A Mysterious Trigger for Serum Amyloid A (SAA)-Associated Amyloidosis: Insights From an Autopsy Study

Abstract

Amyloidosis refers to a heterogeneous group of disorders characterized by the extracellular deposition of insoluble fibrillar proteins, leading to tissue damage and functional impairment. Among these, serum amyloid A (SAA) amyloidosis, previously termed secondary amyloidosis, arises in the context of chronic inflammatory conditions. While common causes include autoimmune diseases and chronic infections, the underlying etiology remains unidentified in a subset of cases. We report a rare case of SAA-associated amyloidosis in a 29-year-old male with a history of childhood-onset cystic bronchiectasis. The patient presented with progressive renal dysfunction and was diagnosed with systemic amyloidosis based on histopathological evaluation. Common autoimmune and infectious etiologies were excluded during life. An autopsy revealed alpha-1 antitrypsin deficiency as the underlying cause of chronic pulmonary inflammation, manifesting as cystic bronchiectasis, which likely triggered sustained elevation of serum amyloid A and subsequent amyloid deposition.

Keywords: alpha-1 antitrypsin deficiency; autopsy findings; cystic bronchiectasis; hyaline globules; saa-associated amyloidosis.

Figure 1. Gross and microscopic findings of kidneys.

(A) Gross photograph of the kidneys showing enlargement with nodular capsular surface. (B) Microscopy reveals amorphous, acellular deposits in the mesangium (H&E, 400x). (C) These deposits are congophilic (Congo red, 400x) and show apple-green birefringence under polarized light (D, 100x). (E) Immunohistochemistry reveals strong positivity for serum amyloid A (SAA) protein (400x). (F) Ultrathin electron microscopy shows randomly arranged fibrils measuring 8-12 nm in diameter.

Figure 2. Demonstration of amyloidosis involving different organs.

(A) Microscopy of spleen showing amyloid deposition within the sinusoids, sparing the periarteriolar lymphoid sheath, producing a lardaceous appearance (H&E, 100x). (B) Congo red stain demonstrates apple-green birefringence under polarized light (100x). (C)-(F) Similar congophilic amyloid deposits are observed in the hepatic artery, portal vein, small intestine, pituitary, and bone marrow (Congo red, 100x).

Figure 3. Gross and microphotographs of lung and liver.

(A) Gross photograph of both lungs showing bronchiectasis. (B) Spongy emphysematous changes involving the lower lobes. (C) Microscopy reveals panacinar emphysema (H&E, 100x). (D) Higher magnification shows ruptured and floating interalveolar septa (H&E, 400x). (E) Microscopy of the liver showing ground-glass-like globules in periportal hepatocytes (H&E, 400x). (F) PAS stain highlights hyaline globules in periportal hepatocytes (PAS, 400x). (G) These globules are resistant to diastase digestion (PAS-D, 400x). (H) Immunostaining for alpha-1 antitrypsin shows strong positivity in the hyaline globules (DAB chromogen, 400x). PAS-D: periodic acid-Schiff with diastase, DAB: 3,3'-Diaminobenzidine.