Background Subclinical local invasion (SLI) beyond radiologically evident margins poses a major challenge in the management of sinonasal and nasopharyngeal malignancies (SNNM). The biological behavior underlying this phenomenon remains poorly characterized, particularly regarding its spatial extent and histology‐dependent patterns. Methods This prospective study included patients undergoing surgical resection of SNNM with intraoperative surgical navigation (SN). Intraoperative biopsies were systematically mapped and spatially correlated with preoperative imaging. Multivariable logistic regression models evaluated the association between positive biopsy probability, distance from the gross tumor surface, and histologic characteristics. Results Fifty‐four patients and 569 biopsies were analyzed; 78 (13.7%) were positive. A significant inverse association between distance from the gross tumor surface and positive biopsy probability was observed, with an approximately 5.1% reduction in odds per millimeter ( p ‐value < 0.001). Histologic type remained independently associated with positive biopsy probability after distance adjustment ( p ‐value < 0.001). Adenoid cystic carcinoma (ACC), squamous cell carcinoma (SCC) with perineural invasion (PNI), other poorly differentiated carcinomas (OPDC), and mesenchymal malignancies showed wider SLI, whereas SCC without PNI, intestinal‐type adenocarcinoma (ITAC), and olfactory neuroblastoma (ONB) demonstrated limited SLI. Tissue‐specific effects were generally limited, although neural tissue was associated with increased positive biopsy probability in ACC. Conclusions SLI in SNNM follows a distance‐dependent pattern with the distance‐invasion relationship varying according to histologic subtype. SN‐based mapping represents a spatially informed strategy to enhance margin assessment and guide histology‐driven surgical and radiotherapy planning. Key Points Navigation‐guided mapping helped to estimate microscopic tumor spread patterns. Subclinical infiltration probability decreases by approximately 5.1% per mm from the tumor margin. Histologic subtype influences the extent of microscopic local invasion. ACC showed the widest microscopic local invasion, followed by SCC with PNI. PNI increased the tumor spread in sinonasal squamous carcinoma.
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Gaudioso et al. (2026) studied this question.
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