Pathogenic variants in COCH, encoding cochlin, cause DFNA9
deafness disorder with characteristic histopathologic findings of cochlin deposits in the inner and middle ears. Here, we present the first case of
deafness associated with bilateral external auditory canal (EAC) cochlin deposits, previously unreported evidence suggestive of cochlin-derived
amyloid formation, and a novel COCH variant. A 54-year-old woman presented with progressive
sensorineural hearing loss and bilateral EAC narrowing by subcutaneous thickening. Excision and histologic evaluation of tissue from both EACs showed paucicellular eosinophilic aggregates containing multiple
Congo red-positive foci with yellow and green birefringence under crossed polarization light microscopy. Mass spectrometry performed on both the
Congo red-positive and
Congo red-negative areas identified cochlin as the most abundant
protein, as well as a low abundance of universal
amyloid signature
peptides only in the
Congo red-positive areas.
Peptides indicative of a canonical
amyloid type were not detected. Electron microscopy showed haphazard, branched microfibrils (3-7 nm in diameter) consistent with cochlin, as well as swirling fibrils (10-24 nm in diameter) reminiscent of
amyloid fibrils. Cochlin immunohistochemical staining showed positivity throughout the aggregates. Sequencing of the entire COCH gene coding region from the patient's blood revealed a novel variant resulting in a non-conservative amino acid substitution of
isoleucine to
phenylalanine (c.1621A>T, p.I541F) in the vWFA2 domain at the
protein's C-terminus. Our findings reveal a new pathologic manifestation of cochlin, raise the possibility of previously undescribed cochlin-derived
amyloid formation, and highlight the importance of thoroughly investigating all aggregative tissue findings in the practice of diagnostic pathology.