REVIEWAmyloidosis

Clerk: 吳昱甫

Introduction• Amyloidosis definition: Extracellular deposits of fibrillary proteins• Binds wide variety of proteoglycans (蛋白聚糖 ) and glycosaminoglycans (葡萄胺聚糖 )• E.G. heparin sulfate, dermatan sulfate,

plasma proteins, serum amyloid P component

Amylose• Proteoglycans &

glycosaminoglycans• Resembled starch• Unstable and self-

associated• Full of β-sheet polypeptide chains• They are called Fibrils

doi: 10.1073/pnas.1202071109

Fibrils Formation

http://www.chem.umass.edu/~vachet/Research.html

Amyloid• Consisted by

fibrils• Congo-red• Apple-green

birefringence

Robbins Pathology, 9/e

Pathogenesis• Normally, misfolded proteins are

degraded intracellularly in proteasomes, or extracellularly by macrophages.• It appears that in amyloidosis, these

quality control mechanisms fail, allowing the misfolding protein to accumulate outside cells.• Disease depends on where it deposits

Pathogenesis

Robbins Pathology, 9/e

Classification• Primary amyloidosis

• AL form• Most common form of amyloidosis• 5% to 15% of patients have multiple myeloma

• Reactive systemic amyloidosis• AA form• Chronic infection (TB, osteomyelitis,

skin-infection)• Chronic inflammation (autoimmune related:

IBD, RA)• Tumors (RCC, Hodgkin lymphoma)

Classification• Familial (hereditary) amyloidosis• Familial Mediterranean fever (pyrin and

inflammasome)• Localized amyloidosis• Nodular deposits• Infiltration of plasma cells and lymphocytes

• Amyloidosis of Aging• TTR type• Senile cardiac amyloidosis

Morphology – Kidney• Most common in organs (and most

serious)• Deposited principally in glomeruli• Within mesangial matrix

• Clinical course• Nephrotic syndrome• With severe proteinuria

http://www.pathologyatlas.ro/amyloidosis-kidney-pathology.php

Morphology - Heart• Usually the AL form• Senile amyloidosis, TTR form• Deposited principally between myocardial fibers• Clinical course• Conduction

disturbance• Arrhythmias• Cardiomyopathy

http://www.e-heart.org/Pages/03_Cardiomyopathy/03_Cardiomyopathy_Amyloidosis_006.htm

Back to The Case

Back to The Case• Laryngeal amyloidosis is rare, accounting

for 0.5-1% of benign laryngeal tumors. • However, the larynx is one of the more common sites in the head and neck for amyloid deposition. • In contrast with tongue amyloidosis,

laryngeal involvement is usually due to a localized deposition of AL amyloid, and is only rarely a manifestation of systemic amyloidosis.

Back to The Case• The most common presenting symptom is slowly progressive dysphonia; acute airway compromise is rare. • Amyloid deposition may cause diffuse

thickening of the true or false cords. • Discrete lesions take the form of smooth,

non-ulcerative swellings around 1.5 cm across, and may occur anywhere in the supraglottis, glottis or subglottis. • Amyloid deposition in the hypopharynx is

very rare.

Reference1. Robbins Pathology, 9/e2. The Systemic Amyloidoses, Rodney H. Falk,

M.D., Raymond L. Comenzo, M.D., and Martha Skinner, M.D.; N Engl J Med 1997; 337:898-909

3. Molecular Mechanisms of Amyloidosis, Giampaolo Merlini, M.D., and Vittorio Bellotti, M.D., Ph.D.; N Engl J Med 2003; 349:583-596

4. Head and neck manifestations of amyloidosis; The Otorhinolaryngologist 2013; 6(1): 35–40