Major salivary gland carcinomas: A 21-center cohort study of 892 patients with external validation of the UICC 9th edition n-classification

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.

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Journal
Oral Oncology
Published
2026-09-11
DOI
https://doi.org/10.1016/j.oraloncology.2026.108136
Primary Topic
Salivary Gland Tumors Diagnosis and Treatment
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article

Major salivary gland carcinomas: A 21-center cohort study of 892 patients with external validation of the UICC 9th edition n-classification

Davide Rizzo, Gerardo Petruzzi, Nicoletta Gardenal, Milena Fior et al.
Oral Oncology
Salivary Gland Tumors Diagnosis and Treatment
article

Major salivary gland carcinomas: A 21-center cohort study of 892 patients with external validation of the UICC 9th edition n-classification

Davide Rizzo, Gerardo Petruzzi, Nicoletta Gardenal, Milena Fior, Marco Radici, Giovanni Salzano, Matteo Fermi, Pietro De Luca, Alberto Vito Marcuzzo, Aurelio D’Ecclesia, Marco Ferrari, Giovanni Succo, Giovanni Dell’Aversana Orabona, Teresa Lucante, Arianna Di Stadio, Daniele Marchioni, Claudio Viti, Giuseppe Tortoriello, Francesco Chiari, Alessandra Ruaro, Fabio Ferreli, Teodoro Aragona, Giuseppe Mercante, Francesco Bussu, Marta Filauro, Francesco Antonio Salzano, Angelo Camaioni, Pierre Guarino, Filippo Marchi, Andrea Sacchetto, Luca Gazzini, Francesco Mattioli, Nicola Amato, Alfonso Scarpa, Roberto Saetti, Erika Crosetti, Chiara Alberti, Michael Negrisolo, Alice Azizi Semeskandi, Matteo Simone, Francesco Capuano, Luca Calabrese, Claudio Donadio Caporale, Lazzaro Cassano, Sofia Pangallo, Veronica Scocca, Luigi Falchetta, Luca de Campora, Giuseppe Spriano, Giorgio Peretti, Raul Pellini, Bellini Elisa, Claudia Crescio, Annamaria Ruzza, Giancarlo Tirelli, Elena Mercuri, Markus Thaler
article en

Abstract

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.

Oral OncologyVol. 182
University of Verona (IT), University of Modena and Reggio Emilia (IT), University of Salerno (IT), University of Padua (IT), University of Trieste (IT), Azienda Ospedaliera San Giovanni Addolorata (IT), Casa Sollievo della Sofferenza (IT), Agostino Gemelli University Polyclinic (IT), Mercy Clinic Neurology (US), Ospedale di Bolzano (IT), Ospedale San Carlo (IT), Azienda Ospedaliero Universitaria di Sassari (IT), Ospedale di Santo Spirito (IT), Azienda Sanitaria Locale Viterbo (IT), Azienda USL di Bologna (IT), Ospedale San Giovanni Bosco (IT), Ospedale di Belcolle (IT), Istituti Fisioterapici Ospitalieri (IT), Ospedale Monaldi (IT), Ospedale Policlinico San Martino (IT), Ospedale San Bortolo (IT), IRCCS Humanitas Research Hospital (IT), Link Campus University (IT), University of Naples Federico II (IT), University of Bologna (IT)
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Salivary Gland Tumors Diagnosis and Treatment
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