Amyloidosis

 

In MM the amyloid is comprised of light chains, most often lambda, arranged in a B-pleated sheet.
Most likely to occur in patients with Bence Jones proteinuria.
Findings that suggest the presence of amyloidosis are:
 - Macroglossia
 - Bilateral swelling of the shoulder joints
 - Skin nodules (on the face, lips, ears, and trunk)
 - Peripalpebral purpura ("raccoon eyes")
 - Significant proteinuria on common urine dip sticks

Amyloidosis is a disease characterized by deposition of amyloid fibrils in the tissues. These fibrils have a twisted beta-pleated sheet structure and are birefringent when viewed under polarized light after staining with Congo red.
Several unrelated proteins may give rise to amyloid fibrils.

 

 

Asymptomatic immunoglobulin light chain amyloidosis (AL) at the time of diagnostic bone marrow biopsy in newly diagnosed patients with multiple myeloma and smoldering myeloma. A series of 144 cases and a review of the literature.
Ann Hematol. 2011 Jan;90(1):101-6.
Siragusa S, Morice W, Gertz MA, Kyle RA, Greipp PR, Lust JA, Witzig TE, Lacy MQ, Zeldenrust SR, Rajkumar SV, Russell SJ, Hayman SR, Buadi F, Kumar SK, Dingli D, Dispenzieri A.
Among 144 bone marrow biopsies of patients with multiple myeloma (67 with smoldering myeloma), amyloid was detected in only 2 cases (1%), and none had clinical manifestations suggestive of amyloidosis. Only 1 of 142 patients without amyloid deposition in the bone marrow developed symptomatic amyloidosis during the course of his disease (after 119 months).

 

 

Amyloid seen in a bone marrow biopsy. Eosinophilic appearance when stained with H&E and viewed by light microscopy (courtesy of Dr. Michael G. Bayerl - Hemopathology, Penn State Hershey Cancer Institute):

 

 

 

Amyloid deposits are birefringent when stained with Congo red and viewed under polarized light (courtesy of Dr. Michael G. Bayerl - Hemopathology, Penn State Hershey Cancer Institute):

 

 

 

Amyloid deposits in a marrow biopsy, viewed by light microscopy (left), and under polarized light microscopy (right) (courtesy of Dr. Michael G. Bayerl - Hemopathology, Penn State Hershey Cancer Institute):

 

 

 

Amyloid deposits seen with light microscopy in the endomyocardial biopsy of a patient with cardiac amyloidosis (left). Normal myocardium is shown on the right side (courtesy of Dr. Michael G. Bayerl - Hemopathology, Penn State Hershey Cancer Institute):

 

 

 

 

Primary (AL Amyloidosis) is the most common form (85%) of systemic amyloidosis.
Usually associated with the plasma cell disorders MM and MGUS. If a patient with amyloidosis has >10% plasma cells in the bone marrow biopsy, patient can be considered to have amyloidosis associated with multiple myeloma.
The deposited fibrils are composed of the variable region of monoclonal immunoglobulin light chains (lambda or kappa) in a beta-pleated configuration. These fibrils are produced by a low-grade intramedullary clonal plasma cell dyscrasia. A fine line distinguishes AL amyloidosis from MM. There are fewer plasma cells in the BM and the lambda light chains are more common than kappa light chains in amyloidosis, whereas the reverse is true in MM.

 

 


Other forms of amyloidosis, not related to multiple myeloma

 

Secondary (AA Amyloidosis)
Associated with several chronic inflammatory diseases:
 - Chronic infections:
      malaria
      TB
      leprosy
      syphilis
      osteomyelitis
      bronchiectasis
 - Autoimmune diseases
      RA
Fibril precursor protein: serum amyloid A protein, an acute-phase reactant protein.

Familial Amyloidosis
Autosomal dominant.
Caused by mutations in the genes encoding:
 1. Fibrinogen A alpha-chain
 2. Transthyretin
 3. Apolipoprotein A-I
 4. Lysozyme
In familial transthyretin amyloidosis (ATTR amyloidosis), the deposited fibrillar proteins are composed of mutant transthyretin protein, a plasma protein that transports retinol-binding protein and 25% of thyroxine in the blood.

Hemodialysis Amyloidosis
Associated with renal hemodialysis.
Fibril precursor protein: beta2-microglobulin.

 

 


Giampaolo Talamo, M.D.