Plasma Cell disorders Flashcards
What is the originating cell line that all cells are derived from?
What are the two lineages that deviate from this? –and what cells come from those?
pluripotent stem cells
Myelod: RBC, platelets, monocyte, neutrophils, eosinophils, basophils
Lymphoid: T cell, B cell, Plasma cell
Where do plasma cells develop?
in bone marrow and lymph nodes
What is multiple myeloma? (living room language)
What is it characterized by? (medical language)
bone marrow makes cancerous blood cells.
-neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin (M protein)
Who gets Multiple Myeloma?
- typically a disease of older adults, median age of dx 66
- only 10% of pts are younger than 50yeras
- occurs in all races
Multiple Myeloma Presentation (signs/symptoms)
-signs and symptoms related to infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains.
- lytic bone lesions
- infection
- fractures
- renal failure
- proteinuria
- purpura
- raynauds
- anemia
- Bence Jone protein
- bone pain
- elevated creatinine (byproduct of muscle metab, indicator of kidney function)
- fatigue/general weakness
- hypercalcemia
- weight loss
- anemia (normocytic normochromic) ** related to:
- -bone marrow replacement
- -kidney damage
- -dilution in case of a large M-protein (aby)
- -B12 deficiency
80% of MM patients have abnormal x-rays d/t?
osteopenia (reduced bone mass
osteoporosis (brittle/fragile)
focal lytic bone
pathologic fx
vertebral body compression fx
Why might MM pts have renal failure?
d/t:
- light chain cast nephropathy (called myeloma kidney)
- hypercalcemia
- concurrent light chain amyloidosis
- drug induced renal damage
Amyloidosis= disorder marked by deposition of amyloid (abnormal protein in the bone marrow that gets deposited in an organ or soft tissue)
What are some rare signs and symptoms of MM?
- parasthesias/neurologic disease
- hepatomegaly
- splenomegaly
- lymphadenopathy
- infections
- CNS involvement
- pleural effusion and pulmonary involvement
- extramedullary plasmacytomas (build up of monoclonal plasma cells outside of the bone marrow)
Complete hx and physical exam, what are some specific complaints to pay attention to?
- bone pain
- constitutional sx (I dont feel good)
- neurological sx
- recurrent nagging infections
MM labs?
- CBC w/ diff, peripheral blood smear (wil lsee rouleaux, thrombocytopenia, leukopenia)
- CMP (kidney function and Ca)
- LDH (released during tissue damage)
- beta-2 microglobulin
- c-reactive protein
- serum protein electrophoresis + IF (immuno fixation)
- Urinalysis and 24hr urine collection for electrophoresis + IF
- serum free monoclonal light chain
WHat would you expect to see in SPEP in an MM pt?
Two spikes, one at albumin and another at gamma (Y)
What tests would be ordered if suspected MM?
- serum viscosity if M protein conc is High
- bone marrow aspiration/biopsy w/ immunophenotyping
- conventional cytogenetics
- fluorescence in situ hybridization (FISH)
- Metastatic bone survey–plain radiographs of humeri and femoral bones
- MRI, CT, or PET/CT
What percentage of Bone marrow biopsy would contain clonal plasma cells?
10%
When would you order a pet scan?
- bone pain w/o abnormality along with a normal looking radiograph
- sudden onset of neurologic sx (this is an emergency, compression fx may be pushin on spinal cord in the instance of sudden numb leg)
What three criteria must be met to dx MM?
- presence of serum or urinary monoclonal protein
- presence of clonal plasma cells in bone marrow or a plasmacytoma
- presence of end organ damage felt related to plasma dyscrasia (malfunction, abnormal) Such as:
- increased Ca conc.
- lytic bone lesions
- anemia
- renal failure
What does M-CRAB stand for?
Monoclonal protein
Calcium
Renal failure
Anemia
Bone marrow + bone pain lytic lesions
Monoclonal Gammopathy of Undetermined Significance (MGUS), what three criteria must be met for this dx?
-serum monoclonal protein
MGUS sx and tx
asymptomatic, dont require tx.
“sit on your hands”
Smoldering Multiple Myeloma (SMM), what criteria must be met for dx?
- serum monoclonal protein are >/= 3g/dL and/or bone marrow plasma cells >/= 10%
- no end organ damage related to plasma cell dyscrasia
- this is one step further thant MGUS in the progression to MM.
Indications for tx in MM
- anemia
- hypercalcemia
- renal insuficiency
- lytic bone lesions/severe osteopenia
- extramedullary plasmacytoma
MM Tx:
chemotherapy: survival =3yrs
transplantation: survival 4-5years
Novel agents targeting stromal interactions and associated signaling pathways: survival beyond 5 years
Novel agents: immunomodulating drugs and proteasome inhibitors
What is Waldenstrom macroglobulinemia?
-lymphoplasmacytic lymphoma in the bone marrow with an IgM monoclonal gammopathy in the blood.
cancer affecting B cells, aby IgM, indolent, uncontrolled increase in B cells prolif of B ell interfere with RBC production resulting in anemia.
unique characteristic: B cells produce excess amounts of IgM thickening the blood
Presentation of WM?
most common: weakness, fatigue, weight loss, chronic oozing of blood from nose or gums.
- asymptomatic 25%
- consititutional sx
- bleeding
- neurologic sx
- hyperviscosity (HA, vertigo, diplopia)
- lymphadenopathy
- hepatomegaly
- splenomegaly
- fundoscopic abnormalities
Symptoms of WM?
Cause: tumor infiltration
Sx: anemia, fever, night sweats, weight loss, lymphadenopathy, organomegaly
Causee: Monoclonal IgM
Sx: hyperviscosity, cryoglobulinemia, cold agglutinin, neuropathy, amyloidosis
WM evaluation, what tests will you order?
- CBC
- Platelet function and blood coag.
- Bone marrow examination
- serum protein electrophoresis
- serum viscosity
- serum free light chain
- assay
-CT of abd and pelvis to detect organomegaly
WM Diagnostic Criteria
- IgM monoclonal gammopathy in serum
- 10% or > of bone marrow biopsy demonstrates infiltration by small lymphocytes that exhibit plasma cell differentiation
Tx of WM
- asymptomatic: observe, no Tx
- Symptomatic: rituximab
- High tumor burden (must also be a candidate): hematopoietic cell transplantation
- Hyperviscosity: therapeutic plasmapheresis
