Clear-cell carcinoma of the vagina

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Clear-cell carcinoma of the vagina
SpecialtyOncology, gynecology

Clear-cell carcinoma of the vagina (CCC) is a type of glandular vaginal cancer that presents with vaginal bleeding or discharge typically in older females, though was formerly seen in younger women linked to prenatal to diethylstilbestrol (DES), a drug which was once prescribed in pregnancy.[1] Since the discontinuation of DES, associated conditions include adenomyosis and endometriosis.[1]

CCC most frequently occurs in the upper third of the front of the vagina.[1]

It is a rare.[1]


After age 30 it was thought that women exposed prenatally, "DES daughters", were no longer at risk for the disease, but as they age into their 40s and 50, cases continue to be reported.[2]

According to the Centers for Disease Control and Prevention (CDC), DES daughters should have a pap/pelvic exam every year because of their lifelong risk for clear-cell adenocarcinoma.[3][4]


Clear-cell adenocarcinoma of the vagina is a rare cancer, occurring in up to 10% of primary vaginal malignancies. It is all but confirmed if maternal use of DES is established. Even though it was once thought to no longer occur past the age of 30, it is still seen in the 40s and 50s. Some of the main signs and symptoms for clear-cell adenocarcinoma of the vagina are spotting between menstrual cycles, bleeding post-menopause, abnormal bleeding, and malignant pericardial effusion or cardiac tamponade.[5]


Low grade cancer is treated by surgical resection. High grade will require neoadjuvant chemotherapy and resection. Long-term surveillance will be required.[5]


The synthetic estrogen DES was given to millions of pregnant women in the United States and other countries. Use in the US was primarily from 1938 to 1971 but not limited to those years. Internationally, DES use continued until the early 1980s. DES was given if a woman had a previous miscarriage, diabetes, or a pregnancy with bleeding, threatened miscarriage or premature labor.

Up until the mid to late 1950s some women were given DES shots. After that, DES was primarily prescribed in pill form. DES also was included in some prenatal vitamins.[citation needed]

In the late 1960s through 1971 a cluster of young women, from their teens into their twenties, was mysteriously diagnosed with clear-cell adenocarcinoma (CCA), a cancer not generally found in women until after menopause. Doctors at Massachusetts General Hospital eventually linked DES exposure before birth to the development of CCA in these young women. They determined the risk for developing CCA among DES daughters is estimated at 1 in a 1,000.[6]

See also


  1. 1.0 1.1 1.2 1.3 1.4 WHO Classification of Tumours Editorial Board, ed. (2020). "9. Tumours of the vagina: clear-cell carcinoma of the vagina". Female genital tumours: WHO Classification of Tumours. Vol. 4 (5th ed.). Lyon (France): International Agency for Research on Cancer. p. 409. ISBN 978-92-832-4504-9. Archived from the original on 2022-06-17. Retrieved 2023-10-21.
  2. Smith, Emily K.; White, Mary C.; Weir, Hannah K.; Peipins, Lucy A.; Thompson, Trevor D. (1 January 2012). "Higher incidence of clear cell adenocarcinoma of the cervix and vagina among women born between 1947 and 1971 in the United States". Cancer Causes & Control. SpringerLink. 23 (1): 207–211. doi:10.1007/s10552-011-9855-z. PMC 3230753. PMID 22015647.
  3. "Annual Exam for DES Daughters" (PDF). Centers for Disease Control and Prevention. Archived from the original (PDF) on 4 October 2013. Retrieved 18 June 2013.
  4. Moyer, Virginia A.; U.S. Preventive Services Task Force (19 June 2012). "Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement". Annals of Internal Medicine. 156 (12): 880–91, W312. doi:10.7326/0003-4819-156-12-201206190-00424. PMID 22711081.
  5. 5.0 5.1 Gera S. Clear cell adenocarcinoma. website. Archived 2018-01-05 at the Wayback Machine. Accessed May 25th, 2019
  6. Hatch EE, Palmer JR, Titus-Ernstoff L, et al. (August 1998). "Cancer risk in women exposed to diethylstilbestrol in utero". JAMA. 280 (7): 630–4. doi:10.1001/jama.280.7.630. PMID 9718055. Archived from the original on 2020-03-14. Retrieved 2023-06-15.

 This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".