Morphologic findings in the common fibrinogen A α-chain amyloidosis E526 variant. (A) Congo red stain in renal biopsy (×100 magnification) in fibrinogen A α-chain amyloidosis. Extensive amyloid infiltrate with glomerular enlargement and replacement of the normal glomerular architecture by amyloid deposition, with almost no amyloid in the interstitium. (B) Same section as panel A viewed between crossed polars shows apple green birefringence typical of amyloid deposits. (C) Congo red stain in histologic sample from a ruptured spleen (×100 magnification) in AFib E526V exhibits extensive splenic amyloid deposits with predominantly trabecular and subcapsular distribution. (D) Endomyocardial biopsy specimen (×100 magnification) in a patient with AFib E526V and renal failure, with abnormal echocardiography (patient 19, Tables 1 and 2). Cardiac histology stained with Congo red demonstrates extensive, diffuse amyloid deposition in the myocardium. An endomyocardial vessel is demonstrated at the center of the section, showing complete replacement of its entire wall thickness by amyloid deposition. (E) Bright apple green birefringence of the amyloid deposits in myocardium and endocardial vessels of section in panel D under cross-polarized light. (F) Endomyocardial biopsy (×40 magnification) hematoxylin and eosin stain, in a patient with AFib E526V variant (patient 16, tables), on hemodialysis for 18 months, who had severe carotid atherosclerosis, and whose echocardiography showed normal wall thickness with impaired left ventricular relaxation. (G) Congo red stain demonstrates amyloid deposition at the periphery of an atrophic muscle fiber from the same sample (×100 magnification). (H) Apple green birefringence under polarized light in previous section. (I) Arterial intima atheroma (×100 magnification) excised during endarterectomy for the indication of 80% carotid stenosis in the same patient as in panels D and E. Congo red stain demonstrates extensive amyloid deposition within the intima and atheromatous plaque (arrows). The Congo red material exhibited strong apple green birefringence. Immunostaining with antifibrinogen antibodies was not performed because normal (wild-type) fibrinogen is expected to be part of the thrombus, and therefore a positive immunohistochemistry could not be reliably positive for a diagnosis of variant fibrinogen amyloidosis. (J) Transmission electron microscopy (×150 000 magnification) images of the atheroma in panel F demonstrates fibrillar material with fibril diameter of approximately 10 nm, compatible with amyloid. Fibril extraction and characterization revealed the amyloid atheromatous plaque to consist wholly of variant E526V fibrinogen. (K) Images from subsequent coronary angiography in the same patient, carried out to exclude significant asymptomatic coronary atherosclerosis as part of generalized amyloid angiopathy, in context of findings in panels F through I. Left anterior oblique cranial angiogram of left coronary artery shows diffuse atheroma in the left anterior descending coronary artery (LAD) with heavy calcification (arrows). (L) Left anterior oblique angiographic projection of the right coronary artery (same patient as in panel K) shows diffuse atheroma throughout its course. Leads from dual chamber pacemaker inserted for the indication of bradyarrhythmias are also shown (arrow).