Introduction

1. Olfactory neuroblastoma (ONB. The alternative name is esthesioneuroepithelioma) is estimated to comprise approximately 3% of nasal neoplasms excluding benign polyps. The incidence in North America/Western Europe is estimated to be approximately 0.15/million/year. There is no evidence for a sex difference in incidence. It occurs in all ages (but is rare below 10 year and over 70 year).¹ It has been reported to have bimodal incidence, with peaks in the 2nd -3rd decade and later in the 6th and 7th decades of life.² It has also been estimated there have only been 950 cases cited in the scientific literature from 1924, when ONB was first cited in the literature, up to 1997.³ Thus the available evidence suggests that ONB is a very rare tumour.

2. ONB is described as a neuroectodermal neoplasm showing predominantly neural features.⁴ The most common symptoms in patients presenting with ONB are nasal obstruction (93%), epistaxis (55%) and rhinorrhea (30%). Other symptoms such as headache and anosmia occur at an incidence of below 10%.² Diagnoses is based on clinical presentation, CT/MRI* screening and histology with the need for a battery of immunohistochemical stains to differentiate from other closely related head and neck cancers.^5,6,7

[* Computerised Topography/Magnetic Resonance Imaging]

Published information: Association of ONB with occupation or chemical exposure

3. There is no published evidence to associate ONB with any particular occupation or chemical exposure. The only published case-report of ONB where an occupational exposure aetiology has been suggested refers to a woodworker exposed to wood dust for 25 years.⁸ The Committee was aware that adenocarcinoma of the nasal cavities and paranasal sinuses is clearly associated with exposure to hard wood dust. The published evidence on wood dust had been thoroughly reviewed by the World Health Organisation’s International Agency for Research on Cancer (IARC) in 1995 and no evidence for an association between exposure to wood dust (hard or softwoods) and ONB had been documented.⁹ The Committee agreed that it was highly improbable that the researchers investigating wood workers would have misdiagnosed ONB as adenocarcinoma of the sinuses.

Association of ONB with dentists/dental nurses

Presentation from Professor Valerie Lund (Institute of Laryngology and Otolaryngology)

4. Professor Lund presented details of four individuals with ONB, two of whom had worked as dentists, and two who had been employed as dental nurses. Members heard that two pathologists had independently verified the diagnoses. Full details of these case reports have been submitted to a peer reviewed journal.

COC discussion

5. Members reviewed the available information and considered the data on the case-series held by the Institute of Laryngology and Otolaryngology in the context of information identifiable though the Office for National Statistics (England and Wales) for the past 10 years. No dentists of dental nurses had been identified in the limited review of ONS data. Members acknowledged that details of occupation were underreported to ONS. The Committee felt that there was no evidence of referral bias of dentists/dental nurses to the Institute. The Committee agreed that the finding of 4 dentists/dental nurses with ONB out of a series of 52 cases of ONB referred to the Institute over a period of 23 years was likely to be a statistically significant association.

6. The Committee considered available information on potential chemical exposures of dentists/dental nurses (eg to metallic mercury, oil of cloves (principle ingredient eugenol) and methymethacrylate) (a copy of the covering paper can be found on http://www.advisorybodies.doh.gov.uk/pdfs/cc0337.pdf). It was agreed that there was no evidence to associate exposure to these chemicals with ONB in dentists/dental workers.

7. The Committee noted a report of cytogenetic damage in nasal tissue from dental technicians.¹⁰ It was agreed that dental technicians were a separate and distinct group from dentists/dental nurses with regard to chemical exposures. Thus data from dental technicians was not helpful in identifying relevant chemical exposures of dentists/dental nurses.

8. The Committee considered that the first priority for further work would be to consider additional epidemiological investigations to confirm the finding reported by the Institute of Laryngology and Otolaryngology. This might include evaluation of case-reports of ONB from other countries or detailed evaluation of information held by centres of excellence (for head and neck tumours) and pathology departments from the UK, Europe and elsewhere.

COC Conclusion

9. The Committee concluded that the finding of 4 dentists/dental nurses with ONB by the Institute of Laryngology and otolaryngology was likely to be a statistically significant association. Additional epidemiological data are needed to substantiate this observation. No definite conclusions on the potential association between dentists/dental nurses and olfactory neuroblastoma can be reached at this point in time.

May 2004

References

1. Henk JM (1996). Uncommon tumours of the head and neck region Chapter 6.11 in volume 1 of the Oxford textbook of Oncology, edited by Peckham M, Pinedo H and Veronesi U. Oxford University Press, Oxford, pp1059-1064.

2. Lund VJ et al (2003). Olfactory neuroblastoma: Past, present and future. The Laryngoscope, 113, 502-507.

3. Brioch G, Paglairi A and Ottaviani F (1997). Estesioneuroblastoma: A general review of the cases published since the discovery of the tumour in 1924. Anticancer Research, 17, 2683-2706.

4. Mill SE (2002). Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Modern pathology, 15, 264-278.

5. Lund VJ and Milroy C (1993). Olfactory neuroblastoma: Clinical and pathological aspects. Rhinology, 31, 1-6.

6. Zhao SP and Zhou XF (2002). Co-expression of trkA snd p75 neurotrophin receptor in extracranial olfactory neuroblastoma cells. Neuropathology and Applied neurobiology, volume 28, 301-307.

7. Prado GL etla (2001). Olfactory Neuroblastoma visualised by Technetium –99-m-ECD SPECT. Radiation Medicine, 19, 267-270.

8. Magnavita N et al (2003). Aesthesioneuroblastoma in a woodworker. Occupational Medicine, 53, 231-234.

9. IARC (1995). International Agency for Research on Cancer. Monographs on the Evaluation of carcinogenic risk of chemicals to man. Wood dust and formaldehyde, volume 62, p 35. ISBN 92 832 12 622.

10. Burgaz S et al (2002). Assessment of cytogenetic damage in lymphocytes and in exfoliated nasal cells of dental laboratory technicians exposed to chromium, cobalt and nickel. Mutation Research, 521, 47-56.

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