ReviewPerineural invasion in adenoid cystic carcinoma of the salivary glands: A valid prognostic indicator?
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.
References (80)
- et al.
Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases
Am J Surg
(1974) - et al.
Perineural lymphatics: myth or fact
Am J Surg
(1966) - et al.
The dissemination of the tumors of the head and neck via the cranial nerves
Radiol Clin North Am
(1970) - et al.
The significance of perineural spread in adenoid cystic carcinoma of the major and minor salivary glands
Int J Oral Maxillofac Surg
(1988) - et al.
Adenoid cystic carcinoma of the head and neck – a 20 years experience
Int J Oral Maxillofac Surg
(2004) - et al.
Malignant tumors of the submaxillary gland
Am J Surg
(1973) - et al.
Adenoid cystic carcinoma of the salivary glands. A study of 93 cases
Am J Surg
(1979) - et al.
Adenoid cystic carcinoma. Analysis of 50 cases
Oral Surg
(1976) - et al.
Adenoid cystic carcinoma of major and minor salivary glands
Am J Surg
(1971) - et al.
Adenoid cystic carcinoma of the submandibular gland: a 35 year review
Otolaryngol Head Neck Surg
(2004)
Flow cytometric evaluation of adenoid cystic carcinoma: comparison with histologic subtype and survival
Am J Surg
Malignant tumors of intraoral minor salivary glands
Oral Oncol
The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation
Int J Radiat Oncol Biol Phys
Malignant parotid tumors: presentation, clinical/pathologic prognostic factors, and treatment outcomes
Int J Radiat Oncol Biol Phys
Adenoid cystic carcinoma of the head and neck treated by surgery with or without post-operative radiation therapy: prognostic features of recurrence
Int J Radiat Oncol Biol Phys
Intraoral adenoid cystic carcinoma: prognostic factors and outcome
Oral Oncol
Stage means more than grade in adenoid cystic carcinoma
Am J Surg
Neural cell adhesion molecule in adenoid cystic carcinoma invading the skull base
Otolaryngol Head Neck Surg
Adenoid cystic carcinoma of the maxillary antrum
Am J Otolaryngol
Report of one hundred tumors of the minor salivary glands
Am J Surg
Minor salivary gland tumours of the oral cavity. A review of 68 cases
Oral Surg
Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands
Int J Oral Maxillofac Surg
Adenoid cystic carcinoma of the major and minor salivary glands. A clinicopathological study of 17 cases
J Maxfac Surg
Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature
Oral Oncol
Prognostic factors in head and neck adenoid cystic carcinoma
Oral Oncol
The importance of clinical staging of minor salivary gland carcinoma
Am J Surg
Risk factors for local recurrence of adenoid cystic carcinoma: the role of postoperative radiation therapy
Am J Otolaryngol
Adenoid cystic carcinoma of the head and neck
Br J Plast Surg
Adenoid cystic carcinoma of intra-oral minor salivary glands
Oral Oncol
Outcomes and prognostic variables in adenoid cystic carcinoma of the head and neck: a recent experience
Int J Radiat Oncol Biol Phys
Atlas of tumor pathology tumors of the salivary glands
Adenoid cystic carcinoma
Perineural spread of head and neck tumors: how accurate is MR imaging?
AJNR Am J Neuroradiol
Flow cytometric DNA content of adenoid cystic carcinoma of submandibular gland
Archs Otolaryngol Head Neck Surg
Intraoral adenoid cystic carcinoma. The presence of perineural spread in relation to site, size, local extension, and metastatic spread in 22 cases
Cancer
The controversial adenoid cystic carcinoma. The implications of histological grade and perineural invasion
Imaging of perineural tumor spread from palatal carcinoma
AJNR Am J Neuroradiol
Adenoid cystic carcinoma of the parotid gland
Acta Radiol Ther Phys Biol
Surgical management of tumors of intraoral salivary glands
Cancer
Adenoid cystic salivary gland carcinoma. A histopathological review of treatment failure patterns
Cancer
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