Plasma cell disorders Flashcards
_______ % MM patients have no identifiable M component
1
Light chain myeloma pts in whom light chains are catabolised by kidney
Bone pain in MM
Back and ribs
precipitated by movement
Light chain subtype and survival
lambda secretors have shorter survival
fundus in WM
Vascular segmentation
dilatation of retinal veins
Gamma heavy chain disease
franklin
Blood picture in gamma heavy chain disease
thrombocytopenia
eosinophilia
Factors associated with poor prognosis in MM
Histologic atypia
elevated LDH levels
High labeling index
Treatment of hypercalcemia in MM
Hydration
Natriuresis
Glucocorticoids
bisphosphonates
Calcitonin
Only light chains are produced in _______ % of myelomas
20%
Staging system for MM
Rx of hyperviscosity symptoms
plasmapheresis
Difference between Myeloma and waldenstrom macroglobulinemia
Hepatosplenomegaly and lymphadenopathy in WM
Na+ levels in MM
Pseudohyponatremia
Anion gap in MM
low
ROTI
Serum calcium: Increase of more than 1mg/dl above ULN or >11mg/dl
Serum creatinine > 1.95 mg/dl
anemia: Hb less than 2g/dl below LLN or
Bone lesions: Lytic,osteoporosis
Others: Hyperviscosity,amyloidosis,recurrent bacterial infections(>2 episodes/year)
Serum markers playing a role in MM prognosis
IL-6 receptor
HGF
CRP
C-terminal cross-linked telopeptide of collagen I
TGF beta
syndecan 1
Complication of cryoglobulin formation in MM
Raynaud phenomenon
Median age at onset of MM
70 years
qualitative assessment of M component is made by
immunoelectrophoresis
Factors associated with higher incidence of progression of MGUS to myeloma
Non IgG subtype
abnormal Kappa/lambda free light chain ratio
serum M protein > 1.5 g/dl
Splenomegaly and lymphadenopathy in MM
Unusual
__________ % of MM pts will have only light chains in serum and urine
20%
POEMS syndrome
polyneuropathy
organomegaly
endocrinopathy
Multiple myeloma
skin changes
Diagnostic criteria for MGUS
M protein in serum
Bone marrow clonal plasma cells
No evidence of other B cell proliferative disorders
No myeloma-related organ or tissue impairment (no end organ damage, including bone lesions)
Time relation between fall in M component and symptomatic improvement in MM after therapy
Fall in M component lags behind symptomatic improvement
__________ % of pts present with biclonal or triclonal gammopathy
1
Bone pain due to METs differs from that due to MM by
nocturnal pain
MM is uncommon under the age of
40 years
Plasma cell leukemia
Plasma cells > 2000/µL
presentation of gamma heavy chain disease
fever
lymphadenopathy
hepatosplenomegaly
anemia
Difference btw IgM myeloma and WM
IgM myeloma:
Lytic bone lesions
CD138 positive cells in bone marrow
Autoimmune conditions associated with M component
RA
MG
Cold agglutinin disease
Skin changes in POEMS syndrome
hyperpigmentation
hypertrichosis
skin thickening
digital clubbing
Cd of plasma cells
CD138
Alpha heavy chain disease
seligman
Most common infections in MM
pneumonia
pyelonephritis
Neuropathy in MM
More often sensory
associated with IgM
Important feature of level of M protein after therapy
Rate of its increase after therapy
Symptoms of Hyperviscosity occur at ______ centipoise
4
Difference btw MM and MGUS
Labeling index >1% in Myeloma
Treatment of MM variants
Highly responsive to local radiation
40Gy
Type of anemia in multiple myeloma
Normocytic normochromic
Lymphadenopathy in poems syndrome resembles
castleman disease
Causes of recurrent infections in MM
Hypogammaglobulinemia
low CD4 count
defective neutrophil migration
therapy related(dexamethasone)
alpha heavy chain disease is characterised by
infiltration of the lamina propria of the small intestine with lymphoplasmacytoid cells that secrete truncated alpha chains
Heavy chain diseases
Gamma
alpha
Mu
Amount of light chains normally excreted per day
<10mg
common pathogens causing infections in MM
Lungs: s.pneumoniae,s.aureus,klebsiella pneumoniae
Urinary tract: E.coli and other gram negative pathogens
Antigenic determinants
Isotype
Allotype
idiotype
Characteristics of MM variants
younger age at onset
survival > 10 yrs
M component in
Neoplastic diseases associated with M component
CLL
Lymphomas of B or T cell origin
CML
Breast,colon Ca
Diagnostic criteria for asymptomatic Myeloma (Smoldering Myeloma)
M protein in serum 30 g/L and/or
Bone marrow clonal plasma cells 10%
No myeloma-related organ or tissue impairment (no end organ damage, including bone lesions)a or symptoms
Reliable marker of tumor burden in
M component
Course of MM variants
Solitary bone plasmacytomas may recur in other bony sites or evolve into myeloma
Extramedullary plasmacytomas rarely recur or progress
Causes for DVT in MM
Thalidomide or lenalidomide
mu heavy chain disease is associated with
CLL
Major clinical manifestation of WM
hyperviscosity syndrome
Bone marrow in WM
>10% lymphoplasmacytic infiltrate(surface IgM+,CD19+,CD20+,CD22+,Cd10-,CD23-)
Mast cells
Response to therapy in MM is assessed by
Reduction in bone pain,hypercalcemia,anemia,infections
Which is effective in AKI in MM?
Plasmapheresis to remove light chains
causes of bone changes in MM
Activation of osteoclasts
inhibition of osteoblasts
tumor expansion
Cytogenetic alterations in MM
13q,17p deletions
t(11;14)
t(4;14)
t(14;16)
hypodiploidy
Most common cause of renal failure in MM
hypercalcemia
Earliest manifestation of tubular damage in MM
Type 2 RTA
Most common heavy chain disease
alpha heavy chain disease
Skin diseases associated with M component
Lichen myxedematosus(papular mucinosis)
Necrobiotic xanthogranuloma
presentation of alpha heavy chain disease
chronic diarrhoea
weight loss
malabsorption
extensive mesenteric and paraaortic adenopathy
% of myeloma preceded by MGUS
100%
Diagnostic criteria for Nonsecretory Myeloma
No M protein in serum and/or urine with immunofixation
Bone marrow clonal plasmacytosis 10% or plasmacytoma
Myeloma-related organ or tissue impairment (end organ damage, including bone lesions)
most distinctive symptom of gamma heavy chain disease
palatal edema due to involvement of waldeyer ring
rule of 10 in MM
>10% plasma cells in BM
10% of hematologic neoplasms
10% have smoldering myeloma
endocrine manifestations of POEMS syndrome
amenorrhea
Impotence
gynacomastia
Hyperprolactinemia
hypothyroidism
DM
adrenal insufficieny
protenuria in multiple myeloma
nearly all light chains
no albumin as glomerulus is intact
Light chain excretion falls within _______(time) of treatment
first week
renal disease in WM
Uncommon(as only 20% excrete light chains and there are no bone lesions and hypercalcemia)
Causes of anemia in MM
Marrow infiltration by plasma cells
Decreased erythropoietin secretion by kidney
hemolysis
Hematopoiesis inhibitory factors
Megaloblastic anemia due to B12 or folate
_________ % of MGUS develop Myeloma
1% per year
Malignancy associated with alpha heavy chain disease
mediterranean lymphoma
M component in gamma heavy chain disease
Usually IgG1
found in both serum and urine
doesnot react with light chain antibody
Normal relative serum viscosity
1.8
Plasma Cell disorders
MM
WM
Primary amyloidosis
heavy chain diseases
Plasma cell leukemia is common in
IgD(12%) and IgE(25%) myelomas
Rx of heavy chain diseases
combination chemotherapy used to treat low-grade lymphoma
osteoclast activating factors in MM
IL-6
TNF
VEGF
RANK
Lymphotoxin
MIP 1 alpha(macrophage inhibitory factor)
Macroglobulin in WM has specificity for
Myelin associated Glycoprotein
Untreated IPSID pts progress to
lymphoplasmacytic and immunoblastic lymphoma
Serum alkaline phosphatase in MM
Normal
Rx of infections in MM
IV gamma globulins
No role for vaccines or prophylactic antibiotic admn
Sensory neuropathy in MM
IgM
Thalidomide
Bortezomib
Other manifestations of POEMS syndrome
Peripheral edema
ascites
pleural effusion
fever
thrombocytosis
Diagnostic criteria for Symptomatic Multiple Myeloma
M protein in serum and/or urine
Bone marrow (clonal) plasma cells or plasmacytoma
Myeloma-related organ or tissue impairment (end organ damage, including bone lesions)
Ig subtypes in MM associated with hyperviscosity syndromes
IgM
IgG3
IgA
Classic triad of Myeloma
Marrow plasmacytosis>10%
lytic bone lesions
serum and/or urine M component
Neurological disease associated with Monoclonal component
5% of sensorimotor neuropathy
Most common symptom in myeloma
Bone pain (70%)
Diagnostic criteria of Solitary Plasmacytoma of Bone
No M protein in serum and/or urine
Single area of bone destruction due to clonal plasma cells
Bone marrow not consistent with multiple myeloma
Normal skeletal survey (and MRI of spine and pelvis if done)
No related organ or tissue impairment (no end organ damage other than solitary bone lesion)
Non neoplastic conditions associated with M component
sarcoidosis
parasitic diseases
cirrhosis
gaucher
pyoderma gangrenosum
gamma heavy chain disease is frequently associated with
RA
alpha heavy chain disease
seligman disease
Usual sites of extramedullary plasmacytosis
nasopharynx and nasal sinuses
Minimum concentration of monoclonal antibody to be detected by electrophoresis
0.5 g/dl
Partially reversible renal diseases in MM
Light chain deposition disease
light chain cast nephropathy
amyloidosis
Causes of Renal failure in MM
Hypercalcemia
urate nephropathy
light chain deposition disease
amyloidosis
drug induced(NSAID,Bisphosphonates)
contrast dye
role of radioisotope bone scanning in MM
No role as there is no osteoblastic activity
cord compression in MM
Radiation therapy
Causes of neurologic symptoms in MM
Hyperviscosity
cryoglobulinemia
amyloid deposits
hypercalcemia
antineuronal antibodies
POEMS
therapy related
nerve compression
Features responsible for higher risk of progression from smoldering myeloma to MM
bone marrow plasmacytosis >30%
abnormal kappa/lambda free light chain ratio
serum M protein >30 g/L (3 g/dL)
light chain isotype in WM
Kappa(80%)
Suppression of osteoblatic activity in MM is due to
dickhoff(DKK-1)
Rx of relapsed myeloma
Lenalidomide
bortezomib
bortezomib and liposomal doxorubicin
Side effects of bisphosphonate Rx
osteonecrosis of jaw
renal dysfunction(rare)
persistent localised pain in MM
pathological #
Rx of WM
Fludaribine
Cladribine
rituximab
Cell of origin of WM
Post germinal center B cell
concentrations of different Ig at which hyperviscosity symptoms appear
IgM: 4g/dl
IgG3: 5g/dl
IgA: 7g/dl
% of serum M components
IgG 53%
IgA 25%
IgD 1%
Most common primary bone neoplasm of adults
Multiple myeloma
