Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report

The present report describes a rare case of cervical adenocarcinoma with a coexisting neuroendocrine tumor (NET) G2 component that developed pulmonary metastases with proliferative escalation and possible transformation to neuroendocrine carcinoma (NEC). A 43-year-old woman with cervical adenocarcinoma (International Federation of Gynaecology and Obstetrics 2018 stage IB1) underwent radical hysterectomy, bilateral salpingectomy and pelvic lymph node dissection. The primary tumor had morphologic features of mixed adenocarcinoma and NET G2 [Ki-67, 3-30%; 5-8 mitoses/10 high-power fields (HPFs)], classified as postoperative pathological stage IB1 (pT1b1 N0 M0; American Joint Committee on Cancer 9th edition). After 2 years, chest computed tomography revealed multiple pulmonary nodules. Resection of a right middle lobe lesion revealed metastatic NET with increased proliferative activity (G3 based on gastrointestinal NET criteria; Ki-67 hotspot, 35%; >50 mitoses/10 HPFs). A left upper lobe lesion exhibited predominantly NET morphology, but focal areas exhibited high proliferative activity (Ki-67 hotspot, 93%; 50 mitoses per 10 HPFs) with features compatible with small cell carcinoma. The current case suggests a stepwise progression from NET toward NEC, highlighting the importance of monitoring proliferative indices in cervical NETs, re-evaluating metastatic lesions histologically and considering multimodal treatment strategies.