Adenocarcinoma of the vagina in adolescence.A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas)

Herbst, Arthur L.; Scully, Robert E.

doi:10.1002/1097-0142(197004)25:4<745::aid-cncr2820250402>3.0.co;2-2

Cited by 407 publications

(81 citation statements)

References 21 publications

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“…2 ) Despite lack of evidence supporting a benefit, DES continued to be prescribed during pregnancy until 1971, when a small study showed a stunning 40-fold increase in the risk of clear cell adenocarcinoma (CCA) of the vagina and cervix in girls and young women who were prenatally exposed to DES. 3 Several months later, the Food and Drug Administration issued a bulletin indicating that the use of DES was contraindicated in pregnancy. By then, however, millions of women, along with their sons and daughters, had been needlessly exposed.…”

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confidence: 99%

The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy

2016

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NIHAlthough the basic tenet of medicine is "First, do no harm, " history is filled with good intentions that were at best unhelpful and at worst harmful. Because medicine seeks to cure afflictions, there is an overwhelming desire on the part of health providers and patients to administer treatment. In certain settings, treatment can be reasonable despite a risk of adverse consequences: for example, if the disease is cured or its morbidity abated and the treatment consequences are less disabling than the disease itself.In the absence of overt disease, the question of whether to apply an intervention is far more challenging. The safety of interventions must be weighed against the population's level of risk, the morbidity and/or mortality associated with the disease, and the intervention's efficacy (eg, BRCA1 mutation, mastectomy, reduced breast cancer risk). Interventions must meet an especially high standard of safety and efficacy when administered in low-risk populations or in settings in which the morbidity associated with the disease is minor. In the worst-case scenario, an intervention may be both ineffective for its primary purpose and cause iatrogenic illness.Interventions in pregnancy are especially problematic because of the complex physiology of the condition and the possibility of causing short-and long-term adverse consequences in both the mother and her offspring. The continuing story of diethylstilbestrol (DES), a synthetic estrogen, shows the importance of caution when evaluating the merits of interventions involving pregnant women. With regard to DES, investigators believed that pregnancy loss was caused in part by a decrease in estrogen and that administering DES to pregnant women would help maintain a healthy pregnancy. Moreover, because endogenous estrogen concentrations increase dramatically during a healthy pregnancy, supplementation with DES was deemed harmless. During its early years of use, DES was administered to women with threatened pregnancy loss or a history of pregnancy loss. Eventually, DES was advertised to the medical community for "routine by guest on May 10, 2018 http://pediatrics.aappublications.org/ Downloaded from PEDIATRICS Volume 138 , number s1 , November 2016 S43 prophylaxis in ALL pregnancies" and administered to women with otherwise healthy pregnancies ( Fig 1).By the time DES was formally evaluated, it was standard of care in high-risk obstetrics practices. The first clinical trial to determine the efficacy of DES, reported in 1953, 1 showed that DES did not improve pregnancy outcome. (Indeed, a subsequent reanalysis of the data revealed that DES increased the risk of spontaneous abortion, preterm birth, and neonatal death. 2 ) Despite lack of evidence supporting a benefit, DES continued to be prescribed during pregnancy until 1971, when a small study showed a stunning 40-fold increase in the risk of clear cell adenocarcinoma (CCA) of the vagina and cervix in girls and young women who were prenatally exposed to DES. 3 Several months later, the Food and Drug Administrati...

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The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy

2016

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“…An additional problem is that the hormone assays in the Boston Study were later found to be faulty and not to actually measure progesterone (Louis L. Engel, PhD, personal communication). It is believed that DES continued to be heavily used in the 1960s, and it has been estimated that 2 to 4 million women in the United States took DES during pregnancy [6].Then, in the late 1960s, eight extraordinarily rare cases of clear cell adenocarcinoma (CCA) of the vagina were diagnosed and treated in women in their teens and early 20s in the Boston area [7]. No such cluster of cases in young patients had ever been seen previously.…”

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“…Then, in the late 1960s, eight extraordinarily rare cases of clear cell adenocarcinoma (CCA) of the vagina were diagnosed and treated in women in their teens and early 20s in the Boston area [7]. No such cluster of cases in young patients had ever been seen previously.…”

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Diethylstilbestrol (DES) Pregnancy Treatment: A Promising Widely Used Therapy with Unintended Adverse Consequences

Herbst

Anderson

2015

AMA Journal of Ethics

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Diethylstilbestrol (DES) was first synthesized in 1938 and was the first orally active nonsteroidal estrogen that could be used for human therapy [1]. At that time, endocrinology was in its infancy and this discovery was a unique and great advance. Recurrent pregnancy loss was a serious medical problem then as it is now. It was believed the problems were due to a faulty hormonal environment of the fetal-placental unit, rather than primarily to genetic causes, as we have subsequently learned. There were studies at that time indicating that compromised pregnancies had a deficient output of the hormone progesterone, and further studies conducted in the late 1940s in Boston using very crude measuring techniques suggested that this deficiency could be corrected by administering DES to the mother, which would then lead to a healthy pregnancy. These studies led to the widespread usage of the drug to prevent pregnancy loss [2][3][4].The initial examination of the newborns born to mothers treated with DES during pregnancy showed no abnormalities (C. Smith, personal communication). The treatment, however, was controversial. (A unique double-blind study conducted at the University of Chicago in the early 1950s failed to show any improved pregnancy outcome with DES therapy [5]. This study, while negative, was conducted on a healthy pregnant population, which was different than the Boston Study, which was conducted on a high-risk population with a history of bleeding in pregnancy or multiple pregnancy losses.) An additional problem is that the hormone assays in the Boston Study were later found to be faulty and not to actually measure progesterone (Louis L. Engel, PhD, personal communication). It is believed that DES continued to be heavily used in the 1960s, and it has been estimated that 2 to 4 million women in the United States took DES during pregnancy [6].Then, in the late 1960s, eight extraordinarily rare cases of clear cell adenocarcinoma (CCA) of the vagina were diagnosed and treated in women in their teens and early 20s in the Boston area [7]. No such cluster of cases in young patients had ever been seen previously. CCA of the vagina was known to be a cancer that rarely occurred even in older women. In an effort to understand the cause of this cluster, a case-control study was conducted at the Massachusetts General Hospital in 1971 that linked the appearance of these cancers to the patients' mothers having been treated with DES for pregnancy

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“…Routine vaginal cytology is often negative, and the tumors frequently cannot be palpated on examination, making diagnosis challenging. The possibility of a vaginal tumor must be considered in the differential diagnosis of prolonged vaginal bleeding, especially if the bleeding does not respond to hormone therapy in cases of adult women [11]. Most CCACs are of Müllerian origin.…”

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A case of clear cell adenocarcinoma in the uterine cervix of 52-year-old virgin

Lee

Chang

Kyung

et al. 2012

Korean J Obstet Gynecol

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Clear cell adenocarcinoma (CCAC) of uterine cervix is very rare tumor and only 4%-9% of entire adenocarcinoma appears to be diagnosed as clear cell type. Risk factors and pathogenesis of this disease are not exactly revealed. The intrauterine exposure to diethylstilbestrol (DES) and associated non-steroidal estrogen during pregnancy before 18 weeks is the only known risk factor, and also hormonal changes or genetic causes are suggested as the risk factors. We report a case of CCAC in the uterine cervix of 52-year-old virgin who had never been exposed to DES, with a brief review of related literature. Copyright © 2012. Korean Society of Obstetrics and GynecologyClear cell adenocarcinoma (CCAC) of the uterine cervix is a rare disease accounting for only 4% of all adenocarcinomas of the uterine cervix. Though the etiology and pathogenesis are not clear, several studies have linked the occurrence of vaginal CCAC in young women with intrauterine exposure to the synthetic nonsteroidal estrogenic hormone, diethylstilbestrol (DES). Other factors reported to be associated with the development of CCAC are microsatellite instability, human papillomavirus infection, bcl-2 protein overexpression, and p53 gene mutation. CCAC is refractory to chemotherapy or radiation therapy, and its prognosis is poorer than that of squamous cell carcinoma of the same organ. We experienced a case of CCAC in the uterine cervix of 52-yearold virgin who had never been exposed to DES and report this case with a brief review of related literature. Case ReportA 52-year-old woman had suffered vaginal spotting for about 3 months. She visited a local gynecologist and liquid based cytology (Papanicolaou smear) was done at uterine cervix by the gynecologist. The cytology showed atypical endocervical cells that favored neoplastic changes, which then she was referred to our outpatient department for further evaluation and management. She had no history of coitus and had never been exposed to in utero exogenous steroid hormone. The vaginal examination and inspection showed caulifl ower-like mass of the cervix (Fig. 1). On rectal examination, the left parametrium was free and right parametrium was moderately thickened. High-risk human papillomavirus (hrHPV) test at uterine cervix done by hybrid capture II was negative. Histological diagnosis by punch biopsy was CCAC of the uterine cervix. Magnetic resonance imaging showed a solid mass, 1.6×2.9×2.5 cm in diameter (Fig. 2). This solid mass was protruding from the posterior lip of the cervix and extending to the upper vagina. Positron emission tomography-computed tomography was also performed, and there was evidence of tumor expansion neither to parametrium nor to endometrium. No involvement of pelvic and para-aortic lymph nodes was found. Parameters from blood chemistry studies and the levels of tumor markers were all CASE REPORT Korean J Obstet Gynecol 2012;55(3):192-196 http://dx

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Adenocarcinoma of the vagina in adolescence.A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas)

Cited by 407 publications

References 21 publications

The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy

The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy

Diethylstilbestrol (DES) Pregnancy Treatment: A Promising Widely Used Therapy with Unintended Adverse Consequences

A case of clear cell adenocarcinoma in the uterine cervix of 52-year-old virgin

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