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

Abstract

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.

Background

Large cell neuroendocrine carcinoma (LCNEC) of the cervix is an extremely uncommon malignancy, representing a small fraction of cervical neuroendocrine carcinomas [1–3]. Owing to its rapid growth, early metastatic potential, and absence of standardized diagnostic pathways, timely identification remains difficult. These challenges are amplified during pregnancy, when physiological cervical changes and conservative management guidelines for high-grade intraepithelial lesions limit diagnostic interventions. As a result, invasive disease may be missed despite repeated evaluation.

False-negative biopsies of invasive cervical cancer during pregnancy have been reported, but LCNEC concealed beneath coexisting intraepithelial lesions has rarely been documented. The combination of surface adenocarcinoma in situ (AIS) or high-grade squamous intraepithelial lesion (HSIL) overlying a deeply seated high-grade neuroendocrine carcinoma can produce persistent sampling discordance, complicating both recognition and decision-making.

We present a case of postpartum-diagnosed cervical LCNEC following three antepartum biopsies showing only AIS and HSIL. To contextualize the diagnostic pitfalls and therapeutic implications, we reviewed published cases of LCNEC during pregnancy and examined population-level outcomes from the Surveillance, Epidemiology, and End Results (SEER) database. These complementary sources illustrate the consequences of delayed diagnosis and highlight the need for cautious interpretation of biopsy results in pregnant patients presenting with discordant clinical and pathological findings.

Case presentation

Patient information and antenatal course

A 28-year-old gravida 2 para 0 woman presented for routine prenatal care. Cervical cytology and human papillomavirus (HPV) testing were performed at 20 weeks’ gestation as part of the initial comprehensive evaluation after the patient transferred antenatal care to our center from her hometown. She tested positive for high-risk HPV-16, although liquid-based cytology (TCT) was negative. Colposcopic examination revealed significant abnormalities: the anterior cervical lip displayed dense acetowhite epithelium with coarse mosaicism and atypical vessels, while the posterior lip featured a nodular excrescence with dense acetowhitening, collectively suggestive of HSIL (Fig. 1A). Subsequent biopsy, however, revealed adenocarcinoma in situ (AIS) accompanied by focal high-grade squamous intraepithelial lesion (HSIL/cervical intraepithelial neoplasia [CIN]2). Serum tumor markers—including CA125, CA199, HE4, squamous cell carcinoma antigen (SCC-Ag), and carcinoembryonic antigen (CEA)—were within normal limits, while alpha-fetoprotein (AFP) was physiologically elevated due to pregnancy.

Fig. 1.

Serial colposcopic findings demonstrating the evolution of the cervical lesion during pregnancy and the postpartum period. A Colposcopy at 20 weeks of gestation reveals dense acetowhite epithelium with coarse mosaicism and atypical vessels on the anterior lip. The posterior lip features a nodular excrescence with dense acetowhitening. B At 34 weeks of gestation, the lesion shows significant progression. The anterior lip retains coarse mosaicism, while the nodular lesion on the posterior lip (6–8 o’clock) has markedly enlarged into an exophytic mass with denser acetowhitening, highly suspicious for invasion. C Postpartum colposcopy at 67 days reflects cervical involution and hormonal withdrawal. The exophytic lesion on the posterior lip has largely regressed or retracted. However, the anterior lip persistently displays dense acetowhite epithelium and coarse mosaicism, suggestive of HSIL but lacking definitive macroscopic signs of the underlying invasive carcinoma. Abbreviations: HSIL, high-grade squamous intraepithelial lesion

Conservative management with close surveillance was adopted. At 34 weeks’ gestation, a follow-up colposcopy revealed significant progression: the anterior lip retained coarse mosaicism, while the neoplastic growth at the 6–8 o’clock position on the posterior lip had markedly enlarged with denser acetowhitening (Fig. 1B). Although these features strongly raised the suspicion of invasive carcinoma, a repeat biopsy remained discordant, again confirming only persistent AIS and HSIL (CIN2), accompanied by a TCT result of atypical squamous cells of undetermined significance (ASCUS). A Multidisciplinary Team (MDT) meeting was convened at 35 weeks to address this diagnostic discrepancy. Given that the pregnancy was approaching term, the consensus was to defer intervention slightly and schedule delivery at 38 weeks, followed by rigorous postpartum re-evaluation. However, spontaneous premature rupture of membranes occurred at 37 weeks while the patient was residing in her hometown, necessitating emergency Cesarean section at a local hospital. Both mother and neonate recovered uneventfully.

Postpartum diagnosis and pathological assessment

Following delivery, the patient remained in her hometown for postpartum recovery, leading to delayed surveillance. After returning to our center 67 days postpartum, repeat evaluation was undertaken. Colposcopy reflected the physiological impact of hormonal withdrawal and cervical involution: the previously edematous and everted transformation zone had retracted, and the exophytic excrescence on the posterior lip had largely regressed. Consequently, only the anterior lip exhibited dense acetowhitening with coarse mosaicism, suggestive of HSIL but lacking distinct signs of frank invasion (Fig. 1C). Despite this apparent macroscopic improvement, biopsy continued to show AIS and HSIL (CIN2–3). Pelvic magnetic resonance imaging (MRI) demonstrated an irregular cervical canal with focal stromal thinning but preserved continuity and no areas of diffusion restriction. Given the persistent high-grade surface lesions and the concern that the regressed posterior lesion might have retracted into the canal (masking occult invasive disease), a diagnostic loop electrosurgical excision procedure (LEEP) combined with fractional curettage was performed at 82 days postpartum.

The procedure yielded the definitive diagnosis. Histopathological examination of the LEEP specimen revealed a biphasic lesion located primarily at the 5 o’clock and 9–12 o’clock positions. The superficial mucosa exhibited AIS admixed with HSIL (CIN3), whereas the underlying stroma contained a sharply circumscribed invasive component with a depth of stromal invasion of 3.5 mm and a horizontal extent of 5 mm, consistent with FIGO stage IA2 (pT1a2). No lymphovascular space invasion was identified (Fig. 2A–C). This invasive component was initially classified as poorly differentiated carcinoma. Crucially, the endocervical, ectocervical, and basal surgical margins were free of tumor. Furthermore, endocervical curettage yielded benign glandular epithelium, and endometrial curettage showed proliferative phase endometrium, effectively ruling out an endometrial primary.

Fig. 2.

Histopathology and immunohistochemistry of the LEEP specimen. A Low-power H&E section (1.5×) revealing the distinct biphasic architecture. Yellow arrows indicate the deeply invasive LCNEC component in the stroma; Red arrow points to the superficial AIS; Blue arrow marks the coexisting HSIL. B High-power magnification (40×) of the LCNEC component, characterized by solid nests of large polygonal cells with prominent nucleoli and mitotic activity. C High-power magnification (40×) of the superficial AIS component. D–F High-power views (40×) demonstrating diffuse positive staining for neuroendocrine markers INSM1 (D), chromogranin A (E), and synaptophysin (F) in the LCNEC tumor cells. G Ki-67 staining (40×) reveals a markedly elevated proliferation index (approx. 70%) in the LCNEC component. H Low-power view (1.5×) of p16 immunohistochemistry showing strong, diffuse block-type positivity in both the superficial AIS/HSIL and deep LCNEC components. I CK7 staining highlights the divergent differentiation: positive in the glandular AIS component but negative in the LCNEC component. Abbreviations: H&E, hematoxylin and eosin; LCNEC, large cell neuroendocrine carcinoma; AIS, adenocarcinoma in situ; HSIL, high-grade squamous intraepithelial lesion; INSM1, insulinoma-associated protein 1; CK7, cytokeratin 7

Based on the characteristic histomorphology, immunohistochemistry subsequently confirmed the invasive component as LCNEC. The tumor consisted of large polygonal cells with abundant eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, brisk mitotic activity, and extensive necrosis. The tumor showed diffuse positivity for INSM1, synaptophysin, and chromogranin A. The Ki-67 proliferation index was approximately 70%. p16 showed strong block-type positivity in both AIS and LCNEC areas, whereas CK7 was positive in the AIS component but largely negative in LCNEC, emphasizing the divergent histologic origins (Fig. 2D–I). p40 and p63 positivity was confined to the HSIL component, while the invasive carcinoma was diagnosed based on morphology and diffuse neuroendocrine marker expression.

Staging and therapeutic interventions

Post-LEEP positron emission tomography (PET) showed inflammatory changes without definite residual tumor (Fig. 3). Preoperative neuron-specific enolase (NSE) levels remained within the normal range.

Fig. 3.

Postoperative PET-CT Imaging. Representative coronal, sagittal, and axial fused PET-CT images. The scan, performed 96 days postpartum and 2 weeks following diagnostic LEEP, reveals an irregular nodular focus with intense radiotracer uptake at the cervical os (crosshairs), measuring approximately 19 × 15 mm with an SUVmax of 6.8. The uptake was interpreted as most consistent with postoperative inflammatory change rather than definite residual malignancy. Abbreviations: PET-CT, positron emission tomography-computed tomography; LEEP, loop electrosurgical excision procedure; SUVmax, maximum standardized uptake value

At 96 days postpartum, a second MDT meeting reaffirmed the aggressive nature of LCNEC. Considering the patient’s young age and the rarity of ovarian metastasis in early-stage cervical neuroendocrine carcinoma (NEC), ovarian preservation was considered safe. At 101 days postpartum, the patient underwent laparoendoscopic single-site (LESS) radical hysterectomy (type C1), bilateral salpingectomy, and pelvic lymphadenectomy. Final pathology showed no residual carcinoma in the uterus or lymph nodes. The disease was staged as FIGO 2018 stage IA2.

Adjuvant treatment and follow-up

Given the high-grade neuroendocrine histology, adjuvant chemotherapy was recommended despite early-stage disease. The patient initiated EP chemotherapy (etoposide 160 mg d1–3 plus cisplatin 110 mg d1). After 4 cycles, she briefly hesitated due to quality-of-life concerns, but a third MDT meeting strongly recommended completion of therapy. She ultimately completed 6 cycles at 8 months postpartum.

After completion of adjuvant chemotherapy, the patient entered a structured surveillance program. During the first two years, follow-up is scheduled at 3-month intervals and includes pelvic examination, HPV testing and cervical cytology from the vaginal cuff, as well as lower abdominal imaging (CT or ultrasound). Although serum tumor markers were assessed at follow-up and were within normal limits, they are not planned for routine longitudinal surveillance due to the lack of validated markers in cervical LCNEC. At the most recent follow-up (15 months postpartum; 7 months after chemotherapy), the patient remained disease-free. At that visit, serum tumor markers, TCT, HPV testing, and abdominopelvic imaging (computed tomography [CT] and ultrasound) showed no evidence of recurrence.

Discussion and conclusions

This case exemplifies a diagnostic failure mode in pregnancy-associated cervical evaluation, in which deeply invasive LCNEC remains occult despite repeated colposcopic assessment and biopsy, and differs from previously reported cases in several critical aspects. Diagnostic delay in this patient was not incidental but structurally driven by three interrelated factors. First, the tumor displayed a distinct biphasic architecture, with AIS/HSIL confined to the surface epithelium masking a sharply circumscribed, deeply invasive neuroendocrine component. Given the sampling plane of routine punch biopsy, such deeply embedded foci beneath intraepithelial lesions are structurally inaccessible, rendering repeated surface-directed biopsies intrinsically insufficient. Second, pregnancy-associated cervical edema and eversion altered lesion visibility and accessibility, resulting in fluctuating colposcopic appearances that did not reliably correspond to the underlying pathology. Third, the spatial mismatch between biopsy sites and the eventual invasive foci identified in the LEEP specimen underscores the limitations of targeted sampling in heterogeneous or multifocal disease. Importantly, postpartum involution and macroscopic improvement further obscuted residual invasive disease, compounding the diagnostic challenge. It should be clarified that HPV testing at 20 weeks’ gestation in the present case did not represent routine second-trimester screening at our institution, but rather completion of baseline cervical screening after transfer of care from another region without complete prior screening records [4].

Retrospective immunohistochemical staining of the initial punch biopsy specimens was considered; however, the limited tissue volume and absence of morphologic features suspicious for neuroendocrine carcinoma precluded meaningful additional staining. Although p40 and p63 are commonly regarded as squamous lineage markers, focal positivity has been reported in high-grade neuroendocrine carcinomas and should not preclude this diagnosis. In the present case, the diagnosis of LCNEC was established based on characteristic morphology in conjunction with neuroendocrine markers (INSM1, synaptophysin, and chromogranin A), rather than lineage markers alone [5].

To contextualize these diagnostic pitfalls and their therapeutic implications, we performed a comprehensive, multi-step literature search across PubMed, Embase, Web of Science, Google Scholar, and CNKI databases. The search strategy was iterative: First, specific keywords including “large cell neuroendocrine carcinoma” combined with “pregnancy” or “postpartum” were used to identify core cases. Second, the search was broadened to “cervical neuroendocrine carcinoma” to capture cases where the specific histologic subtype was clarified only in the full text (identifying one additional case). Third, reference lists of retrieved articles were manually screened (“snowballing”) to detect cases where the obstetric context was not evident in the title (identifying one case diagnosed 6 weeks postpartum). After excluding duplicates (including a case reported in both Chinese and English), 8 historical cases of pregnancy- or postpartum-associated cervical LCNEC were identified and synthesized with the present case (Table 1). Two distinct clinical trajectories emerged. Patients diagnosed at advanced stages exhibited rapid disease progression and poor outcomes despite aggressive multimodal therapy, whereas those diagnosed after definitive excisional procedures were predominantly early-stage and achieved favorable long-term disease control following radical surgery and adjuvant chemotherapy. Notably, cases lacking diagnostic excision were more likely to be diagnosed at an advanced stage, highlighting the central role of diagnostic excision in determining disease stage and prognosis. The EP regimen (etoposide plus platinum) was the predominant chemotherapy backbone among reported survivors. Fetal outcomes largely reflected gestational age at diagnosis, with iatrogenic preterm delivery frequently undertaken to facilitate maternal treatment. Given the limited number of reported cases, these observations should be interpreted as descriptive and hypothesis-generating rather than causal [1, 6, 7].

Table 1.

Summary of 9 cases of cervical LCNEC during pregnancy

Case	Age (y)	FIGO Stage	Tumor Size	HPV/Markers	Diagnosis Timing	Pregnancy Outcome	Treatment Details	Follow-up
1 [15]	30	IIIC1r	8 cm	HPV 18+ ASCUS	3rd trimester (35 wks)	Immediate delivery (CS at 35 wks)	CS → EP ×2 → CCRT (Complication: SIADH) Recurrence: Immunotherapy + Chemo	DOD (OS: 20 mo)
2 [16]	29	IB2	3 cm	HPV 18+ AFP ↑	2nd trimester (16 wks)	Pregnancy preservation (CS at 35 wks)	NACT (EP ×2) → CS + RH + BS + Ovarian Biopsy + SLNB → Adjuvant EP ×4	NED (19 mo)
3 [17]	26	IB2	6 cm	HPV + AFP ↑	1 st trimester (13 wks)	Pregnancy termination (D&E at 13 wks)	RH + BS + Ovarian Suspension + PLND → Adjuvant EP ×1 (ongoing)	Survival data unavailable (Early report)
4 [18]	31	IB1	1.8 cm	N/A	3rd trimester (32 wks)	Pregnancy preservation (Vaginal delivery at 39 wks)	Vaginal Delivery → RH + PLND → Adjuvant EP ×4	NED (11 mo)
5 [19]	34	IIA1	4 cm	HPV 18+	2nd trimester (21 wks)	Pregnancy preservation (CS at 31 wks)	NACT (EP ×3) → CS + RH + BSO + PLND → Adjuvant CCRT ×5	NED (38 mo)
6 [20]	30	IIB	5 cm	N/A	2nd trimester (18 wks)	Pregnancy termination (Induced abortion at 18 wks)	Pregnancy Termination → CCRT ×3 + Chemo ×3	NED (21 mo)
7 [21]	26	IVB	7 cm (Liver met 15 cm)	HPV 18+	3rd trimester (30 wks)	Immediate delivery (CS at 31 wks)	CS → Palliative Chemo ×8 (EP/Paclitaxel + Nedaplatin + Bevacizumab)	DOD (OS: 12 mo)
8 [22]	33	IB1	1.2–2 cm	N/A	Postpartum (6 wks)*	N/A	RH + BSO + PLND → Adjuvant EP ×5	NED (24 mo)
9 (current case)	28	IA2	0.5 cm	HPV 16+ ASCUS AFP ↑	2nd trimester (24 wks; detected during pregnancy, confirmed postpartum) **	Pregnancy preservation (CS at 37 wks)	CS → delayed RH + BS + SLNB (IA2, 0.35 cm) → Adjuvant EP ×6	NED (11 mo)

Abbreviations: GA Gestational Age, CS Cesarean Section, RH Radical Hysterectomy, BS Bilateral Salpingectomy, BSO Bilateral Salpingooophorectomy, PLND Pelvic Lymph Node Dissection, SLNB Sentinel Lymph Node Biopsy, PE Platinum (Cisplatin/Carboplatin) + Etoposide, NACT Neoadjuvant Chemotherapy, D&E Dilation and Evacuation, CCRT Concurrent Chemoradiotherapy, NED No Evidence of Disease, DOD Died of Disease, OS Overall Survival

^*Case 8 was diagnosed 6 weeks postpartum, likely developed during pregnancy

^**In the current case, definitive pathologic staging was confirmed postpartum at 9 weeks after delivery

To further contextualize these case-based observations at the population level, we analyzed data from the SEER Program (SEER*Stat 9.0.42.0) [8]. The study queried the ‘Incidence - SEER Research Limited-Field Data, 21 Registries’ (November 2024 submission), covering the period from 2000 to 2022. Inclusion criteria were restricted to primary malignant tumors of the cervix uteri. Histological subtypes were identified using International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) codes: LCNEC (8013/3), small cell neuroendocrine carcinoma (SCNEC; 8041/3–8045/3), and squamous cell carcinoma (SCC; 8052/3–8086/3). Overall survival was estimated using the SEERStat built-in survival function, which provides unadjusted Kaplan–Meier estimates. Multivariable adjustment for covariates such as age, treatment modality, or chemotherapy was not feasible due to limitations of registry-level data and the scope of the present analysis. These data place cervical LCNEC within the survival spectrum of high-grade neuroendocrine carcinomas, with outcomes indistinguishable from small-cell counterparts (Table 2).

Table 2.

Survival outcomes of cervical LCNEC, SCNEC, and SCC stratified by SEER summary stage (SEER database 2000–2022)

	LCNEC	SCNEC	Total NEC	SCC
No. of Patients	144	1,125	1,688	77,216
Median OS (months)	17.4	19.3	17.9	> 60
5-Year OS	26.7%	30.3%	29.1%	65.6%
Localized	55.2%	60.0%	57.8%	88.4%
Regional-DE	33.3%	37.0%	34.0%	57.9%
Regional-LN	35.7%	42.3%	47.1%	70.3%
Regional-Both	17.9%	26.0%	22.8%	51.2%
Distant	7.6%	8.9%	9.1%	19.0%

Data Source: Surveillance, Epidemiology, and End Results (SEER) Program (SEER*Stat 9.0.42.0); Database: Incidence - SEER Research Limited-Field Data, 21 Registries (excluding IL), Nov 2024 Submission (2000–2022). Selection Criteria: Primary Site: Cervix Uteri. Behavior: Malignant. Histology Codes (ICD-O-3): LCNEC: 8013/3. SCNEC: 8041/3, 8042/3, 8043/3, 8044/3, 8045/3. NEC (Total): Includes LCNEC, SCNEC, and Neuroendocrine carcinoma, NOS (8246/3). SCC: 8052/3, 8053/3, 8054/3, 8070/3, 8071/3, 8072/3, 8073/3, 8074/3, 8075/3, 8076/3, 8077/3, 8078/3, 8084/3, 8085/3, 8086/3.

Abbreviations: LCNEC Large cell neuroendocrine carcinoma, SCNEC Small cell neuroendocrine carcinoma, NEC Neuroendocrine carcinoma, SCC Squamous cell carcinoma, OS Overall survival, Regional-DE Regional by direct extension only, Regional-LN Regional lymph nodes involved only, Regional-Both Regional by both direct extension and lymph node involvement

While registry-based analyses are limited by the absence of centralized pathology review and detailed treatment data, the lack of any observable survival advantage supports managing LCNEC with the same level of oncologic caution as other high-grade neuroendocrine malignancies [9, 10]. Early surgical resection remains central for localized disease, while systemic platinum-based chemotherapy is extrapolated from treatment paradigms across organ systems [2, 7]. Pregnancy does not attenuate oncologic aggressiveness; rather, gestational age primarily influences the timing of definitive intervention. Although the antepartum pathological diagnosis in this case was AIS, the patient exhibited persistent and progressive colposcopic features highly suspicious for invasive disease, with repeated clinicopathological discordance and no feasible option for diagnostic excision during pregnancy. Management was therefore guided by principles applicable to suspected invasive cervical malignancy, in which pregnancy may be preserved to achieve fetal maturity when immediate oncologic treatment is not feasible, and cesarean delivery is often recommended to facilitate prompt postpartum definitive management [2, 11]. Confirmed advanced-stage disease, by contrast, requires urgent multimodal therapy irrespective of gestational age.

Ovarian preservation was considered acceptable in this case given the early-stage disease (FIGO IA2), absence of lymphovascular space invasion, and lack of gross ovarian involvement. Emerging retrospective data suggest that in early-stage neuroendocrine carcinoma of the cervix (tumor size ≤ 4 cm without nodal involvement), the incidence of ovarian metastasis is relatively low, and may be as low as approximately 4% for tumors ≤ 2 cm [12]. In addition, the 2025 Expert Consensus on the Diagnosis and Treatment of Neuroendocrine Cervical Carcinoma states that ovarian preservation may be carefully considered in selected Stage IA–IB patients with strong fertility or endocrine preservation preferences, provided that strict informed consent and rigorous perioperative assessment are ensured [1]. Nevertheless, evidence remains limited, and ovarian preservation in cervical LCNEC should be approached on an individualized, case-by-case basis.

The diagnostic challenges illustrated by this case underscore the need for heightened suspicion when colposcopic impressions and biopsy findings diverge during pregnancy. Although conservative guideline-based management of AIS and HSIL is appropriate in most cases [13, 14], negative punch biopsy results should not be interpreted as exclusionary when clinicopathologic discordance persists. In such high-risk settings, timely postpartum excisional evaluation is essential to avoid delayed recognition of occult invasive disease [7].

In summary, LCNEC during pregnancy may evade detection due to deep stromal invasion, surface masking by intraepithelial lesions, and dynamic physiological changes across gestation and postpartum involution. This case highlights that repeated negative biopsies do not reliably exclude invasive disease and reinforces the importance of integrating colposcopic assessment with an awareness of sampling limitations and a low threshold for definitive excision in discordant scenarios.

Abbreviations

AFP

Alpha-fetoprotein

AIS

Adenocarcinoma in situ

ASCCP

American Society for Colposcopy and Cervical Pathology

ASCUS

Atypical squamous cells of undetermined significance

CIN

Cervical intraepithelial neoplasia

DFS

Disease-free survival

EP

Etoposide and Platinum

FIGO

International Federation of Gynecology and Obstetrics

HPV

Human papillomavirus

HSIL

High-grade squamous intraepithelial lesion

LCNEC

Large cell neuroendocrine carcinoma

LEEP

Loop electrosurgical excision procedure

LESS

Laparoendoscopic single-site

MDT

Multidisciplinary team

NEC

Neuroendocrine carcinoma

NSE

Neuron-specific enolase

OS

Overall survival

PET-CT

Positron emission tomography-computed tomography

SCC

Squamous cell carcinoma

SCNEC

Small cell neuroendocrine carcinoma

SEER

Surveillance, Epidemiology, and End Results

SGO

Society of Gynecologic Oncology

TCT

Liquid-based cytology (ThinPrep cytologic test)

Biographies

LD

is a Senior Pathologist with expertise in gynecologic malignancies.

QL

is a Professor and Director of the Department of Obstetrics and Gynecology at Renji Hospital, School of Medicine, Shanghai Jiao Tong University.

DW

is the Chief Scientist specializing in gynecologic oncology at Ren Ji Hospital.

Authors’ contributions

DW and HY conceptualized the study and designed the research strategy. HY collected the clinical data and managed the patient’s treatment. LD performed the pathological examination and interpreted the immunohistochemical results. HY conducted the SEER database analysis and statistical calculations. HY and DW performed the systematic literature review. HY wrote the original draft of the manuscript. DW and QL critically revised the manuscript for important intellectual content. All authors have read and approved the final manuscript.

Funding

This work was supported by the Science and Technology Commission of Shanghai Municipality (Grant No. 23JC1403000), the Research Institute Construction Project of High-Level Local Universities in Shanghai (2023), and the Medical Key Strategic Project of Wuxi Health Commission.

Data availability

All data generated or analyzed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

Ethical review and approval were waived for this study by the Institutional Review Board (IRB) of Renji Hospital due to the retrospective nature of the research.

Consent for publication

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.

Competing interests

The authors declare no competing interests.