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Background <p>Large cell neuroendocrine carcinoma (LCNEC) of the cervix is an uncommon and highly aggressive tumor. Diagnosis during pregnancy is especially difficult because physiological cervical changes and guideline-based restrictions on excisional procedures may limit detection of invasive disease. When LCNEC is concealed beneath surface adenocarcinoma in situ (AIS), routine punch biopsies may repeatedly miss stromal invasion, resulting in delayed recognition. Such presentations remain rarely documented and warrant attention due to their potential for rapid progression.</p> Case presentation <p>A 28-year-old pregnant woman underwent colposcopy at 20 weeks of gestation for abnormal cervical findings. The first directed punch biopsy demonstrated AIS with high-grade intraepithelial changes. A second colposcopy at 34 weeks showed further enlargement of the visible lesion, yet the repeat punch biopsy again revealed only noninvasive disease. Because excisional diagnosis carries obstetric risks, no excision was performed during pregnancy. After cesarean delivery at 37 weeks, a third colposcopy performed during postpartum cervical involution showed partial resolution of pregnancy-related edema and eversion, although abnormal acetowhite and mosaic patterns persisted. A third postpartum punch biopsy remained noninvasive. Due to persistent discordance between the colposcopic appearance and biopsy results, a diagnostic loop excision was performed at 82 days postpartum. This revealed deeply invasive LCNEC located beneath surface AIS. Staging evaluation showed no residual or metastatic disease. The patient subsequently underwent radical hysterectomy with ovarian preservation and pelvic lymphadenectomy, followed by adjuvant platinum–etoposide chemotherapy, and remains disease-free to date. Review of pregnancy-associated LCNEC cases and population-level survival patterns suggests that earlier diagnosis and definitive treatment are associated with more favorable outcomes, whereas delayed diagnosis or advanced presentation carries markedly poor survival.</p> Conclusions <p>This case shows that invasive LCNEC can remain hidden beneath adenocarcinoma in situ during pregnancy, resulting in repeated false-negative biopsies despite progressive clinical findings. In pregnant patients with persistent mismatch between colposcopic impressions and biopsy results, early postpartum excisional evaluation should be considered to avoid missing an aggressive malignancy.</p>

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Occult cervical large cell neuroendocrine carcinoma masquerading as adenocarcinoma in situ during pregnancy: a case report, literature review, and SEER analysis

  • 期刊论文

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  • 发表日期：

    2026年2月14日

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  • Yifan Hu,
  • Danhui Li,
  • Lihua Qiu,
  • Wen Di

摘要

Background

Large cell neuroendocrine carcinoma (LCNEC) of the cervix is an uncommon and highly aggressive tumor. Diagnosis during pregnancy is especially difficult because physiological cervical changes and guideline-based restrictions on excisional procedures may limit detection of invasive disease. When LCNEC is concealed beneath surface adenocarcinoma in situ (AIS), routine punch biopsies may repeatedly miss stromal invasion, resulting in delayed recognition. Such presentations remain rarely documented and warrant attention due to their potential for rapid progression.

Case presentation

A 28-year-old pregnant woman underwent colposcopy at 20 weeks of gestation for abnormal cervical findings. The first directed punch biopsy demonstrated AIS with high-grade intraepithelial changes. A second colposcopy at 34 weeks showed further enlargement of the visible lesion, yet the repeat punch biopsy again revealed only noninvasive disease. Because excisional diagnosis carries obstetric risks, no excision was performed during pregnancy. After cesarean delivery at 37 weeks, a third colposcopy performed during postpartum cervical involution showed partial resolution of pregnancy-related edema and eversion, although abnormal acetowhite and mosaic patterns persisted. A third postpartum punch biopsy remained noninvasive. Due to persistent discordance between the colposcopic appearance and biopsy results, a diagnostic loop excision was performed at 82 days postpartum. This revealed deeply invasive LCNEC located beneath surface AIS. Staging evaluation showed no residual or metastatic disease. The patient subsequently underwent radical hysterectomy with ovarian preservation and pelvic lymphadenectomy, followed by adjuvant platinum–etoposide chemotherapy, and remains disease-free to date. Review of pregnancy-associated LCNEC cases and population-level survival patterns suggests that earlier diagnosis and definitive treatment are associated with more favorable outcomes, whereas delayed diagnosis or advanced presentation carries markedly poor survival.

Conclusions

This case shows that invasive LCNEC can remain hidden beneath adenocarcinoma in situ during pregnancy, resulting in repeated false-negative biopsies despite progressive clinical findings. In pregnant patients with persistent mismatch between colposcopic impressions and biopsy results, early postpartum excisional evaluation should be considered to avoid missing an aggressive malignancy.