Neuroendocrine Carcinomas in Gynecologic Oncology

Neuroendocrine carcinomas (NECs) of the female genital tract represent a rare and highly aggressive group of malignancies characterised by neuroendocrine morphology and the expression of peptide hormones or neuroamines. Although they account for less than 2% of gynaecologic neoplasms, their propensity for early lymphovascular invasion and distant metastasis confers a poorer prognosis than more common epithelial tumours. NECs may arise in the cervix, ovary, endometrium or vulva, with small-cell and large-cell subtypes reflecting distinct histopathological features and proliferation indices. Diagnosis relies on a combination of imaging, histological examination and immunohistochemical detection of markers such as synaptophysin and chromogranin A. In the absence of randomised trials, management strategies have been extrapolated from small-cell lung cancer and include radical surgery, platinum-based chemotherapy and radiotherapy in a multimodal approach. Recent advances in molecular profiling have begun to illuminate the genomic landscape of these tumours, revealing recurrent alterations in pathways such as PI3K/AKT/mTOR, RAS/MEK and aberrations associated with human papillomavirus infection in cervical cases. The identification of somatostatin receptors and other targetable markers has paved the way for novel therapeutic possibilities, including somatostatin analogues and immune checkpoint inhibitors. However, outcomes remain unsatisfactory, underscoring the urgent need for standardised diagnostic algorithms, robust prognostic biomarkers and tailored treatment regimens to improve survival and quality of life for affected women.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Neuroendocrine Carcinomas in Gynecologic Oncology publication trend

The graph below shows the total number of articles in neuroendocrine carcinomas in gynecologic oncology across all publications each year (not limited to Nature Index journals).

Technical terms

Neuroendocrine carcinoma (NEC): A malignant neoplasm exhibiting both neural and endocrine differentiation.

Small-cell and large-cell subtypes: Histological variants of NEC distinguished by cell size, nuclear features and mitotic activity.

Somatostatin receptors: Cell-surface proteins that bind somatostatin, often overexpressed in neuroendocrine tumours and targetable by analogues.

PI3K/AKT/mTOR pathway: A central intracellular signalling cascade regulating cell growth and survival, frequently altered in cancer.

Human papillomavirus (HPV): A DNA virus implicated in the pathogenesis of cervical neoplasms through integration and oncogene expression.

Immunohistochemistry (IHC): A laboratory technique using antibodies to detect specific antigens in tissue sections, aiding tumour classification.

Neoadjuvant and adjuvant therapy: Treatments administered before or after primary surgery, respectively, to improve outcomes.

Tumour mutational burden (TMB): The total number of somatic mutations per megabase of tumour DNA, used as a biomarker for immunotherapy response.

References

1. Advances in Research, Diagnosis, and Treatment of Neuroendocrine Cervical Carcinoma: A Review. Oncology Reviews (2023).
2. Genomic characterization of small cell carcinomas of the uterine cervix. Molecular Oncology (2021).
3. Unique Genomic Landscape of High-Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms. JCO Precision Oncology (2020).
4. Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5). Cancers (2020).