Perineural Spread in Noncutaneous Head and Neck Cancer: New Insights into an Old Problem

Abstract

Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell carcinoma and adenoid cystic carcinoma are the most commonly involved tumors. The most commonly involved nerves are the trigeminal (cranial nerve [CN] V) and facial (CN VII) and their branches. Neural spread away from a tumor is encountered less often and usually causes specific symptoms such as pain, muscle weakness, and atrophy, depending on the involved nerves. While clinical symptoms and physical examination may suggest the presence of neural invasion, specific imaging modalities such as fat-suppressed T1-weighted magnetic resonance images, should be utilized to identify perineural tumor spread in its early phases. Perineural tumor spread should be considered and addressed in the treatment planning of patients with head and neck or skull base cancers as it can influence the extent of surgery, and the dosage and fields of radiation therapy. In the current review, we discuss the clinical course of perineural tumor spread and its therapeutic implications.

Significance of perineural invasion in locally advanced bucco alveolar complex carcinomas treated with surgery and postoperative radiation ± concurrent chemotherapy

“…Some pathologists report tumors in close proximity to nerves and at least one‐third of the nerve circumference as PNI. However, a recent study suggests that tumor invasion into any nerve layer or nerve sheath as clinically relevant PNI . In addition, detection of PNI in a specimen is challenging because of processing artifacts or inadequate specimen assessment leading to false‐negative reporting .…”

“…However, a recent study suggests that tumor invasion into any nerve layer or nerve sheath as clinically relevant PNI. 17 In addition, detection of PNI in a specimen is challenging because of processing artifacts or inadequate specimen assessment leading to falsenegative reporting. 18 Although PNI is seen in small peripheral nerves histologically and is clinically silent, perineural spread is the tumor spread along larger nerves clinically or is radiologically evident and often symptomatic.…”

Defining the Prevalence and Prognostic Value of Perineural Invasion and Angiolymphatic Invasion in Human Papillomavirus–Positive Oropharyngeal Carcinoma

“…Although the literature describes a more conclusive role for PNI in prognosis, supplementary data could contribute to discussions about the use of PNI (and perhaps ALI) to guide postsurgical treatment. 17,22,23 …”

Prognostic factors and survival in adenoid cystic carcinoma of the sinonasal cavity

“…We demonstrated a decrease in both OS and DFS when large named nerves were involved on univariate analysis. 25,26 As it seems that microscopic perineural invasion is not reliably associated with survival, future studies may emphasize the prognostic significance of these 2 variables. 13,21 It has been suggested that microscopic perineural invasion loses prognostic significance due to the use of postoperative radiotherapy to sterilize residual microscopic tumor.…”

“…13 Although not analyzed in this study, the authors recognize that perineural spread, distinguished from perineural invasion by gross disease spread along nerves, and intraneural invasion have been associated with worse survival. 25,26 As it seems that microscopic perineural invasion is not reliably associated with survival, future studies may emphasize the prognostic significance of these 2 variables.…”