Elsevier

Oral Oncology

Volume 45, Issue 11, November 2009, Pages 936-940
Oral Oncology

Review
Perineural invasion in adenoid cystic carcinoma of the salivary glands: A valid prognostic indicator?

https://doi.org/10.1016/j.oraloncology.2009.07.001Get rights and content

Summary

Of malignant tumours with a propensity to invade the perineural space, adenoid cystic carcinoma of the salivary glands is perhaps the best known. However, it is not known if microscopic evidence of perineural invasion has true prognostic significance in adenoid cystic carcinoma. A review of the available data, which is the aim of this article, reveals the issue is not straightforward. There is a plethora of conflicting data which, on balance, suggest the answer is indeed in the affirmative, particularly if the nerve involved is above a certain size, or “named”. Even if the data are equivocal, many head and neck surgeons and oncologists take account of histologically proved perineural invasion when planning treatment for adenoid cystic carcinoma.

Introduction

Adenoid cystic carcinoma (ACC) comprises approximately 4% of all epithelial salivary neoplasms, 1% of all head and neck malignancies and 7.5–10% of all salivary malignancies.1, 2, 3 It is defined by the World Health Organisation (WHO) as “a basaloid tumour consisting of epithelial and myoepithelial cells in various morphological configurations, including tubular, cribriform and solid patterns. It has a relentless clinical course and usually a fatal outcome”.3 They also attest to “the propensity of these tumours for perineural invasion. Facial nerve paralysis may also occur” and that ACC “can extend along nerves for a considerable distance beyond the clinically apparent boundaries of the tumour”. Despite this, the WHO conclude that the “influence of perineural invasion (PNI) on survival has been contradictory”. This is perhaps surprising, as neurotropism and spread by PNI would seem a reasonable explanation for the propensity of ACC to recur locally, or present with distant metastasis as a result of occult extension beyond apparently clear resection margins. What is the evidence that PNI does, or does not, affect the prognosis of patients with ACC? The aim of this review is to provide a digest of the available data and answer this question. Although ACC can affect exocrine glands at almost any anatomical site, this article will only consider tumours of the salivary glands.

Section snippets

Data on PNI from clinicopathological series of ACC

PNI occurs via contiguous spread along perineural spaces, or within the nerve itself, since it is unlikely that perineural lymphatics exist.4 A distinction has been made between PNI and perineural spread, the former being a microscopic feature of malignancy often confined to the main tumour mass, the latter the clinico-radiological observation of distant spread via perineural spaces, or within the neural sheath and nerve itself.5 Large primary ACC, those of advanced clinical stage and recurrent

Additional considerations

Although a characteristic of ACC, PNI can of course occur in any malignant neoplasm. One series of head and neck squamous cell carcinomas revealed that 27% of such tumours may invade nerves.71 About 89% of these were of oral, laryngeal or pharyngeal origin. The phenomenon is also commonly seen in polymorphous low grade adenocarcinoma, a tumour that, at worst, recurs locally or spreads to local lymph nodes.72 Perhaps PNI is a more important finding in tumours with which is it not so

Conclusions

The answer to the question posed at the beginning of this article, “does histological evidence of PNI affect the patient’s prognosis?” is, in some series anyway, certainly “yes”. There is no consensus that PNI correlates with site, histological grade or other clinicopathological variables. However, the majority of studies show PNI to be an adverse factor for one or more outcome indicators. Even in the face of equivocal findings, microscopic PNI suggests a clinico-radiological investigation of

Conflict of interest statement

None declared.

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