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Updated: Aug 7, 2026
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Pathological subtype dictates survival and failure pattern in laryngeal neuroendocrine neoplasms: a 15-year
Feifei Qiao1, Na Liu2, He Li3
1Department of Head and Neck Surgery, Shanxi Hospital Affiliated to Cancer Hospital, Cancer Hospital, Shanxi Provincial Cancer Hospital, Chinese Academy of Medical Sciences, Shanxi Medical University, Taiyuan, 031000, China.
Background:
Laryngeal neuroendocrine neoplasms (LNENs) comprise < 1% of laryngeal malignancies, and evidence-based treatment guidelines remain lacking. We sought to delineate clinicopathological features, therapeutic strategies, and survival determinants in a single-institution cohort of consecutive patients with primary LNEN.
Methods:
We retrospectively identified 31 consecutive patients with primary LNEN treated between 2010 and 2024. Histology was centrally reviewed by two head-and-neck pathologists and categorized as well-differentiated neuroendocrine tumor (NET, G1-G3) or poorly differentiated neuroendocrine carcinoma (NEC, small-cell/large-cell). All cases underwent immunohistochemistry (Syn, CgA, Ki-67) and multidisciplinary therapy. Survival analyses were performed with Kaplan-Meier and Cox proportional-hazards models.
Results:
Median age was 60 years, 90.3% were male, and 80.6% had a smoking history. NEC accounted for 71% (22/31) and NET for 29% (9/31). NEC exhibited higher Ki-67 index (85% vs. 10%, P < 0.001), more advanced stage (63.6% vs. 33.3%, P = 0.013), and a predilection for distant metastasis (85.7% vs. 25.0%, P = 0.002). Median overall survival (OS) was 27.0 months for NEC vs. not reached for NET (P < 0.001); 5-year OS was 0% vs. 44.4%. Median disease-free survival (DFS) was 19.0 vs. not reached (P < 0.001). Multivariate analysis identified NEC subtype (HR = 4.23, 95% CI 1.39-12.90), T3-4 stage (HR = 2.61, 95% CI 1.02-6.66), and lymph nodal positivity (HR = 3.12, 95% CI 1.20-8.10) as independent predictors of poor OS; NEC subtype (HR = 3.67, 95% CI 1.15-11.70) and N+ (HR = 3.51, 95% CI 1.22-10.10) predicted inferior DFS. Distant metastasis was the first mode of failure in 68.9% of curative-intent cases.
Conclusions:
Pathologic subtype (NEC vs. NET) emerges as the dominant independent predictor of survival in this cohort. NEC demonstrates a systemic biological phenotype characterized by early distant metastasis. These findings support the hypothesis that intensified perioperative systemic therapy, rather than locoregional escalation, warrants prospective investigation. Multi-center, molecularly stratified trials are needed to establish a precision-medicine paradigm for this rare disease.
