What is seen in Waldenstrom Macroglobulinemia?
- High levels of IgM lead to sx's of hyper-viscosity
- Older adults, commonly in assoc. w/ lymphoplasmacytic lymphoma
Findings of multiple myeloma can be remembered with the mnemonic CRAB.
- Renal abnormalities
- Bone lytic lesions / Back pain
Multiple myeloma is more common in which sex, ethnicity, and what is peak age of incidence?
- More common in men
- African descent
- Peak age = 60-70 y/o
Multiple myeloma is associated with diverse rearrangements of which gene and deletions of?
Rearrangements involving IgH; deletions of 13q and overexpression of D cyclins
High serum levels of what cytokine are seen in pt's with active Multiple Myeloma and is associated with what?
IL-6 = important plasma cell GF; associted with poor prognosis
What finding in the peripheral blood of multiple myeloma is due to the high levels of M proteins; is it specific to MM?
- Rouleaux formation = red cells sticking together in linear arrays
- Characteristic finding, but NOT specific
Which cytologic variant seen in multiple myeloma is due to dysregulated synthesis and secretion of Ig leading to multiple grapelike cytoplasmic droplets within plasma cells of bone marrow?
Plasma cell tumors, like MM, are positive for what markers?
CD138 (aka syndecan-1) and often express CD56
What are the most significant complications associated with Multiple Myeloma?
- Recurrent bacterial infections due to ↓ production of normal Igs = most common cause of death
- Renal insufficiency from Bence-Jones proteinuria (light chains toxic to tubular epithelial cells)
What are the diagnostic lab findings for multiple myeloma; how is definitive diagnosis made?
- Definitive dx requires BM exam; usually contains >30% plasma cells w/ considerable atypia
- Typically >3 gm/dL of Ig (M protein) and/or >6 mg/dL of urinary Bence-Jones proteins
What is the most common monoclonal Ig ("M protein") seen with Multiple Myeloma?
How are translocations involving cyclin D1, deletions of 13q or 17p, and the t(4;14) associated with prognosis in Multiple Myeloma?
- Involvement of cyclin D1 = assoc. w/ good outcome
- Deletions of 13q or 17p and the t(4;14) = more aggressive
What are sx's of smoldering myeloma; findings in BM and serum?
- Patients are asymptomatic; about 75% progress to MM over 15-year period
- Plasma cells make up 10-30% of cells in marrow
- Serum M protein is >3 gm/dL
What is the most common plasma cell dyscrasia?
Monoclonal Gammopathy of Uncertain Significance (MGUS)
How does solitary osseous plasmacytoma differ from extraosseous plasmacytomas in terms of progression?
- Solitary osseous plasmacytoma almost invariably progresses to MM, over 10-20 years
- Extraosseous plasmacytomas, particularly of upper respiratory tract can be cured by local resection
Characteristic sx's and serum findings in Monoclonal Gammopathy of Uncertain Significance (MGUS)?
- By definition, patients are asymptomatic!
- Serum M protein levels is <3 gm/dL
Lymphoplasmacytic lymphoma is a neoplasm of which cells and most often arises in which age group?
- B-cell neoplasm of older adults; usually 6th-7th decade
- Superficial resemblence to CLL/SLL; but differs in that majority of tumor cells undergo terminal differentiation to plasma cells
In lymphoplasmacytic lymphoma, the plasma cell component most commonly secretes what and this leads to?
Secretes monoclonal IgM, often sufficient enough to cause hyperviscosity syndrome (aka Waldenstrom Macroglobulinemia)
How are the pathologic features of lymphoplasmacytic lymphoma different from MM?
- Complications from secretion of free light chains (i.e., renal failure and amyloidosis) = rare
- Bone destruction does NOT occur
Virtually all cases of lymphoplasmacytic lymphoma are associated with acquired mutations in what gene?
What are dominant presenting complaints and common features seen in pt with lymphoplasmacytic lymphoma?
- Usually non-specific and include weakness, fatigue, and weight loss
- LAD, hepatomegaly, and splenomegaly in 50% pt's
- Anemia due to marrow infiltration is common
- 10% pt's have autoimmune hemolysis due to cold agglutinins
Lymphoplasmacytic lymphoma pt's with higher levels of IgM (Waldenstorm Macroglobulinemia) are more likely to have what signs/sx's?
- Visual impairment
- Neurologic problems; such as HA, dizziness, deafness, and stupor
- Cryoglobulinemia; producing sx's such as Raynaud's and cold urticaria
Lymphoplasmacytic lymphoma is uncurable, but what can be done to alleviate the sx's of a high IgM load?
Which disorder associated with monoclonal gammopathy is characterized by a demyelinating peripheral neuropathy?
POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes)
Virtually all mantle cell lymphomas have what translocation; which genes invovled?
t(11;14) creating cyclin D1-IgH fusion gene
The t(11;14) cyclin D1-IgH fusion gene in mantle cell lymphoma contributes to the pathogenesis how?
Up-regulation of cyclin D1 promotes G1---> S-phase progression
Mantle cell lymphoma most often presents when and in what sex?
5th-6th decased w/ male predominance
Mucosal involvement of the small bowel or colon producing polyp-like lesions (lymphomatoid polyposis) is most often seen with what form of NHL?
Mantle Cell Lymphoma
What is the most common presentation of Mantle Cell Lymphoma; which sites commonly involved?
- Most common is painless LAD
- Sx's related to involvement of gut, spleen, liver, and BM are common
Which makers expressed by Mantle Cell Lymphoma help to distinguish it from CLL/SLL?
- CD5 (+) and CD23 (-)
- Also express high levels of cyclin D1; most (+) for CD19 and CD20