myeloma Amyloidosis Part 2 Dr Gábor Mikala Waldenström Macroglobulinemia Uncontrolled proliferation of lymphoplasmacytes producing IgM Median age 63 years Presents with weakness fatigue ID: 914312
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Slide1
Paraproteinaemias
.
Multiple
myeloma
.
Amyloidosis
.
Part 2
Dr. Gábor
Mikala
Slide2Waldenström
Macroglobulinemia
Uncontrolled proliferation of
lymphoplasmacytes
producing
IgM
Median age
63 years
Presents with weakness, fatigue,
epistaxis
, blurred vision
Bone pain and
lytic
bone lesions are uncommon (<5%)
25% have
hepatomegaly
,
splenomegaly
and
lymphadenopathy
Hyperviscosity
is common
Slide3Mayo
Clin
Proc, Sept 2010
Slide4Hyperviscosity syndrome
bleeding (nasal and gums)
blurred vision
dizziness, headaches, ataxia
congestive heart failure
retinal vein engorgement, and papilledema
rarely occurs with serum viscosity <4 centipoises (cp) (normal 1.8 cp)
IgM pentamer
Slide5Macroglobulinemia: Principles of Therapy
Observation in patients with asymptomatic disease.
Active drugs for therapy
Alkylating
agents:
Chlorambucil
,
Cytoxan
MAbs
:
Ritux
imab
Purine analogues:
Fludarabine, Cladribine
BCR inhibitors
(ibrutinib)
BendamustineSteroids
Bortezomib
Thalidomide analogues
Slide6Plasma Cell Disorders Manifest Due to
Clonal
Immunoglobulin
AL
Amyloid
Light chain deposition
dz
Neuropathy
Cryoglobulinemia
Acquired
vWD
Slide7What is amyloid (amylin : starch-like)?
Def : Homogeneous, Pink, extracellular , pathologic material.
Slide8Nature of Amyloid
Physical Nature
: non branching protein fibrils 7.5 -10 nm in diameter. Beta pleated sheet.
Chemical nature
:
95% Protein Fibril
Slide9Primary systemic amyloidosis
Disease name
Type of amyloid in the tissue
Precursor
Multiple Myeloma
AL
Ig lambda
(or kappa chains)
Slide10Secondary systemic amyloidosis
Disease name
Type of amyloid in the tissue
Chronic inflammatory disease.
AA
Hemodialysis associate
d
amyloidosis in chronic renal failure.
A-beta 2 micro globulin.
(A
β
2-
micro globulin
)
Rheumatoid arthritis
AA
Slide11Special stain and amyloid
Lug
o
l’s iodine : Brown in gross specimen of heart.
Slide12Special stain and amyloid
Congo red ( normal light)
Brick red
Congo red ( polarized light)
Apple green birefringence
Slide13Amyloidosis of kidney ; amyloid deposit in the mesa
ng
i
um of the glomerular tuft
Slide14Amyloid in heart : name the stain and viewing light
Slide15Clinical manifestation
Kidney
Nephrotic syndrome, protenuria, renal failure
Tongue , GIT
Macroglossia, malabsorpton
Heart
Cardiomegaly, heart failure
Bone marrow involvement in Multiple Myeloma.
Fracture/ Multiple myeloma
Slide16Clinical Settings Where
Ig
Deposition Diseases (Including AL Amyloid) Should Be
Suspected
I
n
P
ts
With Monoclonal
Ig
Congestive Heart Failure
Neuropathy (including autonomic neuropathy)
Nephrotic syndrome, Renal FailureMalabsorption
Hepatosplenomegaly
Carpal tunnel syndrome –
especiall if
bilateral
Macroglossia
Unexplained constitutional symptoms
„Racoon-eye” palpebral
suffusions
Slide17Diagnostic Approach in Suspected AL Amyloid
Slide18Principles of Management in AL Amyloid
Therapeutic approach guided by age, organ involvement.
Cardiac involvement and dysfunction as a major predictor.
Therapy directed at the underlying clonal plasma cells.
Melphalan
Steroids
Proteasome
Inhibitors (
bortezomib
)
Thalidomide/
lenalidomide
Experimental
therapy
directed at
the amyloid
Slide19Conclusion
Plasma cell dyscrasias are a heterogeneous group of disorders.
Clinical presentation may be due to the clone itself or the properties of the secreted Ig.
Therapy largely directed (if indicated) at reducing the underlying clone.