Perineural Invasion (PNI) Definition, Histopathological Parameters of PNI in Oral Squamous Cell Carcinoma With Molecular Insight and Prognostic Significance

Abstract

Oral squamous cell carcinoma is associated with severe morbidity, recurrence of tumor, and reduced survival rate despite advances in treatment. Perineural invasion (PNI) is associated with neurotropic malignancy. PNI is due to the tropism of cancer cells toward nerve bundles in tissue. The aim of this literature review is to study the definition, patterns of PNI, Prognostic and therapeutic significance, and mechanism of PNI along with a molecular insight into oral cavity squamous cell carcinoma. Liebig type A pattern defines PNI as the presence of tumor cells within the peripheral nerve sheath & infiltration into the epineurium, perineurium, or endoneurium. Liebig type B pattern defines PNI as a tumor encircling at least 33% of a nerve. Few studies demonstrated an association between PNI and cervical metastasis which indicate poor prognosis. A higher level of expression of nerve growth factor and tyrosine kinase is associated with PNI in OSCC which can be considered as a biomarker of PNI. PNI needs to be studied in detail as it is associated with the aggressiveness of the tumor and decreased survival.

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

“…Among these, cancer cells, nerve cells (with a predominance of Schwann cells), stromal cells, and fibroblasts have been most rigorously investigated. These cellular entities are central themes in a vast expanse of academic literature, reflecting their significant roles in tumorigenesis and progression [8,12,13]. Contemporary research efforts have pivoted towards elucidating the impact of immune cell infiltration on PNI.…”

“…PNS is a clinical and radiographic phenotype characterized by extensive cancerous growth within and alongside nerves that it becomes identifiable through radiographic imaging [6,7]. In contrast, PNI, the histopathological correlate of PNS, is broadly delineated as the infiltration of cancerous cells into the perineural and intraneural spaces [6][7][8]. Microscopic examination is required to identify PNI, signifying the infiltration of cancer within neural structures.…”

“…PNI occurs frequently across a wide spectrum of cancers and serves as a significant prognostic marker, often heralding aggressive malignancy and correlating with diminished survival rates in a variety of tumors, including those of the head and neck [8], colon [9], prostate [10,11], and pancreas [12,13], etc. When cancer cells exploit the perineural space for growth, following the path of least resistance along nerve fibers, cancer pain was happened [12,14].…”

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

“…The combination of E-cadherin downregulation and MMP overexpression loosens intercellular adhesions, causing the detachment of OSCC cells from the tumor and their centrifugal migration, which will eventually expand the OSCC mass [97].…”