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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 D. McPhail
  • Paul J. Kurtin
  • Surendra Dasari
  • Malinda Butz
  • Cynthia C. Morton
  • W. Edward Highsmith
  • Fang ZhouEmail author
Case Report
  • 51 Downloads

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.

Keywords

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

Notes

Acknowledgements

We acknowledge Mayo Clinic Clinical Tissue Proteomics Laboratory for performing mass spectrometry experiments.

Funding

C. C. Morton is supported by NIDCD R01DC015052 and the University of Manchester NIHR Biomedical Research Centre.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Atreyee Basu
    • 1
  • Nicole J. Boczek
    • 2
  • Nahid G. Robertson
    • 3
  • Samih H. Nasr
    • 2
  • Daniel Jethanamest
    • 4
  • Ellen D. McPhail
    • 2
  • Paul J. Kurtin
    • 2
  • Surendra Dasari
    • 5
  • Malinda Butz
    • 2
  • Cynthia C. Morton
    • 6
    • 7
    • 8
  • W. Edward Highsmith
    • 2
  • Fang Zhou
    • 1
    • 9
    Email author
  1. 1.Department of PathologyNew York University School of MedicineNew YorkUSA
  2. 2.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  3. 3.Department of Obstetrics and GynecologyBrigham and Women’s HospitalBostonUSA
  4. 4.Department of Otolaryngology-Head and Neck SurgeryNew York University School of MedicineNew YorkUSA
  5. 5.Department of Health Sciences ResearchMayo ClinicRochesterUSA
  6. 6.Departments of Obstetrics and Gynecology and of Pathology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  7. 7.Broad Institute of MIT and HarvardCambridgeUSA
  8. 8.University of Manchester, Manchester Academic Health Science CentreManchesterUK
  9. 9.Department of PathologyNew York University Langone Health, Tisch HospitalNew YorkUSA

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