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Purpose <p>The clinical and pathological characteristics of nasopharyngeal neuroendocrine carcinoma (NNEC) remain poorly defined, and its association with Epstein-Barr virus (EBV) remains not well established.</p> Methods <p>We conducted a retrospective analysis of patients with pathologically confirmed NNEC treated between 2013 and 2024. Clinical, pathological, and treatment data were collected, including histology, immunophenotyping, plasma EBV DNA levels, and imaging features. Survival endpoints were overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).</p> Results <p>Among 15 patients (12 males, 3 females; median age 51 years), 12 were EBV-positive. Lymph node metastasis was frequently observed at baseline (15/15, 100%), characterized by involvement of the retropharyngeal lymph node (RPN) (10/15, 66.7%) and at level II (14/15, 93.3%) and followed by an orderly caudal progression without skip metastasis. Following treatment, 14 patients (93.3%) achieved a complete response. After a median follow-up of 44 months, the 3-year OS, PFS, and DMFS rates were 77.4%, 50.5%, and 50.5%, respectively; the median OS and PFS were both 72 months, whereas DMFS was not reached. Distant metastases developed in 7 patients (46.7%), most commonly in the liver, bone, and brain. Among patients with detectable EBV DNA at baseline, complete EBV DNA clearance was achieved in 11 of these 12 patients (91.7%), and 6 of 7 patients with disease progression exhibited a concomitant exponential rise in EBV DNA levels.</p> Conclusion <p>NNEC exhibits an orderly pattern of cervical lymph node metastasis. Plasma EBV DNA level is a promising dynamic biomarker for treatment response and disease surveillance in EBV-positive NNEC. Despite the high initial complete response rate, the considerable risk of distant metastasis contributes to compromised long-term survival, underscoring the need for novel therapeutic strategies.</p>

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Clinical-radiopathological features and EBV DNA dynamics in nasopharyngeal neuroendocrine carcinoma: implications for prognosis and surveillance

  • 期刊论文

  • 发表日期：

    2026年3月28日

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  • Huilan Chen,
  • Daqiang Huang,
  • Xinlan Chen,
  • Zhiwei Yan,
  • Jingyu Zhu,
  • Yuan Huang,
  • Shaojun Lin,
  • Lifang Chen,
  • Hanchuan Xu

摘要

Purpose

The clinical and pathological characteristics of nasopharyngeal neuroendocrine carcinoma (NNEC) remain poorly defined, and its association with Epstein-Barr virus (EBV) remains not well established.

Methods

We conducted a retrospective analysis of patients with pathologically confirmed NNEC treated between 2013 and 2024. Clinical, pathological, and treatment data were collected, including histology, immunophenotyping, plasma EBV DNA levels, and imaging features. Survival endpoints were overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).

Results

Among 15 patients (12 males, 3 females; median age 51 years), 12 were EBV-positive. Lymph node metastasis was frequently observed at baseline (15/15, 100%), characterized by involvement of the retropharyngeal lymph node (RPN) (10/15, 66.7%) and at level II (14/15, 93.3%) and followed by an orderly caudal progression without skip metastasis. Following treatment, 14 patients (93.3%) achieved a complete response. After a median follow-up of 44 months, the 3-year OS, PFS, and DMFS rates were 77.4%, 50.5%, and 50.5%, respectively; the median OS and PFS were both 72 months, whereas DMFS was not reached. Distant metastases developed in 7 patients (46.7%), most commonly in the liver, bone, and brain. Among patients with detectable EBV DNA at baseline, complete EBV DNA clearance was achieved in 11 of these 12 patients (91.7%), and 6 of 7 patients with disease progression exhibited a concomitant exponential rise in EBV DNA levels.

Conclusion

NNEC exhibits an orderly pattern of cervical lymph node metastasis. Plasma EBV DNA level is a promising dynamic biomarker for treatment response and disease surveillance in EBV-positive NNEC. Despite the high initial complete response rate, the considerable risk of distant metastasis contributes to compromised long-term survival, underscoring the need for novel therapeutic strategies.