Pietro De Luca, Giovanni Salzano, Matteo Simone, Gerardo Petruzzi, Filippo Marchi, Marta Filauro, Bellini Elisa, Matteo Fermi, Nicola Amato, Andrea Sacchetto, Elena Mercuri, Milena Fior, Veronica Scocca, Chiara Alberti, Pierre Guarino, Francesco Chiari, Alessandra Ruaro, Michael Negrisolo, Luca Gazzini, Markus Thaler, Nicoletta Gardenal, Alberto Vito Marcuzzo, Teodoro Aragona, Annamaria Ruzza, Luigi Falchetta, Alice Azizi Semeskandi, Sofia Pangallo, Francesco Capuano, Luca de Campora, Francesco Mattioli, Fabio Ferreli, Claudia Crescio, Davide Rizzo, Alfonso Scarpa, Teresa Lucante, Erika Crosetti, Giorgio Peretti, Giuseppe Mercante, Claudio Donadio Caporale, Arianna Di Stadio, Aurelio D'Ecclesia, Daniele Marchioni, Giancarlo Tirelli, Lazzaro Cassano, Giovanni Dell'Aversana Orabona, Luca Calabrese, Marco Ferrari, Roberto Saetti, Giovanni Succo, Francesco Antonio Salzano, Giuseppe Spriano, Giuseppe Tortoriello, Raul Pellini, Francesco Bussu, Claudio Viti, Marco Radici, Angelo Camaioni
Histological facial nerve infiltration was the most consistently independent prognostic factor, supporting systematic pathological reporting. Current TNM N-staging may inadequately capture intraparotid lymph node involvement, and sTILs showed a continuous prognostic effect on RFS, supporting prospective biomarker validation.
OBJECTIVES: Major salivary gland carcinomas are rare malignancies with limited prognostic evidence. This study assessed survival outcomes, independent prognostic factors, intraparotid lymph node involvement, and stromal tumor-infiltrating lymphocyte (sTIL) density.
MATERIALS AND METHODS: Multicenter retrospective cohort study of 892 patients, classified per the 2022 WHO Classification, treated surgically at 21 Italian referral centers (2010-2023).
RESULTS: Median follow-up 61.4 months. The cohort included 61.1% males, median age 59.0 years; parotid gland was the primary site in 90.4%. AdCC (28.4%) and MEC (27.2%) were most frequent; 63.8% at Stage I-II. Five-year OS, DSS, and RFS were 87.9% (95% CI 85.4-90.1%), 93.1% (91.0-94.8%), and 77.7% (74.6-80.4%). Histological facial nerve infiltration was the most robust independent prognostic factor across all endpoints (OS: HR 1.78, 95% CI 1.12-2.81; DSS: HR 2.49, 1.37-4.50; RFS: HR 2.22, 1.54-3.21). Age, lymphovascular invasion, and atypical mitoses were additional independent predictors. Among 688 parotid patients with intraparotid nodal data available, 29.2% had intraparotid metastasis; 60.7% lacked cervical involvement, with LN+/pN0 patients showing worse RFS than LN-negative patients (71.2% vs 85.3%; p = 0.002). In 285 patients with available sTIL assessment (32.0%), higher sTIL density predicted improved RFS (HR 0.51 per 10% increment, 95% CI 0.35-0.73; p < 0.001). UICC 9th edition restaging reclassified 27.3% of pN0 patients as node-positive, with significant survival stratification (p < 0.001).
CONCLUSIONS: Histological facial nerve infiltration was the most consistently independent prognostic factor, supporting systematic pathological reporting. Current TNM N-staging may inadequately capture intraparotid lymph node involvement, and sTILs showed a continuous prognostic effect on RFS, supporting prospective biomarker validation.