Tag: CCAC

Rates and risks of DES-related clear-cell adenocarcinoma of the vagina and cervix

CCAC update, Dr Arthur Herbst, 1987

clear_cell_carcinoma image
DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced for consumption.

1987 Study Abstract

We reviewed 519 cases of clear-cell adenocarcinoma of the vagina and cervix identified by the Registry for Research on Hormonal Transplacental Carcinogenesis of the University of Chicago through June 30, 1985. In 60 percent of all cases the patient’s mother had received diethylstilbestrol during pregnancy. An additional 12 percent of all mothers had been treated with another hormone or with an unidentified medication. Ninety-one percent of the cases in diethylstilbestrol-exposed women were diagnosed when the patient was between the ages of 15 and 27. The median age at diagnosis was 19.0 years. The risk that clear-cell adenocarcinoma will develop in an exposed female from birth through age 34 is 1 case per 1000 women. The temporal pattern of occurrence of clear-cell adenocarcinoma corresponds closely with that of the use of diethylstilbestrol for pregnancy support in the United States. The rarity of this tumor among exposed women suggests that diethylstilbestrol is not a complete carcinogen and that some other factor is also involved in the pathogenesis of clear-cell adenocarcinoma of the vagina and cervix.

Sources and more information
  • Rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix. An update., Melnick S, Cole P, Anderson D, Herbst A., N Engl J Med. 1987 Feb 26;316(9):514-6, NCBI Pubmed PMID: 3807995.
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Very late recurrence of DES-related clear cell carcinoma of the cervix

Long term surveillance of DES exposed women is a must

image of clear-cell-carcinoma-of-the-cervix
This 2015 case demonstrates the need and the importance for continued and frequent follow-up examination in individuals prenatally exposed to diethylstilbestrol.

2015 Study Abstract

Clear cell adenocarcinoma of the cervix is a rare tumor of the lower genital tract. It has been described in young women with a history of intra uterine exposure to diethylstilbestrol. This tumor is characterized by a greater tendency for late recurrences. In this article, we report the case of one exposed-patient who developed recurrence as liver metastases, 24 years after the initial treatment. This case demonstrates the need and the importance for continued follow-up in individuals prenatally exposed to diethylstilbestrol.

2015 Study Conclusions

To summarize, this case represents the longest reported disease-free interval till recurrence and the first description of metastatic liver disease of DES related clear cell adenocarcinoma of the cervix. It reemphasizes the necessity of long term surveillance of DES exposed women and confirms previous reports recommending the importance of frequent follow-up examination not only of the pelvis but also of all distant potential sites of metastasis. It also shows that treatment with paclitaxel, carboplatin and bevacizumab can be an effective and safe therapeutic option for treating recurrence of this rare tumor.

Sources and more information
  • Very late recurrence of Diethylstilbestrol – related clear cell carcinoma of the cervix: case report,Ablavi Adani-Ifè, Emma Goldschmidt, Pasquale Innominato, Ayhan Ulusakarya, Hassan Errihani, Philippe Bertheau and Jean François Morère, Gynecologic Oncology Research and Practice 2015, $article.volume.volumeNumber:3 doi:10.1186/s40661-015-0010-5, gynoncrp.com/content/2/1/3, 17 July 2015.
  • Gynecologic Oncology Research and Practice PDF case report.
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Clear cell carcinoma of the cervix: a multi-institutional review in the post-DES era

Patients with low risk early stage CCCC may be managed with radical surgery alone

Cervix Normal Squamocolumnar Junction
This 2008 study results suggest that patients with low risk early stage CCCC may be managed with radical surgery alone, without the need for adjuvant chemotherapy or radiation.
Cervix: Normal Squamocolumnar Junction image by Ed Uthman.

2008 Study Abstract

Objective
To conduct an outcome analysis of patients with cervical clear cell carcinoma (CCCC) in the post-DES era.

Methods
A retrospective review was conducted at 3 major gynecologic cancer centers of all primary CCCC between 1982 and 2004.

Results
CCCC was confirmed in 34 patients. Median age was 53 years. DES exposure was confirmed in 2 (6%) patients. A history of smoking was elicited in 22%, and of abnormal Pap smear 18% patients. Primary surgical resection was performed in all stage I or IIA patients (n=26); they displayed superior 3-year overall survival (OS) compared to advanced stage (n=8) patients (91% vs. 22%, p<0.001). Pelvic lymph node involvement was noted in 25%; all patients with positive para-aortic nodes (20% of patients sampled) had positive pelvic nodes. All node positive patients were treated with adjuvant radiation, but nevertheless displayed reduced progression free (31% vs 92%, p<0.001) and overall survival (80% vs. 100%, p=0.02). Adjuvant radiotherapy did not appear to impact OS in patients with negative lymph nodes.

Discussion
This series provides insight into the management of early stage CCCC in the post-DES era. Although these patients may be at slightly higher risk of nodal spread, clear cell histology by itself does not appear to portend a worse prognosis than squamous cell carcinoma of the cervix in the absence of traditional risk factors. Our data suggest that patients with low risk early stage CCCC may be managed with radical surgery alone, without the need for adjuvant chemotherapy or radiation.

Sources and more information
  • Clear cell carcinoma of the cervix: A multi-institutional review in the post-DES era, M. Bijoy Thomas, Jason D. Wright, Aliza L. Leiser, Dennis S. Chi, David G. Mutch, Karl C. Podratz, and Sean C. Dowdya,, Gynecol Oncol. 10.1016/j.ygyno.2008.02.007, NCBI PMC3667392, 2008 Apr 3.
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Incidence of squamous neoplasia of the cervix and vagina in DES-exposed daughters

Association between in utero DES exposure and high-grade squamous neoplasia

2000 Study Abstract

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The 2000 study findings support an association between in utero DES exposure and high-grade squamous neoplasia

PURPOSE:
Women exposed to diethylstibestrol (DES) in utero are known to have an excess risk of clear cell adenocarcinoma of the vagina and cervix, in addition to vaginal epithelial changes, but the effect on the incidence of squamous neoplasia is uncertain. This study evaluated the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to diethylstilbestrol.

METHODS:
A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for thirteen years (1982-1995) for pathology-confirmed diagnoses of high-grade squamous neoplasia. A pathologist blinded to exposure status reviewed seventy-seven percent of cases. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (CI) controlling for age, calendar year, screening history and other covariates.

RESULTS:
The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.12 (1.19-3.77). Adjustment for screening history had little effect, but when the analysis was restricted to a group highly screened before 1982, the risk was reduced. Risk estimates were higher among women exposed earlier in gestation; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.82 (1.43-5.53).

CONCLUSIONS:
The findings support an association between in utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out..

Sources

  • Incidence of squamous neoplasia of the cervix and vagina in des-exposed daughters, NCBI, PMID: 11018391, Ann Epidemiol. 2000 Oct 1;10(7):467. Full text link.
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Ovarian Carcinoma in an Adolescent with TransGenerational Exposure to DiEthylStilbestrol

More transgenerational health risks posed by DES exposure

Abstract

image of PubMed NCBI The Endocrine Society logo
DES granddaughters with persistent abdominal pain even during childhood may need evaluation for genital tract abnormalities.

Small cell carcinoma of the ovary is rare in adolescence. The etiology of such tumors is unknown. Several reports suggest that transgenerational exposure to Diethylstilbestrol (DES) may have deleterious effects on the genitourinary tract.

The authors describe a 15-year-old girl with small cell carcinoma of the ovary whose maternal grandmother had been taking DES while she was pregnant with the patient’s mother.

This case, while anecdotal, suggests that a transgenerational history of DES exposure should be noted, and that granddaughters with persistent abdominal pain even during childhood may need evaluation for genital tract abnormalities.

Sources:
  • Ovarian carcinoma in an adolescent with transgenerational exposure to diethylstilbestrol, NCBI, PMID: 12902917, 2003 Aug;25(8):635-6.
  • Full text – Clinical and Laboratory Observations Volume 25 – Issue 8, Lippincott Williams & Wilkins, pp 635-636 2003.
  • Full text – A case of small cell carcinoma of the ovary hypercalcemic variant in a teenager, ScienceDirect, S2211338X12000622 2012.
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Gynaecological Cancers Information Leaflet

About five cancers that start in the female reproductive system

gynaecological cancers
Referring to five cancers that start in a woman’s reproductive system

The term gynaecological cancer refers to the five cancers that start in the female reproductive system:

Download The Eve Appeal Gynaecological Cancer Information Leaflet
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Cancer Risk in Women exposed to DiEthylStilbestrol in Utero

DES-exposed daughters need continued surveillance to determine whether any increases in cancer risk occur during the menopausal years

1998 Study Abstract

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DES-exposed daughters showed no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in the 1998 study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.

CONTEXT:
The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero.

OBJECTIVE:
To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up.

DESIGN:
A cohort study with mailed questionnaires and medical record review of reported cancer outcomes.

PARTICIPANTS:
A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s.

MAIN OUTCOME MEASURES:
Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters.

RESULTS:
To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result.

CONCLUSIONS:
Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.

Sources

  • Cancer risk in women prenatally exposed to diethylstilbestrol, NCBI, PMID: 9718055, 1998 Aug 19;280(7):630-4.
  • Full text JAMA. 1998;280(7):630-634. doi:10.1001/jama.280.7.630. link.
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Vaginal and Cervical Abnormalities, including CCA, related to PreNatal Exposure to Stilbestrol

In utero DES exposure associated with severe clear-cell adenocarcinoma in DES Daughters

Vaginal and cervical abnormalities, including clear-cell adenocarcinoma, related to prenatal exposure to stilbestrol
In utero exposure to Stilbestrol associated with severe clear-cell adenocarcinoma in DES Daughters

A variety of vaginal and cervical abnormalities have been encountered in the offspring of women who have taken stilbestrol or chemically related nonsteroidal estrogens during pregnancy.

Cervical erosion has been noted most often, but vaginal adenosis has been proven by biopsy in over 30 percent, and transverse vaginal and cervical ridges have been seen in approximately 10 percent of the exposed population. Although the use of these drugs had been widespread during the last two decades, the Registry of Clear-Cell Adenocarcinoma of the Genital Tract in Young Females has been able to collect only 170 cases of vaginal and cervical cancers of this type from all over the world.

It is important that cytologists and pathologists become familiar with the various non-enoplastic and neoplastic disorders related to these hormones in order that additional epidemiologic, clinical and pathological information be acquired without delay.

Sources: Vaginal and cervical abnormalities, including clear-cell adenocarcinoma, related to prenatal exposure to stilbestrol, NCBI, Dr Herbst A, Jul 1974.

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DiEthylStilbestrol and other Sex Hormones during Pregnancy

DES has terrible side-effects in DES Daughters, DES Sons, DES Grand-Children…

Diethylstilbestrol and other sex hormones during pregnancy
In utero exposure to Diethylstilbestrol is associated with terrible side-effects in DES Daughters, DES Sons, DES Grand-Children

Intrauterine exposure to diethylstilbestrol (DES) has been associated with this subsequent rare development of clear cell adenocarcinoma of the vagina and cervix in exposed female progeny. These tumors have been seen thus far in patients between the ages of 7 and 29 years. In addition, nonmalignant epithelial and structural genital alterations have been frequently observed. The epithelial changes of adenosis, ectropion, metaplasia, and potential neoplasia are considered. Thus far, no increased risk of squamous cell neoplasia has been demonstrated in DES-exposed subjects. However, increased pregnancy wastage, including premature birth, does appear to be more common among DES-exposed women; this increase may be related to the structural uterine and cervical changes that have occurred. DES-exposed men have been demonstrated to have anatomic genital changes, but the effects of these changes, if any, on male infertility are not known. Masculinization of the female external genitalia, including phallic enlargement and labioscrotal fusion, has been reported following intrauterine exposure to certain progestational agents and androgens.

Sources: Diethylstilbestrol and other sex hormones during pregnancy, NCBI, Dr Herbst A, Nov 1981.

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Correlation of Mother’s Recall of DiEthylStilbestrol History with obstetrical Records

The majority of these mothers who said they did not take DES were indeed DES positive by written records…

Clear cell adenocarcinoma of the lower genital tract. Correlation of mother's recall of diethylstilbestrol history with obstetrical records
Clear cell adenocarcinoma and mother’s recall of diethylstilbestrol history

The written obstetric records of maternal exposure to diethylstilbestrol (DES) were used as a criterion standard and compared with the DES exposure history recalled by mothers of women with vaginal, cervical, or indeterminable vaginal/exocervical clear cell adenocarcinoma.
Among cervical cases, the sensitivity of maternal recall was 50% (N = 2), and its specificity was 100%. Among vaginal and vaginal/exocervical cases, this sensitivity was 72%; specificity was 60%; and the majority of these mothers who said they did not take DES were DES positive by written records.
Thus investigators should avoid using maternal recall alone to measure DES exposure. Among subjects for whom written maternal obstetric records were available, 88% of vaginal cases and 46% of cervical cases were DES positive. The authors conclude that few cases of vaginal clear cell adenocarcinoma should occur in young women as the cohort of women exposed in utero to DES continues to age, whereas cases of cervical origin may continue to occur.

Sources: Clear cell adenocarcinoma of the lower genital tract. Correlation of mother’s recall of diethylstilbestrol history with obstetrical records, NCBI, Dr Herbst A, Nov 1990

See also: Are you a probable DES Daughter?
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