Chapter 8: Amyloidosis Pathology

The text details the fundamental histological characteristics of amyloid, specifically its amorphous eosinophilic appearance on H and E stain and its unique apple-green birefringence when viewed under polarized light after Congo red staining. The summary distinguishes between systemic and localized disease forms, beginning with Primary Amyloidosis (AL type), which is associated with plasma cell disorders like multiple myeloma and involves immunoglobulin light chains. It contrasts this with Reactive Systemic Amyloidosis (AA type), a secondary condition driven by chronic inflammation—such as rheumatoid arthritis, tuberculosis, or osteomyelitis—where the liver produces the acute phase reactant Serum Amyloid A (SAA). Further genetic and iatrogenic causes are explored, including Familial Mediterranean Fever, an autosomal recessive disorder caused by pyrin mutations, and Hemodialysis-associated amyloidosis, where beta2-microglobulin accumulation often leads to carpal tunnel syndrome and joint disease. The discussion extends to localized variants, such as Senile Cerebral Amyloidosis (Alzheimer disease) involving beta-amyloid precursor protein linked to chromosome 21, and Senile Cardiac Amyloidosis, which involves transthyretin (ATTR) deposition and poses a specific risk for heart failure in elderly populations and African Americans carrying the V1221 mutation. Endocrine-specific depositions in conditions like medullary thyroid carcinoma and type 2 diabetes are also covered. Finally, the chapter outlines the clinical consequences of these deposits, including nephrotic syndrome, restrictive cardiomyopathy, macroglossia, and malabsorption, while noting that definitive diagnosis relies on tissue biopsy of sites like the abdominal fat pad or rectal mucosa.