Perineural Invasion and Schwann Cell-Like Phenotypic Changes in Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis.

METHODS: A search for studies was conducted through PubMed, Embase, Scopus, Web of Science, Lilacs, Cochrane, CINAHL (EBSCOhost), and gray literature (Google Scholar), using established screening criteria. The risk of bias was assessed for all articles. Meta-analysis was performed using Review Manager v. 5.3. RESULTS: A total of 2,301 articles were initially identified in the databases, and 25 studies were included. Therefore, 1,437 patients with head and neck ACC were evaluated across five countries. Perineural invasion was categorized as present or absent in most studies (n = 24). The antibodies used to assess phenotypic changes included S100/S100A4, GFAP, SOX-10, Leu-7, NSE, NCAM, HCAM, NGF, BDNF, NT-3, GDNF, TrkA, TrkB, TrkC, P75NTR, GFRα, RET, Notch1, and NICD1. Meta-analysis revealed that the immunoexpression of NGF (p < 0.0001), N-CAM (p = 0.0002), S100/S100A4 (p = 0.0163), and TrkA (p = 0.0175) was higher in ACCs with PNI. Additionally, NGF (p = 0.0237) was increased in ACCs with cribriform/tubular patterns, while N-CAM expression (p = 0.0379) was higher in ACCs with a solid pattern. CONCLUSION: Immunohistochemistry is a technique that can be used to evaluate phenotypic changes. Several markers have been used to suggest Schwann cell-like phenotypic change in PNI of ACC, particularly NGF, N-CAM, S100/S100A4, and TrkA. PROSPERO REGISTRATION: CRD42024504638.