Major salivary gland carcinomas: A 21-center cohort study of 892 patients with external validation of the UICC 9th edition n-classification
In brief
Facial nerve invasion doubles death risk in major salivary gland cancer
In a 21-center study of 892 patients, tumors that infiltrated the facial nerve were about twice as likely to cause death, disease recurrence, or disease-specific mortality compared with nerve-sparing cancers. Intraparotid lymph node spread occurred in nearly 30% of parotid cases and lowered recurrence-free survival, while higher stromal lymphocyte density improved outcomes. These findings highlight the need for routine nerve assessment and refined nodal staging.
- Journal
- Oral oncology (Q1)
- Published
- 11 September 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Pietro De Luca, Giovanni Salzano, Matteo Simone, Gerardo Petruzzi, Filippo Marchi, Marta Filauro, et al.
- PMID
- 42727269
- DOI
- 10.1016/j.oraloncology.2026.108136
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 12 September 2026): Major salivary gland carcinoma cohort with prognostic pathology
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.