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The two-hit hypothesis and paraganglioma of the head and neck

Published online by Cambridge University Press:  06 June 2017

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Abstract

Type
Editorial
Copyright
Copyright © JLO (1984) Limited 2017 

The article on management of head and neck paragangliomaReference Harrison and Corbridge 1 in this month's Journal of Laryngology & Otology is being published on the first anniversary (10 July 2017) of the passing away of Alfred G Knudson, the architect of the two-hit theory,Reference Knudson 2 fundamental to our understanding of tumour genetic mutation. This theory explained, for the first time, among other matters, why some develop a tumour early in life and others late. As tumours are the result of accumulated mutations to a cell's DNA,Reference Nordling 3 it follows that one born with a single mutation needs a second ‘hit’ for a tumour to occur, and another born without mutation requires two hits, reflecting a play betwixt germ line and somatic mutation. We honour Alfred G Knudson (born 1923), who worked at the Fox Chase Cancer Centre Philadelphia, for his work that led to the concept of tumour suppressor genes.

As our understanding of head and neck paraganglioma increases, we realise that surgery, which has long been the mainstay of treatment, is no longer so. This is not to say that surgery is out, but management is tempered by advances in genetics, improvements in diagnostic imaging and the longitudinal behaviour of these tumours.Reference Moore, Netterville, Mendenhall, Isaacson and Nussenbaum 4 A quarter of patients with head and neck paragangliomas harbour predisposing genetic mutations.Reference Persu, Hamoir, Grégoire, Garin, Duvivier and Reychler 5 SDHD mutations were found in all patients with familial head and neck paraganglioma in a paper from Belgium.Reference Persu, Hamoir, Grégoire, Garin, Duvivier and Reychler 5 In sporadic cases, the prevalence of SDHB mutations was twice that of SDHD mutations. Patients harbouring SDHB mutations had unilateral late-onset head and neck tumours, without evidence of recurrence or malignancy.

The work by Harrison and Corbridge,Reference Harrison and Corbridge 1 on active surveillance of head and neck paragangliomas over a five-year period, demonstrates the favourable outcome of avoiding surgery. Although the numbers are small, the paper is a useful addition to existing literature and relevant to our circumstances.

Chan and colleague's paper,Reference Chan, Siou, Welch and Powell 6 on the association of pre-operative oxygen saturation as a predictor of future need for paediatric intensive care in children who undergo supraglottoplasty for laryngomalacia, is a first such study from the UK. This has implications for a number of other procedures undertaken in children with potential airway issues.

Lou and LouReference Lou and Lou 7 reviewed the application of moist agents to the edge of traumatic tympanic membrane perforations; they show that it shortens closure times and improves closure rates. This is not in keeping with traditional teaching to leave traumatic perforations of the eardrum alone. Jellinge et al.Reference Jellinge, Kristensen and Larsen 8 had previously shown a 97 per cent closure rate through a policy of simple watchful waiting.

References

1 Harrison, L, Corbridge, R. Active surveillance management of head and neck paragangliomas: case series and review of the literature. J Laryngol Otol 2017;131:580–4Google Scholar
2 Knudson, A. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971;68:820–3Google Scholar
3 Nordling, C. A new theory on cancer-inducing mechanism. Br J Cancer 1953;7:6872 Google Scholar
4 Moore, MG, Netterville, JL, Mendenhall, WM, Isaacson, B, Nussenbaum, B. Head and neck paragangliomas: an update on evaluation and management. Otolaryngol Head Neck Surg 2016;154:597605 CrossRefGoogle ScholarPubMed
5 Persu, A, Hamoir, M, Grégoire, V, Garin, P, Duvivier, E, Reychler, H et al. High prevalence of SDHB mutations in head and neck paraganglioma in Belgium. J Hypertens 2008;26:1395–401CrossRefGoogle ScholarPubMed
6 Chan, S, Siou, G, Welch, A, Powell, S. Predictors for routine admission to paediatric intensive care for post-supraglottoplasty laryngomalacia patients. J Laryngol Otol 2017;131:640–4Google Scholar
7 Lou, ZC, Lou, ZH. A moist edge environment aids the regeneration of traumatic tympanic membrane perforations. J Laryngol Otol 2017;131:564–71Google Scholar
8 Jellinge, ME, Kristensen, S, Larsen, K. Spontaneous closure of traumatic tympanic membrane perforations: observational study. J Laryngol Otol 2015;129:950–4Google Scholar