Diagnosing and typing amyloidosis. (A) A Congo red stained renal biopsy (left) shows the apple-green birefringence in polarized light (right) indicative of amyloidosis, 200× (images were acquired using an Olympus BX51 microscope equipped with a 20×/0.5 NA objective and mounted DP12 digital camera, and were further processed [cut out and white balanced] with Adobe Photoshop CS2). (B) Characteristic amyloid fibrils extracted from the postmortem spleen of a patient with rapidly progressive κ AL are shown in a transmission electron micrograph, 100 000× (image was obtained at the Sloan-Kettering Institute Core Electron Microscopy Facility). Fibrils are 7 to 10 nM in diameter and variable in length. (C) Exon 4 of TTR shows heterozygosity (left, arrow) in an African American man with amyloidosis due to the Val122Ile variant (codons for aa 121, 122, and 123 are shown). Homozygotes (right, arrow) are rare but can present with severely symptomatic disease in their early 50s. (D) An example of immunogold electron microscopy (IEM) is shown, 50 000× (courtesy of Dr Carl O'Hara, July 2008; the image was obtained at the Boston University School of Medicine Experimental Pathology Laboratory Service Core). Tissue sections on grids were treated overnight with primary polyclonal rabbit anti–human antibodies (for κ and λ light chains and for TTR) and then with goat anti–rabbit gold secondary antibody conjugates. In this instance the patient had a κ light chain paraprotein and mutant TTR. IEM demonstrated ATTR. Note how the gold beads sit along the fibrils. (E) The peptides of the FR1 portion of the κ light chain from panel B are identified by liquid chromatography and mass spectrometry of the extracted amyloid protein (liquid chromatography/tandem mass spectrometry were performed at the Proteomics Resource Center at Rockefeller University).