Clinicopathologic features and lymph node metastasis pattern of the cervical MiNEN

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare type of cervical tumor. Its clinicopathological features, lymph node (LN) metastatic patterns and outcomes are still unclear.We have analyzed the clinicopathological information of 26 patients with cervical MiNEN.The median age of onset for cervical MiNEN was 48 years. Macroscopically, polyps and nodules were the main types. The neuroendocrine components included small cell neuroendocrine carcinoma (SCNEC) (14/26 cases), large cell neuroendocrine carcinoma (LCNEC) (10/26 cases), and typical carcinoid (2/26 cases). Non-neuroendocrine components included adenocarcinoma (AC) (12/26, including one case of AC in situ) and squamous cell carcinoma (SC) (10/26) and adeno-squamous cell carcinoma (ASC) (4/26). Of the 16 AC cases, 15 were human papilloma virus (HPV)-associated AC and one was HPV-independent AC. Except for the case of MiNEN with HPV-independent AC, all cases were diffusely and strongly positive for p16 protein. The lympho-vascular space invasion (LVSI) was seen in 17/26 cases, and the components that invade lymphatic vessels were mainly neuroendocrine carcinomas (NECs) (15/17), followed by SC (1/17) and AC (1/17). Ten patients developed LN metastases, including six in combined SCNECs (6/14) and four in combined LCNECs (4/10); the metastatic component was pure NEC in eight cases (8/10) and SC or AC in two cases (2/10).NEC component is the key factor that determines the clinical behavior and prognosis of cervical MiNEN.