Skip to main content

Advertisement

Log in

Noninvasive histological imaging of head and neck squamous cell carcinomas using confocal laser endomicroscopy

  • Head and Neck
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Confocal laser endomicroscopy (CLE) is an imaging technique that uses miniaturized fiberoptic probes to allow real-time histological imaging of human tissue. An application of CLE in otorhinolaryngology has hardly been investigated so far. In our study, we analyzed the applicability of CLE to visualize cancerous and healthy tissue of the head and neck region. Formalin-fixed tissue specimens from 135 head and neck squamous cell carcinoma (HNSCC) patients and 50 healthy controls were investigated using CLE with and without topical application of acriflavine. Four head and neck surgeons, four pathologists, and four laymen evaluated the CLE images of the HNSCC cases regarding the tumor localization and its border to healthy tissue. The tumor localization and the tumor border were correctly identified in 97 % by the pathologists, 85 % by the head and neck surgeons, and 70 % by the laymen. The main difference in evaluation results was seen in the correct identification of the tumor site (p < 0.05), while there was no significant difference in the identification of the tumor border. CLE is a valuable tool for real-time histological imaging of HNSCCs. It can help to visualize the tumor border and, thereby, facilitate a more precise tumor surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    Article  CAS  PubMed  Google Scholar 

  2. Marur S, Forastiere AA (2008) Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc 83:489–501

    Article  PubMed  Google Scholar 

  3. Chiesa F, Mauri S, Tradati N, Calabrese L, Giugliano G, Ansarin M, Andrle J, Zurrida S, Orecchia R, Scully C (1999) Surfing prognostic factors in head and neck cancer at the millenium. Oral Oncol 35:590–596

    Article  CAS  PubMed  Google Scholar 

  4. Goetz M (2012) Confocal Laser Endomicroscopy: Applications in clinical and translational science—a comprehensive review. ISRN Pathol. doi:10.5402/2012/387145

    Google Scholar 

  5. Wallace MB, Sharma P, Lightdale C, Wolfsen H, Coron E, Buchner A, Bajbouj M, Bansal A, Rastogi A, Abrams J, Crook JE, Meining A (2010) Preliminary accuracy and interobserver agreement for the detection of intraepithelial neoplasia in Barrett’s esophagus with probe-based confocal laser endomicroscopy. Gastrointest Endosc 72:19–24

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wallace MB, Meining A, Canto MI, Fockens P, Miehlke S, Roesch T, Lightdale CJ, Pohl H, Carr-Locke D, Löhr M, Coron E, Filoche B, Giovannini M, Moreau J, Schmidt C, Kiesslich R (2010) The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther 31:548–552

    Article  CAS  PubMed  Google Scholar 

  7. Polglase AL, McLaren WJ, Skinner SA, Kiesslich R, Neurath MF, Delaney PM (2005) A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. Gastrointest Endosc 62:686–695

    Article  PubMed  Google Scholar 

  8. Kiesslich R, Burg J, Vieth M, Gnaendiger J, Enders M, Delaney P, Polglase A, McLaren W, Janeli D, Thomas S, Nafe B, Galle PR, Neurath MF (2004) Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 127:706–713

    Article  PubMed  Google Scholar 

  9. Goetz M, Ziebart A, Foersch S, Vieth M, Waldner MJ, Delaney P, Galle PR, Neurath MF, Kiesslich R (2010) In vivo molecular imaging of colorectal cancer with confocal endomicroscopy by targeting epidermal growth factor receptor. Gastroenterology 138:435–446

    Article  CAS  PubMed  Google Scholar 

  10. Foersch S, Kiesslich R, Waldner MJ, Delaney P, Galle PR, Neurath MF, Goetz M (2010) Molecular imaging of VEGF in gastrointestinal cancer in vivo using confocal laser endomicroscopy. Gut 59:1046–1055

    Article  PubMed  Google Scholar 

  11. Meining A, Saur D, Bajbouj M, Becker V, Peltier E, Höfler H, von Weyhern CH, Schmid RM, Prinz C (2007) In vivo histopathology for detection of gastrointestinal neoplasia with a portable, confocal miniprobe: an examiner blinded analysis. Clin Gastroenterol Hepatol 5:1261–1267

    Article  PubMed  Google Scholar 

  12. Carlson K, Pavlova I, Collier T, Descour M, Follen M, Richards-Kortum R (2005) Confocal microscopy: imaging cervical precancerous lesions. Gynecol Oncol 99(3 Suppl 1):S84–S88

    Article  PubMed  Google Scholar 

  13. Tan J, Quinn MA, Pyman JM, Delaney PM, McLaren WJ (2009) Detection of cervical intraepithelial neoplasia in vivo using confocal endomicroscopy. BJOG 116:1663–1670

    Article  CAS  PubMed  Google Scholar 

  14. Wiesner C, Jäger W, Salzer A, Biesterfeld S, Kiesslich R, Hampel C, Thüroff JW, Goetz M (2011) Confocal laser endomicroscopy for the diagnosis of urothelial bladder neoplasia: a technology of the future? BJU Int 107:399–403

    Article  PubMed  Google Scholar 

  15. Sonn GA, Jones SN, Tarin TV, Du CB, Mach KE, Jensen KC, Kiao JC (2009) Optical biopsy of human bladder neoplasia with in vivo confocal laser endomicroscopy. J Urol 128:1299–1305

    Article  Google Scholar 

  16. Fuchs FS, Zirlik S, Hildner K, Schubert J, Vieth M, Neurath MF (2013) Confocal laser endomicroscopy for diagnosing lung cancer in vivo. Eur Respir J 41:1401–1408

    Article  PubMed  Google Scholar 

  17. Lane PM, Lam S, McWilliams A, Leriche JC, Anderson MW, Macaulay CE (2009) Confocal fluorescence microendoscopy of bronchial epithelium. J Biomed Opt. doi:10.1117/1.3103583

    PubMed Central  Google Scholar 

  18. Thiberville L, Moreno-Swirc S, Vercauteren T, Peltier E, Cavé C, Bourg Heckly G (2007) In vivo imaging of the bronchial wall microstructure using fibered confocal fluorescence microscopy. Am J Respir Crit Care Med 175:22–31

    Article  PubMed  Google Scholar 

  19. Snuderl M, Wirth D, Sheth SA, Bourne SK, Kwon CS, Ancukiewicz M, Curry WT, Frosch MP, Yaroslavsky AN (2013) Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors. Brain Pathol 23:73–81

    Article  PubMed  Google Scholar 

  20. Charalampaki P, Javed M, Daali S, Heiroth HJ, Igressa A, Weber F (2015) Confocal laser endomicroscopy for real-time histomorphological diagnosis: our clinical experience with 150 brain and spinal tumor cases. Clin Neurosurg 62(Suppl 1):171–176

    Article  Google Scholar 

  21. Abbaci M, Breuskin I, Casiraghi O, De Leeuw F, Ferchiou M, Temam S, Laplace-Builhé C (2014) Confocal laser endomicroscopy for non-invasive head and neck cancer imaging: a comprehensive review. Oral Oncol 50:711–716

    Article  PubMed  Google Scholar 

  22. Volgger V, Conderman C, Betz CS (2013) Confocal laser endomicroscopy in head and neck cancer: steps forward? Curr Opin Otolaryngol Head Neck Surg 21:164–170

    Article  PubMed  Google Scholar 

  23. White WM, Rajadhyaksha M, González S, Fabian RL, Anderson RR (1999) Noninvasive imaging of human oral mucosa in vivo by confocal reflectance microscopy. Laryngoscope 109:1709–1717

    Article  CAS  PubMed  Google Scholar 

  24. Clark AL, Gillenwater AM, Collier TG, Alizadeh-Naderi R, El-Naggar AK, Richards-Kortum RR (2003) Confocal microscopy for real-time detection of oral cavity neoplasia. Clin Cancer Res 9:4714–4721

    PubMed  Google Scholar 

  25. Just T, Stave J, Boltze C, Wree A, Kramp B, Guthoff RF, Pau HW (2006) Laser scanning microscopy of the human larynx mucosa: a preliminary, ex vivo study. Laryngoscope 116:1136–1141

    Article  PubMed  Google Scholar 

  26. Abbaci M, Temam S, Casiraghi O, Vielh P, Bosq J, Fouret P, Laplace-Builhé C (2009) Characterization of laryngeal carcinoma by confocal endomicroscopy. Head Neck Oncol 1(Suppl 1):O14. doi:10.1186/1758-3284-1-S1-O14

    Article  Google Scholar 

  27. Muldoon TJ, Roblyer D, Williams MD, Stepanek VM, Richards-Kortum R, Gillenwater AM (2012) Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope. Head Neck 34:305–312

    Article  PubMed  Google Scholar 

  28. Vila PM, Park CW, Pierce MC, Goldstein GH, Levy L, Gurudutt VV, Polydorides AD, Godbold JH, Teng MS, Genden EM, Miles BA, Anandasabapathy S, Gillenwater AM, Richards-Kortum R, Sikora AG (2012) Discrimination of benign and neoplastic mucosa with a high-resolution microendoscope (HRME) in head and neck cancer. Ann Surg Oncol 19:3534–3539

    Article  PubMed  PubMed Central  Google Scholar 

  29. Farahati B, Stachs O, Prall F, Stave J, Guthoff R, Pau HW, Just T (2010) Rigid confocal endoscopy for in vivo imaging of experimental oral squamous intraepithelial lesions. J Oral Pathol Med 39:318–327

    PubMed  Google Scholar 

  30. Zheng W, Harris M, Kho KW, Thong PS, Hibbs A, Olivo M, Soo KC (2004) Confocal endomicroscopic imaging of normal and neoplastic human tongue tissue using ALA-induced-PPIX fluorescence: a preliminary study. Oncol Rep 12:397–401

    PubMed  Google Scholar 

  31. Thong PS, Kho KW, Zheng W, Harris M, Soo KC, Olivo M (2007) Development of a laser confocal endomicroscope for in vivo fluorescence imaging. J Mech Med Biol. doi:10.1142/S0219519407002108

    Google Scholar 

  32. Thong PS, Olivo M, Kho KW, Zheng W, Mancer K, Harris M, Soo KC (2007) Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity. J Biomed Opt 12:014007

    Article  PubMed  Google Scholar 

  33. Maitland KC, Gillenwater AM, Williams MD, El-Naggar AK, Descour MR, Richards-Kortum RR (2008) In vivo imaging of oral neoplasia using a miniaturized fiber optic confocal reflectance microscope. Oral Oncol 44:1059–1066

    Article  PubMed  PubMed Central  Google Scholar 

  34. Haxel BR, Goetz M, Kiesslich R, Gosepath J (2010) Confocal endomicroscopy: a novel application for imaging of oral and oropharyngeal mucosa in human. Eur Arch Otorhinolaryngol 267:443–448

    Article  PubMed  Google Scholar 

  35. Pogorzelski B, Hanenkamp U, Goetz M, Kiesslich R, Gosepath J (2012) Systematic intraoperative application of confocal endomicroscopy for early detection and resection of squamous cell carcinoma of the head and neck: a preliminary report. Arch Otolaryngol Head Neck Surg 138:404–411

    Article  PubMed  Google Scholar 

  36. Thong PS, Tandjung SS, Movania MM, Chiew WM, Olivo M, Bhuvaneswari R, Seah HS, Lin F, Qian K, Soo KC (2012) Toward real-time virtual biopsy of oral lesions using confocal laser endomicroscopy interfaced with embedded computing. J Biomed Opt. doi:10.1117/1.JBO.17.5.056009

    Google Scholar 

  37. Pierce MC, Schwarz RA, Bhattar VS, Mondrik S, Williams MD, Lee JJ, Richards-Kortum R, Gillenwater AM (2012) Accuracy of in vivo multimodal optical imaging for detection of oral neoplasia. Cancer Prev Res (Phila) 5:801–809

    Article  Google Scholar 

  38. Just T, Pau HW (2013) Intra-operative application of confocal endomicroscopy using a rigid endoscope. J Laryngol Otol 127:599–604

    Article  CAS  PubMed  Google Scholar 

  39. Contaldo M, Poh CF, Guillaud M, Lucchese A, Rullo R, Lam S, Serpico R, MacAulay CE, Lane PM (2013) Oral mucosa optical biopsy by a novel handheld fluorescent confocal microscope specifically developed: technologic improvements and future prospects. Oral Surg Oral Med Oral Pathol Oral Radiol 116:752–758

    Article  PubMed  Google Scholar 

  40. Nathan CAO, Kaskas NM, Ma X, Chaudhery S, Lian T, Moore-Medlin T, Shi R, Mehta V (2014) Confocal laser endomicroscopy in the detection of head and neck precancerous lesions. Otolaryngol Head Neck Surg 151:73–80

    Article  PubMed  Google Scholar 

  41. Cooper JS, Porter K, Mallin K, Hoffman HT, Weber RS, Ang KK, Gay EG, Langer CJ (2009) National cancer database report on cancer of the head and neck: 10-year update. Head Neck 31:748–758

    Article  PubMed  Google Scholar 

  42. Barnes L, Eveson JW, Reichart P, Sidransky D (2005) Pathology and genetics of head and neck tumors. World Health Organization Classification of Tumors. IARC Press, Lyon

  43. Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB (2003) Cancer incidence in five continents, vol VIII. IARC Press, Lyon

    Google Scholar 

  44. Shahid MW, Crook JE, Meining A, Perchant A, Buchner A, Gomez V, Wallace MB (2011) Exploring the optimal fluorescein dose in probe-based confocal laser endomicroscopy for colonic imaging. Interv Gastroenterol 1:166–171

    Article  Google Scholar 

  45. Burleson GR, Caulfield MJ, Pollard M (1979) Ozonation of mutagenic and carcinogenic polyarmoatic amines and polyaromatic hydrocarbons in water. Cancer Res 39:2149–2154

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Samira Daali, Mehreen Javed, Ulrike Bechtel and Monika Hoffmann for their excellent technical assistance. This study was supported by a HOMFORexzellent grant to M.L. and by Siemens AG.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maximilian Linxweiler.

Ethics declarations

Conflicts of interest

This study was funded by a HOMFOR grant to M.L. and Siemens AG. Both sponsors had no influence on the study design, the collection, analysis and interpretation of data, writing of the report, and the decision to submit the article for publication.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Linxweiler, M., Kadah, B.A., Bozzato, A. et al. Noninvasive histological imaging of head and neck squamous cell carcinomas using confocal laser endomicroscopy. Eur Arch Otorhinolaryngol 273, 4473–4483 (2016). https://doi.org/10.1007/s00405-016-4145-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-016-4145-8

Keywords

Navigation