Safety and efficacy of superior turbinate biopsies as a source of olfactory epithelium appropriate for morphological analysis

  • Ellen Cristine Duarte Garcia
  • Ana Carolina Rossaneis
  • Alexandre Salvatore Pipino
  • Gustavo Vasconcelos Gomes
  • Fábio de Rezende Pinna
  • Richard Louis Voegels
  • Richard L. Doty
  • Waldiceu Aparecido VerriJr.
  • Marco Aurélio FornazieriEmail author



There is no standardized approach for preserving olfactory function in the side of the nose where biopsy of the olfactory epithelium (OE) is performed. Moreover, a gold standard technique for obtaining human OE in vivo is still lacking. We determined the efficacy of obtaining good-quality OE specimens suitable for pathological analysis from the lower half of the superior turbinate and verified the safety of this procedure in maintaining bilateral and unilateral olfactory function.


In 21 individuals without olfactory complaints and who had undergone septoplasty and inferior turbinectomy OE biopsy was made during septoplasty. Olfactory function, both unilateral and bilateral, was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) before and 1 month after the procedure. Specimens were marked with the olfactory marker protein for confirmation of OE presence.


Ninety percent of the samples contained OE, although clear histological characterization was possible from only 62%. There was no deterioration of UPSIT scores either bilaterally or unilaterally on the side of the biopsy. Patients also maintained the ability to identify individual odorants.


Biopsies of the lower half of the superior turbinate do not affect olfactory function and show strong efficacy in yielding OE tissue and moderate efficacy for yielding tissue appropriate for morphological analysis. Future studies are needed to assess the safety of this procedure in other OE regions.


Smell Immunohistochemistry Smell tests Morphology Nasal mucosa Olfactory function 



The authors thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Araucária for PhD, Post-Doc and PQ for financial support. We especially thank professor Eric H. Holbrook for helping in the final review of the manuscript.

Compliance with ethical standards

Conflicts of interest

Richard L. Doty receives funding from the Michael J. Fox Foundation for Parkinson’s Research. He is a consultant to Acorda Therapeutics, Eisai Co, Ltd, Merck, and Johnson & Johnson. He receives royalties from Cambridge University Press, Johns Hopkins University Press, and John Wiley & Sons, Inc. He is President of, and a major shareholder in, Sensonics International, a manufacturer and distributor of smell- and taste tests. The other authors have no conflicts of interest to disclose.


  1. 1.
    Douek E, Bannister LH, Dodson HC (1975) Recent advances in the pathology of olfaction. Proc R Soc Med 68(8):467–470PubMedPubMedCentralGoogle Scholar
  2. 2.
    Polyzonis BM, Kafandaris PM, Gigis PI, Demetriou T (1979) An electron microscopic study of human olfactory mucosa. J Anat 128(Pt 1):77–83PubMedPubMedCentralGoogle Scholar
  3. 3.
    Moran DT, Rowley JC, Jafek BW (1982) Electron microscopy of human olfactory epithelium reveals a new cell type: the microvillar cell. Brain Res 253(1–2):39–46CrossRefGoogle Scholar
  4. 4.
    Jafek BW (1983) Ultrastructure of human nasal mucosa. Laryngoscope 93(12):1576–1599CrossRefGoogle Scholar
  5. 5.
    Nakashima T, Kimmelman CP, Snow JB, Kimmelman ChP (1984) Structure of human fetal and adult olfactory neuroepithelium. Arch Otolaryngol 110(10):641–646. CrossRefPubMedGoogle Scholar
  6. 6.
    Hasegawa S, Yamagishi M, Nakano Y (1986) Microscopic studies of human olfactory epithelia following traumatic anosmia. Arch Otorhinolaryngol 243(2):112–116. Accessed 5 Dec 2018
  7. 7.
    Yamagishi M, Hasegawa S, Nakano Y (1988) Examination and classification of human olfactory mucosa in patients with clinical olfactory disturbances. Arch Otorhinolaryngol 245(5):316–320CrossRefGoogle Scholar
  8. 8.
    Paik SI, Lehman MN, Seiden AM, Duncan HJ, Smith DV (1992) Human olfactory biopsy. The influence of age and receptor distribution. Arch Otolaryngol Head Neck Surg 118(7):731–738CrossRefGoogle Scholar
  9. 9.
    Moran DT, Jafek BW, Eller PM, Rowley JC (1992) Ultrastructural histopathology of human olfactory dysfunction. Microsc Res Tech 23(2):103–110. CrossRefPubMedGoogle Scholar
  10. 10.
    Winstead W, Marshall CT, Lu CL, Klueber KM, Roisen FJ (2005) Endoscopic biopsy of human olfactory epithelium as a source of progenitor cells. Am J Rhinol 19(1):83–90CrossRefGoogle Scholar
  11. 11.
    Lindsay SL, Johnstone SA, Mountford JC et al (2013) Human mesenchymal stem cells isolated from olfactory biopsies but not bone enhance CNS myelination in vitro. Glia 61(3):368–382. CrossRefPubMedGoogle Scholar
  12. 12.
    Feron F, Perry C, Girard SD, Mackay-Sim A (2013) Isolation of adult stem cells from the human olfactory mucosa. Methods Mol Biol 1059:107–114. CrossRefPubMedGoogle Scholar
  13. 13.
    Twomey JA, Barker CM, Robinson G, Howell DA (1979) Olfactory mucosa in herpes simplex encephalitis. J Neurol Neurosurg Psychiatry 42(11):983–987. Accessed 10 Feb 2017CrossRefGoogle Scholar
  14. 14.
    Arnold SE, Lee EB, Moberg PJ et al (2010) Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease. Ann Neurol 67(4):462–469. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Seiden AM (2004) Postviral olfactory loss. Otolaryngol Clin North Am 37(6 SPEC.ISS.):1159–1166. CrossRefPubMedGoogle Scholar
  16. 16.
    Yee KK, Pribitkin EA, Cowart BJ et al (2010) Neuropathology of the olfactory mucosa in chronic rhinosinusitis. Am J Rhinol Allergy 24(2):110–120. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hummel T, Whitcroft KL, Andrews P et al (2017) Position paper on olfactory dysfunction. Rhinology. CrossRefPubMedGoogle Scholar
  18. 18.
    Féron F, Perry C, McGrath JJ, Mackay-Sim A (1998) New techniques for biopsy and culture of human olfactory epithelial neurons. Arch Otolaryngol Head Neck Surg 124:861–866. CrossRefPubMedGoogle Scholar
  19. 19.
    Wrobel BB, Mazza JM, Evgrafov OV, Knowles JA (2013) Assessing the efficacy of endoscopic office olfactory biopsy sites to produce neural progenitor cell cultures for the study of neuropsychiatric disorders. Int Forum Allergy Rhinol 3(2):133–138. CrossRefPubMedGoogle Scholar
  20. 20.
    Holbrook EH, Rebeiz L, Schwob JE (2016) Office-based olfactory mucosa biopsies. Int Forum Allergy Rhinol. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lovell MA, Jafek BW, Moran DT, Rowley JC 3rd (1982) Biopsy of human olfactory mucosa. An instrument and a technique. Arch Otolaryngol 108(4):247–249CrossRefGoogle Scholar
  22. 22.
    Leopold DA, Hummel T, Schwob JE, Hong SC, Knecht M, Kobal G (2000) Anterior distribution of human olfactory epithelium. Laryngoscope 110(3 Pt 1):417–421. CrossRefPubMedGoogle Scholar
  23. 23.
    Holbrook EH, Wu E, Curry WT, Lin DT, Schwob JE (2011) Immunohistochemical characterization of human olfactory tissue. Laryngoscope 121(8):1687–1701. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Doty RL, Kamath V (2014) The influences of age on olfaction: a review. Front Psychol 5(FEB):1–20. CrossRefGoogle Scholar
  25. 25.
    Lee SH, Lim HH, Park HJ, Lee HM, Choi JO (2000) Olfactory mucosal findings in patients with persistent anosmia after endoscopic sinus surgery. Ann Otol Rhinol Laryngol 109(8 I):720–725CrossRefGoogle Scholar
  26. 26.
    Leopold DA, Hornung DE, Schwob J (1992) Congenital lack of olfactory ability. Ann Otol Rhinal Laryngol 101(3):229–236CrossRefGoogle Scholar
  27. 27.
    Lanza DC, Deems DA, Doty RL et al (1994) The effect of human olfactory biopsy on olfaction—a preliminary-report. Laryngoscope 104(7):837–840CrossRefGoogle Scholar
  28. 28.
    Kern R (2000) Chronic sinusitis and anosmia: pathologic changes in the olfactory mucosa. Laryngoscope 110(7):1071–1077CrossRefGoogle Scholar
  29. 29.
    Lane AP, Gomez G, Dankulich T et al (2002) The superior turbinate as a source of functional human olfactory receptor neurons. Laryngoscope. 112(7 Pt 1):1183–9. Available at: Accessed 03 Aug 2018CrossRefGoogle Scholar
  30. 30.
    Say P, Leopold D, Cochran G et al (2004) Resection of the inferior superior turbinate: does it affect olfactory ability or contain olfactory neuronal tissue? Am J Rhinol 18(3):157–160CrossRefGoogle Scholar
  31. 31.
    Kachramanoglou C, Law S, Andrews P, Li D, Choi D (2013) Culture of olfactory ensheathing cells for central nerve repair: the limitations and potential of endoscopic olfactory mucosal biopsy. Neurosurgery 72(2):170–178. CrossRefPubMedGoogle Scholar
  32. 32.
    Andrews PJ, Poirrier A, Lund VJ et al (2016) Safety of human olfactory mucosal biopsy for the purpose of olfactory ensheathing cell harvest and nerve repair: a prospective controlled study in patients undergoing endoscopic sinus surgery. Rhinology. CrossRefPubMedGoogle Scholar
  33. 33.
    Malnic B, Hirono J, Sato T et al (1999) Combinatorial receptor codes for odors. Cell 96(5):713–723. CrossRefPubMedGoogle Scholar
  34. 34.
    Mombaerts P, Wang F, Dulac C et al (1996) Visualizing an olfactory sensory map. Cell 87(4):675–686. CrossRefPubMedGoogle Scholar
  35. 35.
    Verbeurgt C, Wilkin F, Tarabichi M et al (2014) Profiling of olfactory receptor gene expression in whole human olfactory mucosa. PLoS One 9(5):21–26. CrossRefGoogle Scholar
  36. 36.
    Yamagishi M, Fujiwara M, Nakamura H (1994) Olfactory mucosal findings and clinical course in patients with olfactory disorders following upper respiratory viral infection. Rhinology 32(3):113–118PubMedGoogle Scholar
  37. 37.
    Féron F, Perry C, Hirning MH et al (1999) Altered adhesion, proliferation and death in neural cultures from adults with schizophrenia. Schizophr Res 40(3):211–218CrossRefGoogle Scholar
  38. 38.
    Holbrook EH, Leopold DA, Schwob JE (2005) Abnormalities of axon growth in human olfactory mucosa. Laryngoscope 115(12):2144–2154CrossRefGoogle Scholar
  39. 39.
    Fornazieri MA, dos Santos CA, Bezerra TFP et al (2015) Development of normative data for the Brazilian adaptation of the University of Pennsylvania smell identification test. Chem Senses 40(2):141–149. CrossRefPubMedGoogle Scholar
  40. 40.
    Doty RL (ed) (2009) The smell threshold test administration manual, 2nd edn. Sensonics International, Philadelphia, p 14Google Scholar
  41. 41.
    Altundag A, Salihoglu M, Tekeli H, Saglam M, Cayonu M, Hummel T (2014) Lateralized differences in olfactory function and olfactory bulb volume relate to nasal septum deviation. J Craniofac Surg 25(2):359–362CrossRefGoogle Scholar
  42. 42.
    Damm M, Eckel HE, Jungeholsing M, Hummel T (2003) Olfactory changes at threshold and suprathreshold levels following septoplasty with partial inferior turbinectomy. Ann Otol Rhinol Laryngol 112(1):91–97CrossRefGoogle Scholar
  43. 43.
    Pade J, Hummel T (2008) Olfactory function following nasal surgery. Laryngoscope 118(7):1260–1264CrossRefGoogle Scholar
  44. 44.
    Kilicaslan A, Acar GO, Tekin M, Ozdamar OI (2016) Assessment the long-term effects of septoplasty surgery on olfactory function. Acta Otolaryngol 6489:1–6Google Scholar
  45. 45.
    Kimmelman CP (1994) The risk to olfaction from nasal surgery. Laryngoscope 104:981–988CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ellen Cristine Duarte Garcia
    • 1
  • Ana Carolina Rossaneis
    • 2
  • Alexandre Salvatore Pipino
    • 1
  • Gustavo Vasconcelos Gomes
    • 1
  • Fábio de Rezende Pinna
    • 3
  • Richard Louis Voegels
    • 3
  • Richard L. Doty
    • 4
  • Waldiceu Aparecido VerriJr.
    • 2
  • Marco Aurélio Fornazieri
    • 1
    • 3
    • 5
    Email author
  1. 1.Department of Clinical SurgeryLondrina State University (UEL)LondrinaBrazil
  2. 2.Laboratory of Pain, Inflammation, Neuropathy and Cancer, Department of Pathological SciencesUELLondrinaBrazil
  3. 3.Department of OtorhinolaryngologyUniversity of São PauloSão PauloBrazil
  4. 4.Smell and Taste Center, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of MedicinePontifical Catholic University of ParanáLondrinaBrazil

Personalised recommendations