First Report of Bilateral External Auditory Canal Cochlin Aggregates (“Cochlinomas”) with Multifocal Amyloid-Like Deposits, Associated with Sensorineural Hearing Loss and a Novel Genetic Variant in COCH Encoding Cochlin

Atreyee Basu, Nicole J. Boczek, Nahid G. Robertson, Samih H. Nasr, Daniel Jethanamest, Ellen McPhail, Paul J. Kurtin, Surendra Dasari, Malinda Butz, Cynthia C. Morton, W. Edward Highsmith, Fang Zhou

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalHead and Neck Pathology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Ear Canal
Sensorineural Hearing Loss
Amyloid Plaques
Congo Red
Amyloid
Deafness
Polarization Microscopy
Microfibrils
Birefringence
Peptides
Isoleucine
Middle Ear
Inner Ear
Amino Acid Substitution
Protein C
Phenylalanine
Mass Spectrometry
Electron Microscopy
Pathology
Staining and Labeling

Keywords

  • Amyloid
  • Cochlin
  • Congo red
  • Deafness
  • External ear canal stenosis
  • Liquid chromatography tandem mass spectrometry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oncology

Cite this

First Report of Bilateral External Auditory Canal Cochlin Aggregates (“Cochlinomas”) with Multifocal Amyloid-Like Deposits, Associated with Sensorineural Hearing Loss and a Novel Genetic Variant in COCH Encoding Cochlin. / Basu, Atreyee; Boczek, Nicole J.; Robertson, Nahid G.; Nasr, Samih H.; Jethanamest, Daniel; McPhail, Ellen; Kurtin, Paul J.; Dasari, Surendra; Butz, Malinda; Morton, Cynthia C.; Highsmith, W. Edward; Zhou, Fang.

In: Head and Neck Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Basu, Atreyee ; Boczek, Nicole J. ; Robertson, Nahid G. ; Nasr, Samih H. ; Jethanamest, Daniel ; McPhail, Ellen ; Kurtin, Paul J. ; Dasari, Surendra ; Butz, Malinda ; Morton, Cynthia C. ; Highsmith, W. Edward ; Zhou, Fang. / First Report of Bilateral External Auditory Canal Cochlin Aggregates (“Cochlinomas”) with Multifocal Amyloid-Like Deposits, Associated with Sensorineural Hearing Loss and a Novel Genetic Variant in COCH Encoding Cochlin. In: Head and Neck Pathology. 2019.
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abstract = "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.",
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AU - Basu, Atreyee

AU - Boczek, Nicole J.

AU - Robertson, Nahid G.

AU - Nasr, Samih H.

AU - Jethanamest, Daniel

AU - McPhail, Ellen

AU - Kurtin, Paul J.

AU - Dasari, Surendra

AU - Butz, Malinda

AU - Morton, Cynthia C.

AU - Highsmith, W. Edward

AU - Zhou, Fang

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