Amyloidosis Pathology

Study Notes

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.

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.

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).

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.

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.

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.

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