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Updated: Jun 19, 2025
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Reconceiving Perineural Invasion in Cutaneous Squamous Cell Carcinoma: From Biological to Histopathological
Filippo Nozzoli1, Romina Nassini2, Francesco De Logu2
1Section of Anatomic Pathology, Department of Health Sciences, University of Florence, Florence, Italy.
Background:
Perineural invasion (PNI) is a complex molecular process histologically represented by the presence of tumor cells within the peripheral nerve sheath and defined when infiltration into the 3 nerve sheath layers can be clearly identified. Several molecular pathways have been implicated in cSCC. PNI is a well-recognized risk factor in cutaneous squamous cell carcinoma (cSCC) and its accurate assessment represents a challenging field in pathology daily practice.
Summary:
As a highly intricate and dynamic process, PNI involves a contingent on bidirectional signaling interactions between the tumor and various nerve components, such as Schwann cells and neurons. The current staging systems recommend the identification of PNI as a dichotomous variable (presence vs. absence) to identify a subgroup of high-risk patients. However, recent further insights revealed that the evaluation of morphological PNI-related features in cSCC may enhance the prognostic stratification of patients and may optimize the current staging guidelines for recurrence risk assessment and improvement of patient selection for postoperative adjuvant treatments. Furthermore, recent emerging biomarkers could redefine early PNI detection.
Key Messages:
This review provides updated insights into cSCC with PNI, focusing on molecular and cellular pathogenic processes, and aims to increase knowledge on prognostic relevant PNI-related histological features.
