Localized Amyloidosis of the Larynx: Evidence for Light Chain Composition

Abstract

We report the biochemical characterization of amyloid fibrils from a patient with localized amyloidosis of the epiglottis and larynx. Biopsy specimens showed amorphous material consistent with amyloid deposits with a plasmacytic infiltrate. Both plasma cells and amyloid deposits stained positively by immunohistochemistry for kappa light chains. Amyloid fibrils were isolated. The major constituent resolved as a 13 kd band was sequenced and found to be consistent with a kappa 1 light chain. A tryptic digest was carried out and 3 tryptic peptides were sequenced defining the first 45 residues of the protein and residues 110 through 119. Four amino acid substitutions were found, 3 of which have not been described previously. This study defines the immunoglobulin origin of amyloid deposits in localized amyloidosis. The benign nature of localized amyloidosis suggests that a localized clone of plasma cells producing an amyloidogenic light chain may represent the pathogenetic mechanism of this disease, which appears to be a form of plasma cell dyscrasia.

Primary Localized Amyloidosis of the Intestine: A Pathologist Viewpoint

“…The otherwise benign polyclonal plasma cells produce monoclonal immunoglobulin light chains (L) that are deposited as AL amyloid [ 45 ]. It is still possible that the deposition of amyloid results from the inability of the body to clear light chains produced by plasma cells [ 46 ]. Amyloid deposits in the intestine are usually irreversible but can sometimes be reversible with chemotherapy treatment, especially with melphalan and steroid therapy [ 16 ].…”

One Hundred Cases of Localized Laryngeal Amyloidosis ‐ Evidence for Future Management

“…9 Although there is no proven link to smoking, vocal misuse, or recurrent infections, 1,9 one theory suggests a response of circulating precursor proteins, plasma cells, and/or immunoglobulins, to localized injury and inflammation. Another more likely theory suggests a localized collection of monoclonal plasma cells 10,11 and inability of the body to clear the excessive or misfolded immunoglobulins produced by monoclonal plasma cells found in the mucosa (mucosa-associated lymphoid tissue or MALT). Westermark hypothesizes further that giant cells, prevalent in localized amyloid deposits but not systemic, are important in transforming the immunoglobulin light chain into the misfolded amyloid fibrils.…”

Localized Vocal Cord Amyloidosis

“…Antiserum to K or L light-chain protins may be used but this is not as reliable as anti-AA staining (1). Amino acid sequence studies of laryngeal amyloid have shown that the amyloid fibrils are derived from amyloid immunoglobulin light chain (6,7). In this case report, amyloidosis was confirmed by the Congo red staining of the biopsy specimen.…”