AMYLOIDOSIS

Dr. Ung
Pathology
Year 2
 Amyloidosis

• Amyloidosis is a condition associated with a

number of inherited and inflammatory disorders
in which extracellular deposits of fibrillar proteins
are responsible for tissue damage and functional
compromise.

Pathogenesis of Amyloid Deposition

• Amyloidosis is fundamentally a disorder of

protein misfolding.
• More than 20 different proteins can aggregate
and form fibrils with the appearance of amyloid.
 Most common forms
1. The AL ( amyloid light chain ) protein
2. The AA ( amyloid-associated ) fibril
3. A-beta amyloid

Classification
1. Immunocyte Dyscrasias with Amyloidosis(primary
amyloidosis)
2. Reactive Systemic Amyloidosis
3. Familial ( Hereditary ) Amyloidosis
4. Localized Amyloidosis
5. Endocrine Amyloidosis
6. Amyloid of aging
 Immunocyte Dyscrasias with Amyloidosis
• Most common form
• Systemic in distribution
• The AL type
• E.g. amyloidosis associated with multiple
myeloma
Reactive Systemic Amyloidosis
• Systemic in distribution
• AA protein
• Most common causes- tuberculosis,
bronchiectasis, chronic osteomyelitis,
autoimmune states
 Familial ( Hereditary ) Amyloidosis
• Most are rare
• E.g. familial Mediterranean fever
• Fever accompanied by inflammation of serosal
surfaces

Localized Amyloidosis

• Limited to single organ or tissue

• Most often encountered in the lung, larynx, skin,
urinary bladder, tongue, and region of the eye
• AL protein
 Endocrine Amyloid

• Certain endocrine tumours

• E.g. medullary carcinoma of thyroid, islet
tumours of pancreas, pheochromocytoma, and
undiffentiated carcinomas of the stomach

Amyloid of aging

• Elderly patients
• 70s and 80s
• Senile cardiac amyloidosis
 Morphology

• In amyloidosis secondary to chronic

inflammatory disorders, kidneys, liver, spleen,
lymph nodes, adrenals, and thyroid are typically
affected.
• Immunocyte-associated amyloidosis more often
involves the heart, gastrointestinal tract,
respiratory tract, peripheral nerves, skin, and
tongue.
Gross
• The organ is enlarged when amyloid accumulates
in larger amount. The tissue appears gray with
waxy , firm consistency.
Histology
• The amyloid deposition is always extracellular
and begins between cells.
Staining characteristics
• Congo red
• Pink or red colour
• Under polarized light, apple-green birefringence
 Kidney

• The most common and most serious

involvement
• May be abnormally large, pale, gray, and firm
• The amyloid deposits are found principally in the
glomeruli
• total obliteration of the vascular tuft
 Spleen
• Moderate or marked enlargement
( 1 ) Sago spleen- topioca-like granules on gross
examination
• Deposits limited to to the splenic follicles
( 2 ) Lardaceous spleen – large , sheetlike deposits
• Affect splenic sinuses and splenic pulp

Liver

• Massive enlargement
• Extremely pale, grayish , and waxy
• Involve adjacent hepatic parenchyma and
sinusoids
 Heart

• Isolated organ involvement or part of a systemic

distribution
• Minimal to moderate cardiac enlargement
• Gray-pink, dewdrop-like subendocardial
elevations
• Seen in atrial chambers
 Clinical Correlation

• Unsuspected finding at autopsy

• Serious clinical dysfunction
• Nonspecific complaints
• Renal disease
• Hepatomegaly
• Splenomegaly
• Cardiac abnormalities
• Kidney -nephrotic syndrome
• Heart - conduction disturbances or restrictive
cardiomyopathy
• Biopsy and subsequent Congo red staining is the
most important tool in diagnosis
• Prognosis for generalized amyloidosis- poor