Amyloidosis Pathology

Amyloidosis Definition

• Extracellular deposition of amyloid substance, mainly in walls of blood vessels, basement membranes, and along reticulin fibers.
• Amyloid is a protein substance, but named "amyloid" due to its starch-like reaction with iodine and sulfuric acid, giving a blue color.

Staining of Amyloid

• Gross Staining:
  • Lugol's iodine stains amyloid dark brown and the rest of tissue pale yellow.
  • Iodine and 1% sulfuric acid stain the amyloid blue.
• Microscopic Staining:
  • Hematoxylin and eosin stain: Amyloid appears homogenous and eosinophilic.
  • Congo red stain: Amyloid is stained orange red, with apple-green bipolar refringence under polarizing light.
  • Metachromatic stains (e.g. crystal violet or methyl violet): Amyloid deposits are stained rose red, while the rest of tissues are stained violet.

Nature of Amyloid

• 90% of amyloid is a fibril protein, and the remaining 10% is a glycoprotein called P component.
• Amyloid fibril proteins may be:
  • AL (amyloid light chain protein of immunoglobulins), secreted by plasma cells in plasma cell neoplasms (e.g. myeloma).
  • AA (amyloid-associated protein), a non-immunoglobulin protein present in serum as SAA, increased in chronic destructive diseases (e.g. tuberculosis).
  • Less common proteins, such as B2 microglobulin and transthyretin (pre-albumin).

Types of Amyloidosis

Systemic (Generalized) Amyloidosis

• Many organs are affected.
• Causes of death: renal failure, heart failure, malabsorption, and Addison's disease.
• Types:
  • B Cell Dyscrasias (Primary Amyloidosis):
    • AL is secreted due to B lymphocyte and plasma cell abnormalities.
    • Affects heart, tongue, GIT, skeletal muscles, and other organs.
  • Reactive Systemic Amyloidosis (Secondary Amyloidosis):
    • AA is increased in chronic severe destructive conditions.
    • Affects kidneys, liver, spleen, and adrenal glands.
  • Hereditary Amyloidosis:
    • Several types, with AA or transthyretin as the amyloid protein.
    • May be generalized or localized.

Hemodialysis-associated Amyloidosis

• Affects up to 70% of patients with chronic renal failure subjected to chronic hemodialysis.
• Due to deposition of B2 microglobulin, which is not filtered by normal dialysis membranes.
• Deposits seen in joints, synovium, and tendon sheaths.

Localized Amyloidosis

• Senile Amyloidosis:
  • Affects vessels of the brain (gray matter) in Alzheimer's disease.
  • B2 amyloid protein (AB2 protein).
• Amyloid deposits within endocrine tumors:
  • e.g. amyloid deposits within medullary carcinoma of thyroid.
  • The amyloid protein is procalcitonin produced by the tumor cells.
• Idiopathic localized amyloid deposits:
  • May occur in various sites, such as larynx, tongue, urinary bladder, muscles, heart, etc.
  • The amyloid protein is unknown.