor X
Hyperviscosity Syndrome:
- often with IgM, IgA and IgG3 protein
Why are patients with
Multiple Myeloma prone to infections?
- they have hypogammaglobulinemia
- this predisposes them to infection with encapsulated organisms
- Streptococcus pneumoniae
What is the M protein often
encountered in Multiple Myeloma?
- usually heavy chain
- often IgG (55%)
- then IgA (22%)
- IgE is the least common type
- if it is light chain
- Kappa is most common
- BUT IgD myeloma, associated with lambda
What are some of the cytoplasmic
changes seen in Multiple Myeloma?
- Mott cells
- Flame cells
- usually with IgA
- Morula
- Russell bodies
- Gaucher-like
Note: none of these are diagnostic for myeloma
What is the immunophenotype of
Multiple Myeloma?
- Plasma cells (+)
- CD38, CD138, CD56
- Kappa or Lambda
- DO not express:
- CD45 or B cell antigens
- CD19, CD20, CD21, or CD22 or SIg
- CD45 or B cell antigens
What are some unique immunophenotypic markers
that can be expressed by Multiple Myeloma ?
- CD56:
- suggestive of aggressive behavior
- absent in plasmablastic lymphoma and plasma cell leukemia
- BCL-1/Cyclin D1
- seen in some cases and correlates with t(11;14)
- Myelomonocytic markers
- CD117, CD13, CD33, CD11b and CD15
- seen in 10-30%
What is the prognosis for Multiple Myeloma?
- mean survival is 3-5 years
- Adverse Factors:
- High B2 microglobulin
- High plasma labeling index
- High stage
- specific cytogenetics
What is the most common abnormal locus
genetically in Multiple Myeloma?
- 14q32
- IgH gene
What is the most common structural abnormality
seen in Multiple Myeloma?
- t(11;14)(q13;q32)
- CCND1/IgH
What FISH findings are high risk,
associated with OS of 3 years?
- del 17p
- t(14;16)
- t(14;20)
What are FISH findings associated with
intermediate risk MM, OS 4-5 years?
- del 13
- t(4;14)
- hypodiploid
What are FISH associated findings for
standard risk MM, OS 8-10 years?
- t(11;14)
- t(6;14)
- hyperdiploid
What are key findings of Multiple Myeloma
on flow cytometry?
- dim to absent CD45 with bright CD38
- CD56 v CD19
- neoplastic cells have dim CD19 (or absent)
- express CD56
- cytoplasmic lambda light chain restriction
What is the definition of
plasma cell leukemia?
- absolute plasma cell count >2 x 10^9/ L or 20% plasma cells in the blood
- High incidence of IgE, IgD or light chain myeloma
- CD20 +
- CD56 (-)
- aggressive disease with poor treatment response and survival
What is the definition of Solitary Plasmacytoma?
- often seen in the vertebrae, ribs and pelvis
- two variants are seen
- SP with no bone marrow plasmacytosis or end organ damage
- 10% progress to MM
- SP with minimal marrow plasmacytosis (clonal plasma cells <10%)
- 60% progress to MM
- SP with no bone marrow plasmacytosis or end organ damage
What is the definition of Extraosseous Plasmacytoma?
- commonly arises in the nasal cavity, oropharynx and larynx
- progression to myeloma less frequent
- higher rate of minimal marrow involvement
What is the general definition of an MGUS?
- monoclonal gammopathy without criteria for a plasma cell neoplasm or presence of a B cell neoplasm capable of producing an M protein
- seen in 3% of adults over the age of 50 and 5% of adults older than 70
What are the diagnostic criteria for
Monoclonal gammopathy of unknown significance?
- Monoclonal gammopathy
- < 3 g/dL (30 g/L)
- < 10% of plasma cells in the bone marrow
- no CRAB
- no B cell neoplasm
What is POEMS syndrome and what is
it associated with?
POEMS
- polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes
- caused by Osteosclerotic myeloma
- individuals usually have solitary intraosseous plasmacytomas with thickening of the bony trabeculae
What other clinical situations can
POEMS syndrome be seen in ?
- Plasma cell variant Castlemann’s disaease
- HHV8
