AMYLOIDOSIS
Amyloid
Conditions associated
with deposition amyloid,
are called Amyloidosis
Morphology
• The affected organ is
enlarged and appears
gray with a waxy and
firm consistency
• With progressive
accumulation of
amyloid, it produces
pressure atrophy of
adjacent cells.
• Histologically, the amyloid deposition is always
extracellular.
• With the light microscope and H&E stain,
amyloid appears as an amorphous, eosinophilic,
hyaline, extracellular substance.
• The most commonly used staining technique
for detection of amyloid is Congo red dye.
• Congo red dye under light microscope imparts
a pink-red color to amyloid deposits.
• Under polarized light the Congo red-stained
amyloid shows apple-green birefringence
Pathogenesis and Classification
of Amyloidosis
More than 20 distinct forms of amyloid proteins
have been identified
AL
It is produced by plasma cells and made up
(amyloid light
chain) of Ig light chains.
AA
It is synthesized in the liver. Involved in
(amyloid-
associated) chronic inflammatory disorders.
Aβ2m (β2-
microglobulin) A component of the MHC class I molecules.
TTR
A normal serum protein that binds and
(Transthyretin)
transports thyroxine and retinol.
Conditions Associated With AA
Chronic Inflammatory
Diseases Neoplasia
Rheumatoid arthritis Renal carcinoma
Tuberculosis Hodgkin lymphoma
Bronchiectasis
Chronic osteomyelitis
Ankylosing spondylitis
Crohn disease
Ulcerative colitis
Classification of Amyloidosis
Major
Clinicopathologic
Associated Diseases Fibril Precursor Protein
Category
Protein
Systemic (Generalized)
Amyloidosis
Immunocyte dyscrasias with Multiple myeloma AL Immunoglobulin
amyloidosis light chains, chiefly
(Primary Amyloidosis) λ type
Reactive systemic amyloidosis Chronic AA SAA
(Secondary Amyloidosis) inflammatory
conditions
Hemodialysis-associated Chronic renal failure Aβ2m β2 microglobulin
amyloidosis
Major Chemically
Clinicopathologic Associated
Fibril Related Precursor
Category Diseases
Protein Protein
Hereditary Amyloidosis
Familial Mediterranean AA SAA
fever
Familial amyloidotic ATTR Transthyretin
neuropathies
Systemic Senile Amyloidosis ATTR Transthyretin
Chemically
Major
Clinicopathologic Related
Associated Diseases Fibril
Category Precursor
Protein
Protein
Localized Amyloidosis
Senile cerebral Alzheimer Aβ APP
disease
Medullary carcinoma of A Cal Calcitonin
thyroid
Islets of Langerhans Type 2 diabetes AIAPP Islet amyloid
peptide
Isolated atrial amyloidosis AANF Atrial
natriuretic
factor
Laboratory Diagnosis
1. Biopsy
• E.g Kidney, rectal or gingival tissues
H&E staining
Congo red staining
Electron microscopy
2. Serum and urine protein electrophoresis
3. Abdominal fat and Bone marrow aspirates
