Major Genetic Syndromes
Cancer of the endometrium is the second most common cancer observed in LS families with initial estimates of cumulative risk in LS carriers of 30% to 39% by age 70 years.[215,217] In a large Finnish study of 293 putative LS gene carriers, the cumulative lifetime risk for endometrial cancer was 43%. Endometrial cancer risk was directly related to age, ranging from 3.7% at age 40 years to 42.6% by age 80 years, compared with a 3% endometrial cancer risk in the general population. The maximal risk for endometrial cancer in LS families occurs 15 years earlier than in the general population, with the highest risk occurring between ages 55 and 65 years. In a community study of unselected endometrial cancer patients in central Ohio, at least 1.8% (95% CI, 0.9%-3.5%) of newly diagnosed patients had LS. Adenocarcinomas of the lower uterine segment may carry a greater risk of manifesting LS.
In the general population, the diagnosis of endometrial cancer is generally made when women present with symptoms including abnormal or postmenopausal bleeding. An office endometrial sampling, or a dilatation and curettage (D&C), is then performed, providing a histologic specimen for diagnosis. Eighty percent of women with endometrial cancer present with stage I disease due to the presenting symptoms. There is no data suggesting the clinical presentation in women with LS differs from the general population.
Given their substantial increased risk for endometrial cancer, endometrial screening for women with LS has been suggested. Proposed modalities for screening include transvaginal ultrasound (TVUS) and/or endometrial biopsy. Although the Pap test occasionally leads to a diagnosis of endometrial cancer, the sensitivity is too low for it to be a useful screening test. The presence of endometrial cells in a Pap smear obtained from a postmenopausal woman not taking hormone replacement therapy is abnormal and warrants further investigation.[304,305] Two studies have examined the use of TVUS in endometrial screening for women with LS.[306,307] In one study of 292 women from LS or LS-like families, no cases of endometrial cancer were detected by TVUS. In addition, two interval cancers developed in symptomatic women. In a second study, 41 women with LS were enrolled in a TVUS screening program. Of 179 TVUS procedures performed, there were 17 abnormal scans. Three of the 17 women had complex atypical hyperplasia on endometrial sampling, while 14 had normal endometrial sampling. However, TVUS failed to identify one patient who presented 8 months after a normal TVUS with abnormal vaginal bleeding, and was found to have stage IB endometrial cancer. Both of these studies concluded that TVUS is neither sensitive or specific. A study of 175 women with LS, which included both endometrial sampling and TVUS, showed that endometrial sampling improved sensitivity over TVUS. Endometrial sampling found 11 of the 14 cases of endometrial cancer. Two of the three other cases were interval cancers that developed in symptomatic women and one case was an occult endometrial cancer found at the time of hysterectomy. Endometrial sampling also identified 14 additional cases of endometrial hyperplasia. Among the group of 14 women with endometrial cancer, ten also had TVUS screening with endometrial sampling. Four of the ten had abnormal TVUS, but six had normal TVUS. While this cohort study demonstrates that endometrial sampling may have benefits over TVUS for endometrial screening, there is no data that predicts screening with any other modality has benefits for endometrial cancer survival in women with LS. Given the favorable survival for endometrial cancer diagnosed by symptoms, it is unlikely that a sufficiently powered screening study will be able to demonstrate a survival advantage. Certainly, women with LS should be counseled that abnormal or postmenopausal vaginal bleeding warrants an endometrial sampling or D&C.