Case Report: Neuroendocrine-marker–negative high-grade neuroendocrine carcinoma mimicking squamous cell carcinoma: an underrecognized diagnostic pitfall
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By
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Wen He
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Ying Tang
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Yan Li
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Jianfeng Zhang
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Xuyang You
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Qiaozhen Wu
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May 8, 2026
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Clinical Scorecard: Case Study: High-Grade Neuroendocrine Carcinoma Lacking Neuroendocrine Markers Resembling Squamous Cell Carcinoma – A Diagnostic Challenge
At a Glance
| Category | Detail |
|---|
| Condition | |
| Key Mechanisms | Lack of traditional neuroendocrine markers; POU2F3, YAP1, and ASCL1 transcription factors; squamoid morphology. |
| Target Population | |
| Care Setting | |
Key Highlights
- High-grade NEC can mimic squamous cell carcinoma due to absence of neuroendocrine markers.
- Molecular profiling (90-GEP) is crucial for accurate diagnosis in NE-marker-negative cases.
- Platinum-based chemotherapy (etoposide and carboplatin) is effective for high-grade NEC.
- Molecular profiling can reveal hidden neuroendocrine differentiation.
Guideline-Based Recommendations
Diagnosis
- Utilize enhanced immunohistochemistry and molecular lineage assays for accurate classification, including POU2F3 and YAP1.
Management
- Administer platinum-based chemotherapy for high-grade NEC.
Monitoring & Follow-up
- Monitor clinical progression and NSE levels for treatment response.
Risks
- Misdiagnosis as NSCLC may lead to ineffective treatment and delayed appropriate therapy.
Patient & Prescribing Data
Elderly male with significant smoking history and advanced high-grade NEC.
Significant clinical response observed with etoposide and carboplatin therapy.
Clinical Best Practices
- Integrate molecular assessments when traditional markers are absent.
- Consider tumor heterogeneity and sampling bias in needle biopsies.
- Utilize gene expression profiling (GEP) to clarify lineage uncertainty.
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