Regular articleEndocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma
Introduction
Endocrine tumors of the uterine cervix are rare; they typically exhibit aggressive behavior, and carry a poor prognosis [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. More than 15 diagnostic terms have been used to describe these tumors since the first case was described in 1972 (see Appendix) [12]. In 1997, four categories were proposed under the broad designation of endocrine tumors of the uterine cervix in order to clarify the diagnostic terminology [12].
Before much was known about endocrine tumors of the cervix, many of these tumors were classified as squamous cell carcinomas [1]. The unique morphologic, ultrastructural and immunohistochemical features of endocrine tumors have subsequently been described, promoting their recognition [1], [2], [3], [4], [11]. Recent studies characterizing the molecular abnormalities associated with endocrine tumors of the cervix have revealed that, like invasive squamous cell carcinoma of the cervix, human papillomavirus (HPV) subtypes 16 and 18 are detected in a high proportion of cases [13], [14], [15], [16], [17], [18], [19]. Molecular abnormalities such as deletions in chromosomal region 3p have been found in endocrine tumors, a change that is also seen in squamous cell carcinomas [15], [17]. Loss of the TP53 gene and allelic loss at chromosomal region 9p21 have been observed in a small number of endocrine tumors of the cervix as well, abnormalities that are commonly associated with neuroendocrine tumors of the lung but not squamous cell carcinomas in the cervix [17].
Studies that use population-based data and standardized diagnostic terminology can help to define the differences between endocrine and squamous cell tumors of the cervix. Population-based data sources provide relatively large numbers of cases and are not affected by selection bias due to institutional referral patterns. Many clinical case series have been published, but no population-based report on endocrine tumors of the cervix has been compiled to date. The objectives of this study were to provide the first population-based description of the incidence, demographic characteristics, and survival of endocrine tumors of the cervix and to highlight the unique features of these tumors by comparing them with the more common invasive squamous cell carcinoma of the cervix.
Section snippets
Methods
The Surveillance, Epidemiology and End-Results (SEER) program of the National Cancer Institute (Bethesda, MD) collects data from all persons diagnosed with cancer residing in specific geographically defined regions. Reporting to cancer registries in these jurisdictions is mandated by law, and representation of the U.S. population has increased from approximately 10% in 1993 to 14% in 2001 [20]. Quality control, with a standard case ascertainment set at 98%, is conducted annually in the SEER
Results
From 1973 to 1998, 259 endocrine tumors of the uterine cervix were reported to the SEER program. In 10 of these cases, there was no active follow-up, and another 10 were second or later primary malignancies. Thus, 239 cases (93%) were included in this analysis: 185 cases of small cell carcinoma, 51 cases of neuroendocrine carcinoma, and 3 carcinoid tumors. For invasive squamous cell carcinomas, 18,458 of 20,093 cases (92%) were eligible for inclusion in this study. There were 78 cases of
Discussion
Although rare, endocrine tumors of the uterine cervix are extremely aggressive and have a much worse prognosis than invasive squamous cell carcinomas. In our study, this behavior is reflected in the higher proportion of cases that present at FIGO stage IV, the high proportion of cases with lymph node involvement at diagnosis, and the poor survival of the women afflicted with endocrine tumors. Even after adjustment for age and stage at diagnosis, endocrine tumors had higher hazards of death than
Acknowledgements
The authors thank Ben F. Hankey, Sc.D., and Brenda K. Edwards, Ph.D., for advice and editorial support.
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