Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy
Introduction
Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) was first described in 1957 [1]. It is a rare finding, representing 2%–5% of all cervical malignancies [2], [3], [4], [5]. The natural history of this disease differs from the more commonly seen squamous cell or adenocarcinoma of the cervix [6]. Patients diagnosed with SCNEC are more likely to have lymph node metastases and lymph vascular space invasion, and their clinical course is frequently marked by local and distant failure [5], [7], [8]. Five-year survival rates vary from 0% to 30% [9], [10]. Long-term survival can be achieved only in patients with limited stage disease [9], [11], [12].
Like small cell lung cancer, outcome of SCNEC is significantly associated with the extent of disease. Limited stage disease, which is defined as disease that can be encompassed within a radiation field, is treated with curative intent with combined modality therapy, with approximately 30% of patients achieving a cure. Patients with extensive stage disease – defined as disease outside of these confines – have a dismal prognosis with few surviving beyond two years [9], [13].
Due to the rarity of this disease, it has been difficult to conduct prospective trials. Based on retrospective studies and treatment paradigms established for small cell lung carcinoma, many clinicians favor the use of combined modality therapy (surgery followed by combined chemoradiation therapy) for limited stage disease, definitive chemo-radiation therapy for locoregional advanced disease, and palliative chemotherapy for metastatic disease. It is not known if these treatment modalities ultimately improve survival. Clear treatment recommendations for SCNEC have not been defined.
We performed a retrospective review to explore the outcomes and pattern of recurrence in patients with SCNEC and to determine the effects of chemotherapy on the recurrence-free and overall survival in patients with early stage disease.
Section snippets
Methods
After obtaining Institutional Review Board approval, we used the prospectively-maintained Virginia K. Pierce database to identify all patients with the diagnosis of SCNEC from January 1990 to February 2007.
All available pathology slides and reports were obtained and examined by two gynecologic pathologists (KJP and HZ). Histologically, SCNEC is similar to small cell carcinoma of other sites. Characteristic findings on hematoxylin–eosin staining include a diffusely infiltrating tumor composed of
Results
Between January 1990 and February 2007, 22 patients were identified. Five of the 22 cases were excluded. In 2 cases slides were not available for evaluation and in 3 cases findings did not meet the histologic criteria for SCNEC. Of the 17 patients who were diagnosed SCNEC, 13 (77%) had positive staining for one or more neuroendocrine markers.
Clinical characteristics are listed in Table 1. All 8 patients selected to undergo primary surgery underwent a lymph node dissection (Table 2). Three of 8
Discussion
SCNEC is rare and the prognosis is limited due to the tumor's propensity for distant hematogenous metastases. Given the rarity of SCNEC, prospective studies are missing or had to be discontinued preterm because of inadequate accrual [13]. Retrospective reports have shown that the natural history of this disease differs from the more commonly seen squamous cell or adenocarcinoma of the cervix in that patients diagnosed with small cell carcinoma of the cervix are more likely to have lymph node
Conflict of interest statement
The authors have no conflicts of interest to declare.
References (19)
- et al.
Small cell carcinoma of the cervix: a clinical and flow-cytometric study
Gynecol. Oncol.
(1991) - et al.
Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma
Gynecol. Oncol.
(2003) - et al.
Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence
Gynecol. Oncol.
(2004) - et al.
Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine carcinoma of the uterine cervix
Gynecol. Oncol.
(2001) - et al.
Should aggressive surgery ever be part of the management of small cell lung cancer?
Thorac. Surg. Clin.
(2004) - et al.
Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with completed resected stage I–IIIa small cell lung cancer: the Japan Clinical Oncology Lung Cancer Study Group Trial (JCOG9101)
J. Thorac. Cardiovasc. Surg.
(2005) - et al.
Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: its time has come
J. Thorac. Cardiovasc. Surg.
(2005) - et al.
Analytical study of the cells in cervical squamous-cell cancer
Lab. Invest.
(1957) - et al.
Carcinoid of the uterine cervix: additional observations on a new tumor entity
Cancer
(1976)