Cervical small-cell neuroendocrine carcinoma mixed with squamous cell carcinoma first suspected on liquid-based cytology and confirmed by biopsy: a case report

Cervical small cell neuroendocrine carcinoma (SCNEC) admixed with squamous cell carcinoma (SCC) is a rare malignancy associated with a poor prognosis. While histological features of this mixed tumor have been described, liquid-based cytology (LBC) findings remain largely undocumented, despite prior multi-center studies describing pure SCNEC. Herein, we report a case of mixed cervical SCNEC-SCC in a 69-year-old woman. The lesion was initially suspected via LBC screening and subsequently confirmed using limited cervical biopsy specimens, no surgical resection specimen was available. Cytologically, the SCNEC component presented as small round cells in loose clusters or isolated single cells, exhibiting a high nuclear-to-cytoplasmic ratio. These cells typically featured delicate yet irregular nuclear membranes, hyperchromatic nuclei, inconspicuous nucleoli, scant cytoplasm, frequent crush artifacts, scattered mitoses, and focal tumor necrosis. In contrast, other cells displayed slightly more abundant cytoplasm with visible nucleoli, representing the SCC component. We quantitatively describe component proportions using a multi‑pathologist consensus‑based cell‑counting approach and elaborate on characteristic cytologic features, including tumor necrosis, mitotic activity, and crush artifacts, to facilitate differential diagnosis. Owing to sampling limitations intrinsic to small size biopsy specimens, histologically derived tumor component percentages should be interpreted prudently, as they may not reflect the true composition of the entire lesion. Careful evaluation of atypical malignant cells on LBC is essential to avoid misdiagnosis of this aggressive neoplasm. Importantly, although LBC can identify dual-lineage malignant cells during screening, this single case study cannot establish causal or correlative links between cytological detection and overall survival. Early cytological recognition failed to improve clinical outcomes in this patient, who presented with widespread radiologically suspected metastatic disease at initial diagnosis; therefore, no generalized survival conclusions can be drawn from this single case.