Updates and management algorithm for neuroendocrine tumors of the uterine cervix

Abstract

Neuroendocrine carcinomas of the cervix account for less than 2% of all invasive cervical cancers and are classified as low-grade (carcinoid, atypical carcinoid tumor) or high-grade (known as small- and large-cell) neuroendocrine carcinomas. There are increasing data showing that cervical neuroendocrine carcinomas may be associated with the human papillomavirus (HPV), especially HPV18, and most will stain positive for p16. Immunohistochemistry markers such as synaptophysin and CD56 are the most sensitive markers. Although there are no commonly associated mutations, PIK3CA, KRAS, and TP53 are the most frequently found mutations in neuroendocrine tumors. Neuroendocrine cervical carcinomas are exceedingly aggressive tumors with a high tendency for nodal involvement and distant metastases. Age, lymph node metastases, smoking, pure small-cell histology, and tumor size are independent prognostic factors. Overall, the 5-year survival rate is 36% and the median overall survival ranges between 22 and 25 months. Treatment options are often extrapolated from small-cell lung cancer and limited retrospective studies. The preferred treatment is a multimodal approach of surgery, chemoradiation, and systemic chemotherapy. The most common chemotherapy regimen used as initial therapy is a combination of cisplatin and etoposide. In the setting of recurrent disease, a combination of topotecan, paclitaxel, and bevacizumab has demonstrated favorable outcomes. Multicenter tumor registries, such as the Neuroendocrine Cervical Tumor Registry (NeCTuR), are an opportunity to evaluate patterns of disease treatment and oncologic outcomes.

Rare case of tonsillar and subcutaneous metastasis from neuroendocrine cervical cancer

“…Immunohistochemistry is important in the diagnosis of NECC. Synaptophysin, CD56, chromogranin A and neuron‐specific enolase are the most frequently used stains for neuroendocrine tumors . About 65% of NECC are positive for at least one of those markers .…”

“…Neuroendocrine cervical carcinoma (NECC) is a rare type of gynecologic malignancy, accounting for only 1–1.5% of all cervical cancers . Since 2014, NECC has been categorized by the World Health Organization as low‐grade and high‐grade neuroendocrine carcinoma . The former was previously referred to as carcinoid tumor and atypical carcinoid tumor and the latter as small‐cell and large‐cell neuroendocrine carcinoma.…”

“…NECC is characterized by its aggressive biological behavior with high incidence of lymphatic and distant metastasis. So far, there is no standard of care for NECC and multimodal therapies are utilized in its clinical management . As a result, prognosis of NECC remains poor, whose median overall survival is less than 2 years .…”

“…So far, there is no standard of care for NECC and multimodal therapies are utilized in its clinical management . As a result, prognosis of NECC remains poor, whose median overall survival is less than 2 years . And the 5‐year overall survival of NECC is about 35%, while that of all cervical cancers is over 65% …”

Neuroendocrine tumors of the cervix: an urgent call for joining forces

“…Gloria Salvo and co-authors have provided a review of this important topic in this month’s issue of the journal1 and add another piece to this complex mosaic. In this systematic review, the authors specifically addressed the etiology, histologic classification, and molecular profile of cervical neuroendocrine tumors.…”