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Background <p>Laryngeal neuroendocrine neoplasms (LNENs) comprise &lt; 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.</p> Methods <p>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.</p> Results <p>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%, <i>P</i> &lt; 0.001), more advanced stage (63.6% vs. 33.3%, <i>P</i> = 0.013), and a predilection for distant metastasis (85.7% vs. 25.0%, <i>P</i> = 0.002). Median overall survival (OS) was 27.0 months for NEC vs. not reached for NET (<i>P</i> &lt; 0.001); 5-year OS was 0% vs. 44.4%. Median disease-free survival (DFS) was 19.0 vs. not reached (<i>P</i> &lt; 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.</p> Conclusions <p>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.</p>

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Pathological subtype dictates survival and failure pattern in laryngeal neuroendocrine neoplasms: a 15-year single-institution experience

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Feifei Qiao,
  • Na Liu,
  • He Li,
  • Meng Zhang,
  • Shubin Dong

摘要

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.