Multifocal Perineural Invasion Predicts Poor Disease-Free Survival in Early-Stage Tongue Squamous Cell Carcinoma Exhibiting WPOI-4.

OBJECTIVES

Perineural invasion (PNI) is a pathological hallmark associated with tumor spread. Evidence suggested that PNI location (extratumoural vs. intratumoural) held prognostic significance in early-stage oral squamous cell carcinoma (OSCC), whereas the prognostic impact of PNI extent (unifocal versus multifocal) remained to be elucidated. The primary aim of this study was to evaluate the prognostic relevance of PNI extent in early-stage tongue squamous cell carcinoma (TSCC) characterized by worst pattern of invasion 4 (WPOI-4).

MATERIALS AND

METHODS

A total of 130 patients with pT1/T2 pN0/Nx TSCC were included in this retrospective study, of whom 104 did not receive postoperative radiotherapy (PORT), while the remaining 26 underwent PORT. Based on the Yamauchi-Kuratomi (YK) classification, WPOI-4 cases were further stratified into 4C/4D and non-4C/4D subtypes. Depth of invasion (DOI) was dichotomized using a 4 mm threshold.

RESULTS

Multivariate analysis revealed that both multifocal and unifocal PNI were significantly associated with disease-free survival (DFS), whereas no meaningful association was observed with overall survival (OS). Compared to unifocal PNI (odds ratio [OR] = 5.504; 95% confidence interval (CI) = 1.994-15.188; p < 0.001), multifocal PNI conferred an approximately fivefold increased risk of disease progression (OR = 27.009; 95% CI = 8.695-83.900; p < 0.001). In addition, multifocal PNI showed a notable correlation with DOI > 4 mm and 4C/4D histology. Elective neck dissection (END) combined with postoperative radiotherapy (PORT) significantly reduced disease progression in PNI-positive patients, particularly those with multifocal PNI (OR = 0.01; 95% CI = 0.002-0.051; p < 0.001). Among patients who did not receive PORT, END showed limited benefit in multivariate analysis. However, after excluding cases with isolated local recurrence, END was associated with improved DFS in patients with cervical lymph node metastasis (CLNM) (p = 0.017).

CONCLUSION

These findings support incorporating the extent of PNI into routine pathology reporting and suggest that END and PORT may be considered, particularly in cases of multifocal PNI.