2nd Exam: Plasma Cell Disorders Flashcards
CD 3, 4, 5:
T lymphocytes
CD 13:
most granulocytees
CD15:
granulocyes
List the 5 heavy chains:
GAMED
Common Ig’s?
IgG: most common, A and M: next most common, D and E: fairly uncommon
1 plasma cell, 1:
Ig (one type of each chain)
3 classifications o plasma cell disorders:
MGUS, plasma cell myeloma Plasmsmacytoma
MGUS:
Monoclonal gammopathy of undertermined significance
Solitary lesion of neoplastic monoclonal plasma cells morphologically the same as myeloma, bone or soft tissue:
plasmacytoma
Related Ig producing disorders:
Ig depositiondisease, ie primary amyloidosis, Heavy chain disease, adn lymphoplasmacytoid Lymphoma
progressive, incurable, excess light chains bind, producing amyloidosis: abnormal protein deposition in one or more organs or body systems.
primary amyloidosis
Heavy chains produced in Heavy Chain Disease:
G, A, or M, no light chains
Lymphoplasmacytoid Lymphoma
Subset IgM producing: Waldenstrom’s Macroglobulinemia
Waldenstrom’s Macroglobulinemia is what type of disorder:
Lymphoplasmacytoid lymphoma
Disorder of malig neo of lympholyctes stuck at lympho and plasma cell differentiation border:
Lymphoplasmacytoid Lymphoma
Antigen binding-sites on Ig’s are made of:
amino ends (NH2)
kappa/lambda light chain ration in peripheral blood:
2:1
Digests IgG:
papain
IgG is broken into these via papain:
2 identical FAB, 1 Fc
FAB sf:
Fragment antigen binding
Fc sf:
fragment-crystallizable (constant end of Ig)
Major Ig in serum:
G
Major Ig of external secretions:
A
1st Ig presesnt after primary antigenic stimulus:
M
Ig that crosses placenta and Ig that does not.
G, M
Ig in trace amts in normal serum:
D
define reaginin:
allergic
This has reaginic antibody activity
IgE
IgE is involved in:
immediate hypersensititvity, eosinophilic response
IgG crosses placenta via:
active transport
When is IgG produced:?
response to 2nd exposure to an antigenic stimulus
Major Ig in GI secretions:
A
Ig considered large size “macrolobulin:
M, polymer/ pentamer
1st Ab produced in infectious mononucleosis:
M
infectious mononucleosis develops from:
EBV esp. college age
Test for these Ig’s if you suspect infectious mononucleosis:
M, G, and A
Ig levels that rise in response to EBV virus:
M and A
Ig’s levels increased with recent exposure to EBV, recent mono infection:
lots of M, no G
Test for mono, IgG is high and IgM is not:
had mono in past, not current infection
Order of Ig presentation in mono infection:
M then G, stays high for a while later
If Rafi were tested now for mono, which Ig would be present in higher conc’s?
G
Ig produced to fight issues in GI tract:
A
EBV is aka:
HHV-4
Swollen lymph nodes and suspected mono indicates:
G could be high or not, mono in past
Slide appearance of plasma cells when they are mounting a response:
making lots of Ig, bluish cytoplasm, eccentric nucleus
Polyclonal proliferation of plasma cells that are each different, many types of Ig, some kappa, some lambda:
polyclonal plasma cell proliferation
Plasma cells proliferate in response to:
antigen presentation by B lymphos, many lines searching for best Ig to produce
polyclonal plasma cell proliferation, neoplastic or malignant cell line?
either
neoplastic or malignant cell line, one or many cells of origin?
1, same products, 1 light chain, 1 Ig type, 1 marker
Leads to a monoclonal serum protein or “M” protein:
production of a monoclonal light chain by neoplastic plasma cells or B-lymphos
Stain this for monoclonal plasma cells:
either light chain
SPEP sf:
serum protein electrophoresis, agarose gel electrophoresis to id different proteins in serum via size and electrical charge
Clinical syms pointing toward monoclonal gammopathy:
abnormal SPEP, intermittent, “non-sp” joint pain, no swelling or redness
Test to use when a monoclonal serum protein is suspected:
SPEP
Normal SPEP has, abnormal has:
5 regions, goal post spikes at either end/ gamma region: albumin on L, Gamma globulin on R
List the 5 regions in normal SPEP:
serum albumin, alpha-1, alpha 2, beta, gamma globulins
Spike on normal SPEP with 2 hills:
beta
What spike would be down in SPEP w nutritional problems?
albumin region spike
What does a broad, increased band in gamma region indicate?
fighting infection, probably polyclonal
Test to measure kidney function:
BUN/ Creatinine
Normal % of plasma cells in bone marrow:
less than 5%
What test next with slight increase in monoclonal protein in blood, all else WNL, spike in y-region of SPEP:
IFE: Immunofixation electrophoreses
IFE sf:
Immunofixation electrophoreses
When to do IFE:
to further evaluate SPEP findings, id and characterize monoclonal proteins in serum or urine
In IFE, after proteins from urine or serum are separated they are incubated with:
antisera against Ig of interest, precipitates at sites of Ag-Ab reaction
Band intesity of IFE correlates with:
protein concentration
Tx for MGUS:
none, asymptomatic, simply follow
monoclonal serum protein is aka:
“M” protein
TF? Presence of an expanded clone of Ig-secreting cells is considered neoplastic.
F, does not always progress to overt malignancy
What is present in serum with MGUS?
small amt monoclonal serum protein (“M” protein”, <3gm/dl), bm plasma cells <10%
Most common cause of monoclonal gammopathy:
MGUS
MGUS common in this pop:
elderly: 3% over 50yo, 5% over 70yo
Symptoms of MGUS:
none
MGUS may evolve to become:
well defined palsma cell or lymphoid neolpasm
Risk of MGUS progression per year:
1.6%, increased likelihood of having it every year
Clinical symps of plasmacytoma:
peristant pain in discreet region, osteolytic lesion on x-ray, elevated IgG, IgA and IgM: low normal, low % of plasma cells in bm, sheet of monoclonal plasma cell, high density (1 light chain type) in biopsy
Tx of plasmacytoma:
focal radiation therapy
Plasmacytoma has similar clinical presentation as:
myeloma, but no lytic bone lesions, normal bm biopsy
Name of plasmacytoma found in bone:
“solitary plasmacytoma of bone”
Name of plasmacytoma found in soft tissue:
extra-osseous plasmacytoma
Most common site of solitary plasmacytoma of bone
Spine/vertebra
Fraction of plasmacytomas that progress to myeloma or additional plasmacytomas:
up to 2/3
Initial symptoms of plasmacytoma :
swelling or bone pain, lesion on xr
Clinical sym of plasma cell myeloma:
dizziness, light headed, inc bone pain, IgG increased, decreased IgA and IgM, generalized osteoporosis, lytic lesions/ dec bone mass, impaired renal function (abnormal BUN/creatinine), bm packed with monoclonal plasma cells, many abnormally shaped
TF? There is a finite level to the amt of Ig your body can produce.
T. One level goes up, another goes down
Plasma cell myeloma is aka:
multiple myeloma
Abnormal SPEP is found in:
monoclonal gammopathy and multiple/ plasma cell myeloma
Difference bw SPEP of monoclonal gammopathy and multiple/ plasma cell myeloma:
monoclonal: posts about same height, multiple: y-region taller than albumin region
Clinical dx of symptomatic multiple myeloma:
M-protein in serum or urine, bm clonal plasma cells or plasmacytoma, related organ tissue impairment: CRAB, suppression of normal Ig’s leading to infection, excessive IgG or IgA (kidney damage)
CRAB sf:
Hypercalcemia, renal insufficiency, anemia, bone lesions
Clinical problems pts with multiple myeloma may encounter:
CRAB
Clinical dx of asymptomatic multiple myeloma:
M protein in serum/urine (<3% g/dl) AND/OR 10% or more clonal plasma cells in bm marrow BUT no related organ or tissue impairment (no CRAB) or myeloma related symptoms
asymptomatic multiple myeloma is aka:
smoldering plasma cell myeloma
If a young person got MM (rare) this procedure would probably be done:
bm transplant
Median age for MM onset:
70yo, 1% US cancer deather
Most common plasma cell dyscrasia:
MM
Tx for MM:
chemo, radiation for sp lesions (palliation), bm transplant
define palliate:
make less unpleasant wo removing cause:
Hypercalcemia seen in MM is due to:
bone destruciton
Inceased levels of these Ig’s can lead to kidney damage:
G, A
Suppression of normal Ig’s leads to:
infection
This presents as “punched out” bone:
MM
What to suspect if a pt breaks a bone during normal life activities:
MM, underlying bone destruction
Hypercalcemia leads to:
confusion, weaknesss, lethargy, deposits
Why does anemia present as a symptom of MM?
bm infiltration
Can MM involve organs besides bone and soft tissues?
ys
Most common site of lytic bone lesions in MM:
vertebrae
somnolent:
sleepy, drowsy
Lab results with MM:
inc blood Ca2+ CPR, B2-microglobulin, anemia, monoclonal protein id’ed using SPEP and IFE
B2-microglobulin
component of MHC class I mol’s, on all nucleated cells
Why to take multiple xr’s with MM:
punched out appearance is not present throughout entire body
Lesions of vertebrae with red marrow, juicy, cellular, many abnormal plasma cells, rounded lesions suspect this:
MM
Disorder that can lead to collapsed vertebrae:
MM
Do normal plasma cells have nucleoli?
no
Ig inclusions are called:
Russell bodies
Russel bodies are seen in:
normal plasma cells and myeloma cells, pts with M spike
cells with many Ig inclusions:
Mott cells, pts with m spike
TF? The presence of mott cells indicates malignancy.
F.
Found in the vacuoles of mott cells and russell bodes:
Ig
Tx to reverse spinal cord compression due to MM:
emergency bm biopsy, chemo
BM findings with MM:
increase plasma cells, often abnormal, variable disease distribution in bm
Peripheral blood findings with MM:
anemia w or wo dec wbcs, thrombocytopenia (dec platelets), maybe plasma cells, stacking of rbcs (rouleaux) due to inc serum protein, maybe plasmacytoid lymphos (increased calcium, right? CRAB?)
Cause of roleaux:
inc serum protein
What is roleaux?
rbc stacking due to inc protein in blood
Why is the background bluish when staining of MM peripheral blood:
protein staining
To test for amyloid
Congo red stain
amyloid due to MM can cause
enlarged tongue
leading causes of death with MM:
1: infections, #2: kidney failure
Cause of kidney damage with MM:
monoclonal light chains form tubular casts, toxic to tubular epi cells, plasma infiltration, inc Ca2+ levels due to renal vasoc, leading to intra-tubular Ca+2 deposits, infection, amyloid deposition (how are IgG and A involved?)
monoclonal light chains in urine:
Bence Jones proteins
Kindey can be damaged by hypercalceremia due to:
renal vasoc, leads to intra-tubular calcium deposition
use dipstick urine test to detect:
only albumin, not immunoglobulin
to detect monoclonal light chains in urine:
urine protein electrophoresis
Tests to order of pts with MM and kidney issues:
SPEP and immunohistochemistry
How do light chains damage kidney tubules?
solidify to form light chain casts, cast nephropathy
formation of plugs in renal tubules from free Ig light chains leading to renal failure in context of MM:
cast nephropathy
Where does Ca2+ precipitate in body?
random spots, including kidney
Myeloma staging is based on:
bone lesions, anemia, inc blood Ca2+, creatinine, Ig levels, Bence-Jones proteins in urine
Creatinine measures are related to:
kidney function
Hct sf:
hematocrit
Tx for myeloma:
radiation, chemo, stem cell transplant, velcade, Interferon-y (anti-IL-6 agent), interferon-a, thalidomide, bisphosponates
Velcade is aka:
bortezomib
Anti-IL6-agent:
interferon-y
Function of bisphosphonates:
inhibit bone resorption, reduce osteoclasts
Drugs used for chemo tx of MM:
melphalan, cyclophosphamide, prednisone
Side effect of chem tx for MM:
myelosuppression
Velcade (bortezomib):
proteasome inhibitor, inc myeloma cell response to chemo, induce apoptosis of tumor cells, side effect: neuropathy
Drugs used to tx MM besides chemo:
velcade (bortezomib), anti-Il-6 agents (iterferon-y), interferon-a,m thalidomide, bisphosphonates
We want to decrease IL-6 in MM tx because:
IL-6 promotes myeloma cell proliferation
Function of interferon-a:
turns off osteoclasts, aimed at bone lesions (how do we ensure only the lesion osteoclasts are turned off?)
Functions of thalidomide:
anti-TNFa-immunomodulating, inhibits angiogensis
Pink stained kidney indicates:
amyloid in kidney, light chain deposition, deproteinaseous material
Test to detect amyloid in kidney:
Congo red staining, polarized light, apple green
Plasma cell disorder with increased amyloid levels (amyloidosis):
any
Fibrillary protein deposited in various tissues, may damage organs:
amyloid
plasma cell neoplasm, amyloid derived from all or part of monoclonal Ig light chain secreted by plasma cells:
primary amyloidosis
TF? Amyloidosis is always related to plasma cell disorders.
F, can be seen by itself
These combine to form amyloid fibrils:
protofilaments
Test to id amyloid fibers:
congo red, apple green birefringence under polarized light or EM
Risk factors for primary amyloidosis:
60-70yo, male (2/3)
How to dx primary amyloidosis:
demonstration of amyloid in biopsy specimen (Congo red stain)
Test to id the type of amyloid in 1’ amyloidosis:
mass spec
Oral manifestations of amyloidosis:
enlarged tongue, periorbital bleeding, should biopsy
Waldenstrom’s macroglobulinemia:
IgM secretions, monoclonal protein (macroglobulin), diffuse infiltrate of neoplastic B-cells (small lymphos with plasmacytoid features) in bm, lymph nodes, liver and spleen
Median survival of Waldenstrom’s macroglobulinemia:
4y
Clinical presentation of Waldenstrom’s macroglobulinemia:
weaknes, fatigue, w8 loss, lymphadenopathy, large liver or spleen, hyperviscocity syndrome, typically 50-60yo
hyperviscocity syndrome:
visual and nerve problems, bleeding (acquired factor deficiencies, cryoglobulinemia, proteins insoluble at temps below body)
macroglobulin Ig:
IgM
Ig precipitation at cold temperatures, in fingers is indicative of:
Waldenstrom’s macroglobulinemia
Hyperviscocity in Waldenstrom’s macroglobulinemia is due to:
Inc IgM production, neoplastic production, can’t get through caps, think of eyes, bleeding, absorb clotting factors
Tx for blood build up in eyes due to Waldenstrom’s macroglobulinemia:
plasmaphoresis to remove protein: blood run through machine, prevent retina destruction
Gelling or precipitation of a monoclonal protein at low temp:
cryoglobulin
Ig most often to become a cryglobulin:
IgM
Clinical presentation of cryoglobulinemia:
sluggish blood flow, purpura, Reynaud’s phenomenon, gangrene
artery spasm, dec blood, typically fingers, sometimes toes, rarely nose, ears, lips, turns white, then blue, numb, painful, red and burning when blood flow returns, Recurrent attacks - brittle nails w longitudinal ridges:
Reynaud’s phenom
