1. Paraproteinaemias. Multiple myeloma. Amyloidosis. Part 2 Dr
Paraproteinaemias. Multiple myeloma. Amyloidosis. Part 2 Dr. Gábor Mikala

2. Waldenström 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

3. Mayo Clin Proc, Sept 2010

4. Hyperviscosity 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

5. 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

6. Plasma Cell Disorders Manifest Due to Clonal Immunoglobulin
AL Amyloid
Light chain deposition dz
Neuropathy
Cryoglobulinemia
Acquired vWD

7. What is amyloid (amylin : starch-like)?
Def : Homogeneous, Pink, extracellular , pathologic material.

8. Nature of Amyloid
Physical Nature : non branching protein fibrils nm in diameter. Beta pleated sheet.
Chemical nature :
95% Protein Fibril

9. Primary systemic amyloidosis
Disease name
Type of amyloid in the tissue
Precursor
Multiple Myeloma AL
Ig lambda (or kappa chains)

10. 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

11. Special stain and amyloid
Lugol’s iodine : Brown in gross specimen of heart.

12. Special stain and amyloid
Congo red ( normal light)
Brick red
Congo red ( polarized light)
Apple green birefringence

13. Amyloidosis of kidney ; amyloid deposit in the mesangium of the glomerular tuft

14. Amyloid in heart : name the stain and viewing light

15. Clinical manifestation
Kidney
Nephrotic syndrome, protenuria, renal failure
Tongue , GIT
Macroglossia, malabsorpton
Heart
Cardiomegaly, heart failure
Bone marrow involvement in Multiple Myeloma.
Fracture/ Multiple myeloma

16. Clinical Settings Where Ig Deposition Diseases (Including AL Amyloid) Should Be Suspected In Pts With Monoclonal Ig
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

17. Diagnostic Approach in Suspected AL Amyloid

18. 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.
Melphalan
Steroids
Proteasome Inhibitors (bortezomib)
Thalidomide/lenalidomide
Experimental therapy directed at the amyloid

19. 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.