Clear Cell Adenocarcinoma Of Vagina Research Articles

Late Cervical And Vaginal Clear Cell Adenocarcinoma In Women Exposed In Utero To Diethylstilbestrol: Evaluation And Screening.

We aimed to evaluate the risk of cervical and vaginal clear cell adenocarcinoma (CCA) in women, aged 50 years or more, exposed in utero to diethylstilbestrol (DES) and contribute to a reevaluation of the recommendations for cervical and vaginal cancer and pre-cancer screening for these women. We carried out a retrospective review for patients received in a cancer institute. Two cohorts were consecutively studied, the first from 1970 to 2003 and the second from 2004 to 2021, and then linked. During the first period, we observed 61 CCA cases, with a mean age at diagnosis of 23 years (7-42), 36 (59%) following DES exposure in utero. During the second period, we found 27 cases, with one case of DES exposure (4%) for a women diagnosed at the age of 40 years. The mean age of the second cohort was 38 years (14-79). For the seven women aged 50 years or more at the time of CCA diagnosis, DES exposure was excluded for five and considered unlikely for the other two. In total, 88 cases of cervical or vaginal CCA were observed over a period of 51 years in a cancer center. The 37 cases associated with DES exposure represented approximatively one third of the CCA related to DES expected in France. DES exposure was improbable for the seven cases of CCA for women aged 50 years or more. These results do not support the hypothesis of late cervical or vaginal CCA in women exposed to DES in utero and indicate the need for larger multicentric studies. For the present, we propose specific screening for women exposed to DES in utero in terms of : 1) methods: association of cytology and hrHPV testing, with cervical and vaginal sampling, 2) timing : annual, or without exceeding a three-year interval, continuing after 65 years of age and after hysterectomy.

Primary Vaginal Clear Cell Adenocarcinoma: Case Report with Literature Review

Primary Vaginal Clear Cell Adenocarcinoma: Case Report with Literature Review

Primary clear cell adenocarcinoma of the vagina in a young female with uterus didelphys

Adenocarcinomas of clear cell type are uncommon tumors accounting for 5-10% of all vaginal tumours which in turn account for approximately 2% of all gynaecologic malignancies. Though Clear cell Adenocarcinomas arising in the setting of previous Di-Ethyl–Stilbesterol [DES] exposure have been reported quite often, only few cases of these not associated with DES have been documented. Amongst non-DES exposed patients, CCAs are said to be sporadic or in association with endometriosis in women of peri/postmenopausal age or in association with some congenital genitourinary anomalies mostly affecting young females. A 16 year old female presented with heavy bleeding per vaginum since 2 months. On per vaginal examination a polypoidal mass was felt on posterior wall of vagina. Ultrasonography revealed the presence of a uterus didelphys in addition to this mass. Polypectomy was done. On microscopy, a diagnosis of clear cell adenocarcinoma was made which was confirmed on immunohistochemistry. There was no history of any DES exposure in the mother. We present here a case of an adolescent female with uterus didelphys and no DES exposure who was diagnosed as a case of Vaginal Clear cell Adenocarcinoma. The rarity of this tumour among DES-exposed cases and its presence in non-exposed patients warrants a more thorough search for the underlying pathology.

Abstract 709: Incidence and mortality of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: 40 years of long-term follow-up

Abstract Objective: Women exposed to diethylstilbestrol (DES) in utero are at increased risk for the development of vaginal and cervical clear cell adenocarcinoma (CCA), and possibly of breast cancer, diabetes, and cardiovascular diseases as well. A peak in the age-incidence curve in DES- related CCA has been documented at ages 19 to 24. It is unknown if a second peak will occur in later life, the ages when CCA developed spontaneously in the pre-DES era. In addition, the long-term prognosis and health impact for adolescents and young adults who have DES-related CCA are unknown. Methods: 720 cases of CCA were reviewed from the CCA Registry at the University of Chicago through 2014. Rates and cumulative risks for CCA were calculated based on white women born in the U.S. from 1948 through 1971. Kaplan-Meier method was used to estimate survival probability among women with CCA. Cox models were used to identify independent prognostic factors. To gauge the relative impact of young-onset clear-cell adenocarcinoma on mortality, we compared their mortality hazards with mortality hazards of the U.S. female population, and calculated standardized mortality ratio (SMR). Results: In 420 CCA cases there was documented evidence of prenatal DES exposure. 80% patients had a CCA between ages 15 and 31 but some occurred as late as age 55. A small second peak occurred around age 40. The risk of U.S. born, white DES-related CCA was highest in the 1951-1956 birth cohort, and this birth cohort effect correlated with DES use in the U.S. By age 50, the cumulative risk of CCA was 1 per 750 exposed women. A total of 695 CCA patients were included in the survival analysis. After a median follow-up of 22.7 years (interquartile range: 10.8-35.1 years), 219 patients died. The 5-year, 10-year, and 20-year survival probabilities were 83%, 75%, and 69%, respectively. As expected, tumor stage was a strong prognostic factor for survival among DES-related CCA cases. Tubular-cystic histology was associated with better survival compared with papillary, solid, or a combination of these histological patterns. Adolescent patients (<18 years old) had worse survival than young adult patients. Compared with general U.S. female population, women with DES-related CCA had 27-fold increased risk of death between 10 and 35 year of age (SMR 27.06, 95% CI: 23.04-31.58), 5-fold increased risk between 35 and 50 year of age (SMR 5.07, 95% CI: 3.59-6.95), 2-fold increased risk after age 50 (SMR 2.03, 95% CI: 1.22-3.18). Conclusion: Our study drew a relatively complete epidemic curve of DES-related CCA. There existed late-onset CCA among women with prenatal exposure of DES. DES-related CCA increased mortality not only during early life among exposed women, but also impacted life after age 50. These results suggest continued close health follow-up of this population. Citation Format: Dezheng Huo, Diane Anderson, Arthur L. Herbst. Incidence and mortality of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: 40 years of long-term follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 709. doi:10.1158/1538-7445.AM2017-709

Diethylstilbestrol: Potential health risks for women exposed in utero and their offspring.

Diethylstilbestrol (DES) is a synthetic estrogen given to pregnant women to prevent miscarriages and preterm labor; the drug was used between 1941 and 1971 in the United States and into the 1980s in other countries. DES exposure is associated with significant long-term health effects, including increased risk for breast cancer, cervical and vaginal clear cell adenocarcinoma, reproductive tract abnormalities, infertility, poor pregnancy outcomes, and early menopause. This article reviews the potential health risks associated with DES exposure, how to assess which patients are at risk, and management recommendations for patients exposed to DES.

Adénose vaginale : à propos d’une observation et revue de la littérature

We report a case of vaginal adenosis in a woman of 42years. This is a rare congenital disorder since cessation of use of diethylstilbestrol (DES), usually of benign course, not to ignore in its tubo-endometrial histological form which may progress to atypical adenosis precursor of vaginal clear cell adenocarcinoma in patients exposed in utero to DES.

Diethylstilbestrol 暴露歴のない腟原発明細胞腺癌の 1 例

Diethylstilbestrol 暴露歴のない腟原発明細胞腺癌の 1 例

Non-diethylstilbestrol exposed vaginal clear cell adenocarcinoma has a common molecular profile with ovarian clear cell adenocarcinoma: A case report

•Primary vaginal clear cell adenocarcinoma (PVCCA) coexists with urinary tract anomalies without exposure to diethylstilbestrol in some cases.•PVCCA in our case showed genetic alterations of well-known cancer related genes, including a mutation of PIK3CA.•The genetic profile suggests that the carcinogenesis of PVCCA might have elements common with that of OCCA.

Clear cell adenocarcinoma of vagina associated with uterine prolapse: A rare entity

Introduction: Clear cell adenocarcinoma usually affects the cells of the female genital tract. In this cancer, cells become vacuolated and filled with glycogen hence it is called clear cell. This cancer is insidious and slow growing. Here we report a case of uterine prolapse with polypoidal growth in the vagina which on histopathological examination was diagnosed as a case of clear cell adenocarcinoma of the vagina. Case Report: A 27­year­old women with three previous vaginal deliveries presented with complaint of something coming out pervaginum, associated with bleeding and discharge pervaginum for the last one year. She was diagnosed as a case of uterine prolapse with vaginal clear cell adenocarcinoma. Conclusion: Based on the cases mentioned previously and one reported here vaginal clear cell adenocarcinoma is a rare entity and can also exist even without diethylstilbestrol (DES) exposure in utero.

A case of vaginal clear cell adenocarcinoma with congenital malformation of the urogenital tract

A case of vaginal clear cell adenocarcinoma with congenital malformation of the urogenital tract

Clear Cell Adenocarcinoma of the Female Genital Tract: Long-Term Outcome and Fertility Aspects After Brachytherapy Aimed at a Conservative Treatment

To assess the outcome and the fertility aspects in the particular population of cervical and/or vaginal clear cell adenocarcinoma (CCA) associated or not to previous in utero diethylstilbestrol exposure. From January 1970 to December 2003, data from 61 consecutive patients with cervical and/or vaginal histologically proven CCA treated with brachytherapy (BT) aimed at a conservative treatment at the Institut Gustave Roussy as a part of treatment were retrospectively analyzed. The median follow-up was 9.4 years, ranging from 0.3 to 27.4 years. The 5-year specific overall survival rate was 79%. The median time of disease-free survival was 5.8 years. In the subgroup of 42 patients with a cervical CCA, 12 patients tried to be pregnant, 2 patients became pregnant and had miscarriages (P2M2 and P1M1). No pregnancy has been observed in 10 patients exclusively owing to anomalies of the reproductive tract: 6 patients had partial or total diaphragm, 2 patients had an anatomical alteration of the uterus, 1 patient had atrophic endometrium, and 1 patient had primary infertility. In the subgroup of 19 patients with a vaginal CCA, 7 patients tried to be pregnant. All of them had no morphological and/or functional anomalies of the genital tract. Three of 7 patients had delivered healthy babies (P1D1, P2D2, and P3M2D1), and another one had a miscarriage (P1M1). Moreover, all babies were delivered by cesarean section. The pregnancy rate was 10% (6 of 61 patients) with 3 healthy babies. Conservative approach in patients with female genital tract CCA including BT gives good results with good survival rates and an interesting global pregnancy rate.

The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero

Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well documented case in human history. DES, an orally active synthetic estrogen, was believed to prevent adverse pregnancy outcome and thus was routinely given to selected pregnant women from the 1940s to the 1960s. It has been estimated that 5 million pregnant women worldwide were prescribed DES during this period. In the early 1970s, vaginal clear cell adenocarcinomas (CCACs) were diagnosed in daughters whose mother took DES during pregnancy (known as DES daughters). Follow-up studies demonstrated that exposure to DES in utero causes a spectrum of congenital anomalies in female reproductive tracts and CCACs. Among those, cervical and vaginal adenoses are most commonly found, which are believed to be the precursors of CCACs. Transformation related protein 63 (TRP63/p63) marks the cell fate decision of Müllerian duct epithelium (MDE) to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression in mice and induces adenosis lesions in the cervix and vagina. This review describes mouse models that can be used to study the development of DES-induced anomalies, focusing on cervical and vaginal adenoses, and discusses their molecular pathogenesis.

Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice

Proliferation and differentiation of cells in female reproductive organs, the oviduct, uterus and vagina, are regulated by endogenous estrogen. In utero exposure to a synthetic estrogen, diethylstilbestrol (DES), induces vaginal clear-cell adenocarcinoma in humans. In mice, perinatal exposure to DES results in abnormalities such as polyovular follicles, uterine circular muscle disorganization and persistent vaginal epithelial cell proliferation. We reported the persistent gene expression change such as interleukin-1 (IL-1) related genes, insulin-like growth factor-I (IGF-I) and its downstream signaling in the mouse vagina exposed neonatally to DES. In this study, we found persistent up-regulation of Wnt4 and persistent down-regulation of Wnt11 in the vagina of mice exposed neonatally to DES and estrogen receptor α specific ligand. Also Wnt4 expression in vagina is correlated to the stratification of epithelial cells with the superficial keratinization of vagina, but not epithelial cell stratification only.

Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol

Diethylstilbestrol (DES) was commonly given to pregnant women in the United States in the 1940s to prevent complications of pregnancy. Its use declined after publication of several studies in the early 1950s, which found no evidence of efficacy. DES was no longer prescribed in pregnant women after 1971 following publication of a study reporting a strong association between in utero exposure to DES and the occurrence of clear cell adenocarcinoma of the vagina and cervix in adolescent girls and young women. Several subsequent studies showed that exposure in utero was also associated with developmental defects of the genital tract and other adverse outcomes. Although DES has not been used in pregnant women for 4 decades, there is continuing concern for cumulative adverse outcomes among the millions of women with a history of in utero exposure. These cumulative effects are poorly understood. This follow-up study investigated the long-term outcomes among 4653 women exposed in utero to DES who had participated in 3 cohort studies initiated in the mid-1970s. The control group was comprised of 1927 unexposed women. The cumulative risks of 12 adverse outcomes significantly associated with DES exposure in previous analyses of the cohort were examined, including cumulative risks among women to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes. The relationships of these outcomes to vaginal epithelial changes (a histological marker of high-dose and early exposure to DES in utero) also was investigated. The cumulative risks for individual adverse outcomes in women exposed to DES compared with unexposed controls were as follows: (1) infertility: 33.3% versus 15.5% (hazards ratio [HR], 2.37; 95% confidence interval [CI], 2.05–2.75); (2) spontaneous abortion at <37 weeks' gestation: 50.3% versus 38.6% (HR, 1.64; 95% CI, 1.42–1.88); (3) preterm delivery at <37 weeks' gestation: 53.3% versus 17.8% (HR, 4.68; 95% CI, 3.74–5.86); (4) loss of pregnancy in second trimester at 14 to 27 weeks' gestation: 16.4% versus 1.7% (HR, 3.77; 95% CI, 2.56–5.54); (5) ectopic pregnancy: 14.6% versus 2.9% (HR, 3.72; 95% CI, 2.58– 5.38); (6) preeclampsia: 26.4% versus 13.7% (HR, 1.42; 95% CI, 1.07–1.89); (7) stillbirth at >27 weeks' gestation: 8.9% versus 2.6% (HR, 2.45; 95% CI, 1.33–4.54); (8) early menopause: 5.1% versus 1.7% (HR, 2.35; 95% CI, 1.67–3.31); (9) grade 2 or higher cervical intraepithelial neoplasia: 6.9% versus 3.4% (HR, 2.28; 95% CI, 1.59–3.27); and (10) breast cancer at 40 years of age or older: 3.9% versus 2.2% (HR, 1.82; 95% CI, 1.04–3.18). Data for 2 other outcomes, neonatal death and clear cell adenocarcinoma, were unreliable due to the small number of cases. The risks for most outcomes were higher among exposed women with vaginal epithelial changes compared with those without such changes. These findings show a high lifetime risk of several adverse health outcomes among women exposed in utero to DES.

A case of vaginal clear cell adenocarcinoma complicated with congenital anomalies of the genitourinary tract and metanephric remnant without prenatal diethylstilbestrol exposure

Vaginal clear cell adenocarcinoma (CCA) is well known to be associated with prenatal diethylstilbestrol exposure. We present a vaginal CCA with congenital anomalies of the genitourinary tract without prenatal diethylstilbestrol exposure. A 54-year-old woman complained of a 3-month history of genital bleeding. The examination revealed CCA at the anterior vagina and congenital anomalies. An anterior pelvic exenteration was performed. Macroscopically, bicornuate uterus, vaginal septum and left ureteral agenesis were found. Microscopically, vaginal CCA coexisted with adenosis and both metanephric and mesonephric remnants. The vaginal CCA was supposed to derive from coexisting adenosis. The adenosis was also supposed to occur as a congenital basis, together with genitourinary tract anomalies. Relations between congenital anomalies of the genitourinary tract and vaginal adenocarcinoma were suspected, resultantly.

Vaginal and (Uncommon) Cervical Cancers in the Netherlands, 1989-2003

The clinical and prognostic evaluation of cervical and vaginal tumors other than squamous cell and adenocarcinomas is hampered by the low incidence, and clinical and epidemiological studies on these uncommon tumors are scarce. Having close affinity with the pathology laboratories, the Netherlands Cancer Registry offers a great opportunity to study frequency, stage, treatment, and survival of uncommon tumors in the cervix and vagina and separately, the clear cell adenocarcinoma of the vagina and cervix. All invasive cervical tumors (n = 10,570) and all in situ and invasive vaginal tumors (n = 778) diagnosed in the Netherlands during 1989-2003 were selected from the Netherlands Cancer Registry. Age, stage at diagnosis, and treatment were described for each histological subgroup to find differences between common and uncommon tumors, including 5-year relative survival rates. Twenty-five patients (3%) with cervical cancer subsequently developed a vaginal tumor (during 1989-2003), and 19 of these patients underwent hysterectomy for their cervical cancer. A significantly worse prognosis was found for patients with small cell neuroendocrine cervical tumors and for patients with vaginal melanomas. Patients with clear cell adenocarcinoma of the vagina and cervix were found across all age categories. The less common histological types of cervical and vaginal cancers were clearly different from squamous cell carcinomas, especially with respect to age at diagnosis and survival rates. Spreading population-based knowledge of effects of treatment of these uncommon tumors should help clinical decision making and therefore improve prognosis.

Cancer risk in DES daughters.

ObjectiveWe examined long-term risk of cancer in women exposed to diethylstilbestrol (DES) in utero.MethodsA total of 12,091 DES-exposed women in the Netherlands were followed prospectively from December 1992 till June 2008. Cancer incidence was assessed through linkage with the Dutch pathology database (PALGA) and the Netherlands Cancer Registry and compared with the Dutch female population.ResultsA total of 348 medically verified cancers occurred; median age at end of follow-up was 44.0 years. No overall increased risk of cancer was found (standardized incidence ratio [SIR] = 1.01; 95% confidence interval [CI] = 0.91, 1.13). The risk of clear cell adenocarcinoma of the vagina and cervix (CCA) was statistically significantly increased (SIR = 24.23; 95% CI = 8.89, 52.74); the elevated risk persisted above 40 years of age. The risk of melanoma diagnosed before age 40 was increased (SIR = 1.59; 95% CI = 1.08, 2.26). No excess risks were found for other sites, including breast cancer.ConclusionsExcept for an elevated risk of CCA, persisting at older ages, and an increased risk of melanoma at young ages, we found no increased risk of cancer. Longer follow-up is warranted to examine cancer risk at ages when cancer occurs more frequently.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-010-9526-5) contains supplementary material, which is available to authorized users.

Neonatal Exposure to Diethylstilbestrol Alters Expression of DNA Methyltransferases and Methylation of Genomic DNA in the Mouse Uterus

Perinatal exposure to diethylstilbestrol (DES) can have numerous adverse effects on the reproductive organs later in life, such as vaginal clear-cell adenocarcinoma. Epigenetic processes including DNA methylation may be involved in the mechanisms. We subcutaneously injected DES to neonatal C57BL/6 mice. At days 5, 14, and 30, expressions of DNA methyltransferases (Dnmts) Dnmt1, Dnmt3a, and Dnmt3b, and transcription factors Sp1 and Sp3 were examined. We also performed restriction landmark genomic scanning (RLGS) to detect aberrant DNA methylation. Real-time RT-PCR revealed that expressions of Dnmt1, Dnmt3b, and Sp3 were decreased at day 5 in DES-treated mice, and that those of Dnmt1, Dnmt3a, and Sp1 were also decreased at day 14. RLGS analysis revealed that 5 genomic loci were demethylated, and 5 other loci were methylated by DES treatment. Two loci were cloned, and differential DNA methylation was quantified. Our results indicated that DES altered the expression levels of Dnmts and DNA methylation.

VAGINAL CLEAR CELL ADENOCARCINOMA WITH EARLY PULMONARY METASTASIS IN A CHILD

Although a few cases of vaginal clear cell adenocarcinoma (CCAC) have been reported in the ages under 14, they have presented in a much more aggressive form than the CCAC cases in higher ages and parenchymal pulmonary metastasis are known to occur following the primary tumor. This is a case report of a primary vaginal CCAC in an 8.6-year-old girl with no history of DES exposure who presented with vaginal bleeding and abdominal pain and the imaging signs of pulmonary metastasis at the presentation. Diagnostic imaging modalities should be considered for any child complaining of vaginal bleeding, due to limitation of vaginal examination. Chest X-ray is recommended at the time of diagnosis of CCAC and at follow-up sessions for early diagnosis of pulmonary metastasis.

Fertility-sparing radical abdominal trachelectomy for clear cell adenocarcinoma of the upper vagina: A case report

Background. Clear cell adenocarcinoma (CCA) of the vagina is traditionally treated with radical surgical resection with tailored postoperative radiation when indicated. Due to a bimodal distribution, women of reproductive age are frequently affected and could benefit from radical trachelectomy to preserve fertility. Case. A 22 year old female was diagnosed with clinical stage I vaginal clear cell adenocarcinoma in the left fornix abutting the cervix. The patient desired future fertility; therefore, she underwent radical abdominal trachelectomy and upper vaginectomy. Twenty-eight months after initial surgery, she has no evidence of recurrence with regular menstrual cycles. Conclusion. For patients with CCA of the upper vagina, where removal of the cervix is necessary, a radical trachelectomy with upper vaginectomy should be considered to conserve fertility.