Paraproteinaemias. Multiple myeloma.
Amyloidosis.
Part 2
Dr. Gábor Mikala
Waldenström Macroglobulinemia
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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
Mayo Clin Proc, Sept 2010
Hyperviscosity syndrome
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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
Macroglobulinemia: Principles of Therapy
• Observation in patients with asymptomatic disease.
• Active drugs for therapy
– Alkylating agents: Chlorambucil, Cytoxan
– MAbs: Rituximab
– Purine analogues: Fludarabine, Cladribine
– BCR inhibitors (ibrutinib)
– Bendamustine
– Steroids
– Bortezomib
– Thalidomide analogues
Plasma Cell Disorders Manifest Due to Clonal Immunoglobulin
AL Amyloid
Light chain deposition dz
Neuropathy
Cryoglobulinemia
Acquired vWD
What is amyloid (amylin : starch-like)?
• Def : Homogeneous, Pink, extracellular ,
pathologic material.
Nature of Amyloid
A. Physical Nature : non branching protein
fibrils 7.5 -10 nm in diameter. Beta pleated
sheet.
B. Chemical nature :
95% Protein Fibril
Primary systemic amyloidosis
Disease name
Multiple
Myeloma
Type of
Precursor
amyloid in the
tissue
AL
Ig lambda
(or kappa
chains)
Secondary systemic amyloidosis
Disease name
Type of amyloid
in the tissue
Chronic inflammatory
disease.
AA
Hemodialysis associated
amyloidosis in chronic
renal failure.
A-beta 2 micro
globulin.
(Aβ2- micro
globulin)
Rheumatoid arthritis
AA
Special stain and amyloid
• Lugol’s iodine : Brown in gross specimen of
heart.
Special stain and amyloid
Congo red ( normal
light)
Congo red ( polarized
light)
Brick red
Apple green
birefringence
Amyloidosis of kidney ; amyloid deposit in the
mesangium of the glomerular tuft
Amyloid in heart : name the stain and
viewing light
Clinical manifestation
Kidney
Nephrotic syndrome,
protenuria, renal failure
Tongue , GIT
Macroglossia,
malabsorpton
Heart
Cardiomegaly, heart
failure
Bone marrow
Fracture/ Multiple
involvement in
myeloma
Multiple Myeloma.
Clinical Settings Where Ig Deposition Diseases (Including AL
Amyloid) Should Be Suspected In Pts With Monoclonal Ig
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Congestive Heart Failure
Neuropathy (including autonomic neuropathy)
Nephrotic syndrome, Renal Failure
Malabsorption
Hepatosplenomegaly
Carpal tunnel syndrome – especiall if bilateral
Macroglossia
Unexplained constitutional symptoms
„Racoon-eye” palpebral suffusions
Diagnostic Approach in Suspected AL Amyloid
Principles 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.
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Melphalan
Steroids
Proteasome Inhibitors (bortezomib)
Thalidomide/lenalidomide
• Experimental therapy directed at the amyloid
Conclusion
• 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.