Perineural Invasion and Perineural Tumor Spread in Head and Neck Cancer

Int J Radiat Oncol Biol Phys. 2019 Apr 1;103(5):1109-1124. doi: 10.1016/j.ijrobp.2018.12.009. Epub 2018 Dec 15.


Perineural invasion (PNI), the neoplastic invasion of nerves, is a common pathologic finding in head and neck cancer that is associated with poor clinical outcomes. PNI is a histologic finding of tumor cell infiltration and is distinct from perineural tumor spread (PNTS), which is macroscopic tumor involvement along a nerve extending from the primary tumor that is by definition more advanced, being radiologically or clinically apparent. Despite widespread acknowledgment of the prognostic significance of PNI and PNTS, the mechanisms underlying its pathogenesis remain largely unknown, and specific therapies targeting nerve invasion are lacking. The use of radiation therapy for PNI and PNTS can improve local control and reduce devastating failures at the skull base. However, the optimal volumes to be delineated with respect to targeting cranial nerve pathways are not well defined, and radiation can carry risks of major toxicity secondary to the location of adjacent critical structures. Here we examine the pathogenesis of these phenomena, analyze the role of radiation in PNI and PNTS, and propose guidelines for radiation treatment design based on the best available evidence and the authors' collective experience to advance understanding and therapy of this ominous cancer phenotype.

Publication types

  • Review

MeSH terms

  • Carcinoma, Adenoid Cystic / diagnostic imaging
  • Carcinoma, Adenoid Cystic / pathology*
  • Carcinoma, Adenoid Cystic / radiotherapy*
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Head and Neck Neoplasms / diagnostic imaging
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Lingual Nerve / diagnostic imaging
  • Lingual Nerve / pathology
  • Magnetic Resonance Imaging / methods
  • Mouth Mucosa / innervation
  • Mouth Mucosa / pathology
  • Myelin Sheath / pathology
  • Nasopharynx / innervation
  • Nasopharynx / pathology
  • Neoplasm Invasiveness
  • Palate, Hard / innervation
  • Palate, Hard / pathology
  • Parotid Gland / diagnostic imaging
  • Parotid Gland / innervation
  • Parotid Gland / pathology
  • Peripheral Nervous System / diagnostic imaging
  • Peripheral Nervous System / pathology*
  • Prognosis
  • Radiation Injuries / pathology
  • Radiotherapy Dosage
  • Submandibular Gland / diagnostic imaging
  • Submandibular Gland / innervation
  • Submandibular Gland / pathology
  • Tongue / innervation
  • Tongue / pathology