Neuroendrocrine tumors of the uterine cervix: A therapeutic challenge for gynecologic oncologists

The most recent editions of the World Health Organization Classification of Gynecologic Tract tumors grouped cervical carcinoid tumor and atypical carcinoid tumor into low-grade NETs and cervical small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma into high-grade NETs. High-risk HPV DNA is detected in almost all cervical high-grade NETs. No treatment guidelines, based on prospective, well-designed clinical trials, are currently available due to the rarity of these tumors. Many authors have reported different multimodality approaches, mainly derived from NETs of the lung. These usually consist in radical hysterectomy followed by adjuvant chemotherapy or concurrent chemoradiation for early stage disease, definitive concurrent chemoradiation sometimes preceded by neoadjuvant chemotherapy and followed by adjuvant chemotherapy for locally advanced disease, and palliative chemotherapy for metastatic disease. In this systematic review, we address the histologic classification of cervical NETs, analyze their pathogenesis and overall prognosis, and evaluate the different treatment modalities described in the literature, in order to offer a possible algorithm that may help the clinicians in diagnosing and treating patients with these uncommon and aggressive malignancies.