Amyloidosis

Question 1

describe amyloids and staining of them

Answer 1

• amyloid is a misfolded protein that deposits in the extracellular space, thereby damaging tissues
• multiple proteins can deposit as amyloid
  
  • B-pleated sheet configuration
  • Congo red staining and apple-green birefringence when viewed microscopically under polarized light
    
    • on E/M, non-branching fibrils + non-fibrillary component (P component)

Question 2

describe primary amyloidosis

Answer 2

• systemic deposition of AL amyloid, which is derived from immunoglobulin light chain
  
  • associated with plasma cells dyscrasias (e.g. multiple myeloma)

Question 3

describe secondary amyloidosis

Answer 3

• systemic deposition of AA (amyloid-associated) amyloid derived from SAA (serum amyloid-associated) proteins
  
  • SAA is an acute phase reactant that is increased in chronic inflammatory states, malignancy, and Familial Mediterranean fever
• long-standing inflammation leads to elevated SAA levels, and ultimately the AA form of amyloid deposits

Question 4

describe the pathogenesis of amyloidosis (AL protein vs AA protein)

Answer 4

Question 5

describe senile cardiac amyloidosis vs. familial amyloid cardiomyopathy

Answer 5

• senile cardiac amyloidosis
  
  • non-mutated serum transthyretin deposits in heart
  • usually asymptomatic
• familial amyloid cardiomyopathy
  
  • mutated serum transthyretin deposits in heart
  • leads to restrictive cardiomyopathy

Question 6

describe amyloidosis in Alzheimer disease

Answer 6

• Aβ amyloid deposits in brain, forming amyloid plaques
• derived from β-amyloid precursor protein, APP (on chr. 21)

Question 7

describe dialysis-associated amyloidosis

Answer 7

• β2-microglobulin deposits in joints
  
  • β2-microglobulin found in MHC I

Question 8

describe what is seen in the image

Answer 8

Question 9

describe what is seen in the image

Answer 9

Question 10

describe what is seen in the image

Answer 10

Question 11

describe the image and staining

Answer 11

Question 12

describe the systemic amyloidosis

Answer 12

• immunocyte dyscrasias
  
  • excess of Ig and light chains (Bence Jones) by abnormal B cells (multiple myeloma)
    
    • AL type; most common
• reactive systemic
  
  • AA, found in chronic inflammation
    
    • TB, Hodgkins lymphoma, RA, IBD
• hemodialysis
  
  • B-2 microglobulin
• Familial (hereditary)
  
  • fibrils in these familial polyneuropathies are made up of mutant forms of transthyretin (ATTRs) or AA
  • familial Mediterranean fever

Question 13

describe localized amyloidosis

Answer 13

• single organ/system involvement
• various chemical compositions
• lungs, skin, tongue, joints, bladder, thyroid, pancreas (T2D)
• senile cardiac and cerebral (Alzheimer’s)

Question 14

describe the macroscopic features of amyloidosis

Answer 14

• enlargement by excess extracellular space
  
  • or
• atrophy of organ by amyloid involvement of blood vessels
• firm in consistency
• waxy-pale in color

Question 15

describe microscopic features of amyloidosis

Answer 15

• glassy pink on H&E
• salmon-red on Congo red
• apple green on polarization
• around parenchymal cells
• in blood vessels, nerves

Question 16

amyloidosis of the ___ is the most common and most serious feature of the disease

explain this

Answer 16

amyloidosis of the kidneys is the most common and most serious feature of the disease

• most are markedly enlarged
• most present with proteinuria
  
  • foamy/frothy urine
• affects predominantly the glomeruli
• eventual renal failure = dialysis

Question 17

describe what is seen in the image

Answer 17

Question 18

describe amyloidosis of the spleen

Answer 18

• very commonly involved
• marked enlargement
• the deposits may be virtually limited to the splenic follicles, producing tapioca-like granules on gross examination, aka “sago spleen”

Question 19

describe what is seen in the image

Answer 19

Question 20

describe what is seen in the image

Answer 20

amyloid deposts first appear in the space of Disse, and then progressively enlarge to encroach on the adjacent hepatic parenchyma and sinusoids

the trapped liver cells undergo compression atrophy and are eventually replaced by sheets of amyloid

Question 21

describe amyloidosis of the heart

Answer 21

• can occur either as localized or systemic amyloidosis
  
  • localized = senile amyloidosis
    
    • non-mutated serum transthyretin deposits in heart
    • also seen in young adults
  • systemic = AL type
    
    • mutated serum transthyretin deposits in the heart leading to restrictive cardiomyopathy
• microscopically: deposits are seen in practically all layers of heart in the extracellular space, often suffocating and causing atrophy of the myocardial fibers

Question 22

describe what is seen in the image

Answer 22

amyloidosis of the adrenal gland: patient would present with hypoadrenalism