Neuroendocrine tumours of the cervix (NECC) constitute a rare but highly aggressive subtype of cervical carcinoma, accounting for only 2–4% of cases, and are the most common site for neuroendocrine carcinoma within the gynaecologic tract. These tumours are characterised by a poor prognosis, with survival often less than 2 years despite treatment. Diagnosis is primarily morphology-based and is supported by immunohistochemistry markers such as synaptophysin and chromogranin. NECC frequently presents with lymphovascular space invasion and high potential for lymphatic and haematologic spread, leading to a worse prognosis compared to stage-equivalent squamous or adenocarcinoma subtypes. Patients are often younger (median age 45) and commonly present with vaginal bleeding, pelvic pain, or systemic manifestations like weight loss and paraneoplastic syndromes due to the high likelihood of distant metastases. Common sites of metastasis include the lung, lymph nodes, liver, brain, and bone. High-risk Human Papillomavirus (HPV) infection, predominantly HPV18 and HPV16, is associated with 85% of small cell and large cell NECC cases, distinguishing cervical neuroendocrine carcinoma from those arising in other sites or from typical carcinoids. Given its rarity and aggressive nature, the optimal management of NECC remains challenging and largely undefined by prospective trials. Treatment guidelines are often extrapolated from retrospective studies, expert consensus, and protocols for small-cell lung cancer or other cervical cancer histologies. A multidisciplinary approach and multimodal therapy are recommended across all stages due to the high rates of recurrence. For early-stage disease, radical hysterectomy with lymph node assessment is the cornerstone of treatment. Neoadjuvant chemotherapy with platinum-based chemotherapy in combination with etoposide is recommended for tumours larger than 4 cm. Locally advanced disease is typically managed with concurrent chemoradiation using cisplatin and etoposide, followed by brachytherapy. Patients with distant metastases are offered palliative chemotherapy, with cisplatin-etoposide being the most commonly used regimen. Recent advances include the investigation of targeted therapies and immune checkpoint inhibitors (ICIs). While prospective data specific to NECC is limited, their established efficacy in other HPV-associated cervical cancers and small cell lung carcinoma, coupled with promising outcomes in case reports, make them attractive and emerging treatment options.

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Small Cell and Neuroendocrine Tumours of the Cervix

  • Cristina Mitric,
  • Dina Braik,
  • Amit Oza,
  • Al Covens

摘要

Neuroendocrine tumours of the cervix (NECC) constitute a rare but highly aggressive subtype of cervical carcinoma, accounting for only 2–4% of cases, and are the most common site for neuroendocrine carcinoma within the gynaecologic tract. These tumours are characterised by a poor prognosis, with survival often less than 2 years despite treatment. Diagnosis is primarily morphology-based and is supported by immunohistochemistry markers such as synaptophysin and chromogranin. NECC frequently presents with lymphovascular space invasion and high potential for lymphatic and haematologic spread, leading to a worse prognosis compared to stage-equivalent squamous or adenocarcinoma subtypes. Patients are often younger (median age 45) and commonly present with vaginal bleeding, pelvic pain, or systemic manifestations like weight loss and paraneoplastic syndromes due to the high likelihood of distant metastases. Common sites of metastasis include the lung, lymph nodes, liver, brain, and bone. High-risk Human Papillomavirus (HPV) infection, predominantly HPV18 and HPV16, is associated with 85% of small cell and large cell NECC cases, distinguishing cervical neuroendocrine carcinoma from those arising in other sites or from typical carcinoids. Given its rarity and aggressive nature, the optimal management of NECC remains challenging and largely undefined by prospective trials. Treatment guidelines are often extrapolated from retrospective studies, expert consensus, and protocols for small-cell lung cancer or other cervical cancer histologies. A multidisciplinary approach and multimodal therapy are recommended across all stages due to the high rates of recurrence. For early-stage disease, radical hysterectomy with lymph node assessment is the cornerstone of treatment. Neoadjuvant chemotherapy with platinum-based chemotherapy in combination with etoposide is recommended for tumours larger than 4 cm. Locally advanced disease is typically managed with concurrent chemoradiation using cisplatin and etoposide, followed by brachytherapy. Patients with distant metastases are offered palliative chemotherapy, with cisplatin-etoposide being the most commonly used regimen. Recent advances include the investigation of targeted therapies and immune checkpoint inhibitors (ICIs). While prospective data specific to NECC is limited, their established efficacy in other HPV-associated cervical cancers and small cell lung carcinoma, coupled with promising outcomes in case reports, make them attractive and emerging treatment options.