Definition
• Cardiac amyloidosis is caused by the deposition of insoluble extracellular fibrillar material
• Can be restricted to the heart or can be systemic
Clinical features
Epidemiology
• Primary (AL) amyloidosis is the most common form of systemic amyloidosis in the United States and is associated with multiple myeloma in 5% to 15% of cases
• The risk of isolated cardiac amyloidosis is four times greater in African Americans
Presentation
• Can be isolated to the heart or can be part of systemic amyloidosis
• Senile amyloidosis tends to only involve the heart
• Can be seen as a restrictive cardiomyopathy, dilation, or arrhythmias
• Can also be asymptomatic
Prognosis and treatment
• In AL amyloidosis, cardiac involvement leads to rapidly progressive cardiac dysfunction
• Familial and senile forms of amyloidosis lead to mild clinical symptoms and slower progression
• Supportive treatment
• Cardiac transplantation may be considered in hereditary transthyretin-related amyloidosis
Pathology
• The heart grossly has a consistency that varies from normal to firm and rubbery; numerous small translucent nodules can also be apparent
• Microscopically there are varying amounts of eosinophilic amorphous deposits in the interstitium, conduction system, pericardium, endocardium, and arteries
Immunopathology/special stains
• Congo red special stain produces an orangeophilic staining under light microscopy and classic apple-green birefringence under polarized light
• Trichrome stain produces a grayish-blue staining
• Thioflavin stain produces fluorescence
• Electron microscopy shows perimyocytic and intramural vascular deposits; the fibrils measure 7 nm to 10 nm
• Amyloid deposits are laser microdissected and analyzed by mass spectrometry to determine type of amyloid (DNA mutational analysis is done if transthyretin amyloid is present)
Main differential diagnosis
• Fibrosis: a trichrome special stain is positive; however, it has a grayish-blue tinctorial appearance in amyloidosis and is dark blue in fibrosis
Fig 1 Cardiac amyloidosis. There is an eosinophilic amorphous interstitial infiltrate characteristic of amyloid; there is also myocyte hypertrophy, low (A) and high (B) powers.
Fig 2 Cardiac amyloidosis. Incidental finding of small nodules of amyloid deposits are seen in this atrial appendage resected from a 78-year-old during valve replacement.
Fig 3 Cardiac amyloidosis. A, Light microscopic picture shows a positive Congo red special stain for amyloid. B, This light microscopic picture shows both interstitial and vascular amyloid deposits. C,This same slide under polarized light has characteristic apple-green birefringence seen in amyloidosis.
Fig 4 Cardiac amyloidosis. A trichrome stain showing grayish blue staining seen in amyloidosis.
Fig 5 Cardiac amyloidosis. Electron microscopic images showing the typical fibrils of amyloid surrounding cardiac myocytes (A and B).