Vulva, vagina & female urethra

Other carcinomas

Clear cell carcinoma

Last author update: 1 March 2014
Last staff update: 30 April 2021

Copyright: 2002-2023,, Inc.

PubMed Search: Clear cell adenocarcinoma [title] vagina

Shweta Gera, M.D.
Arzu Buyuk, M.D.
Page views in 2022: 3,229
Page views in 2023 to date: 2,528
Cite this page: Gera S, Buyuk A. Clear cell carcinoma. website. Accessed September 30th, 2023.
Definition / general
  • Most common subtype of vaginal adenocarcinoma associated with DES exposure in young females; can also occur in postmenopausal women without exposure to DES
  • DES causes persistence of Müllerian epithelium while inducing contact between epithelium and the vaginal mesenchyme
  • Unopposed estrogen and obesity causes increase in the peripheral conversion of steroid hormones to estrone by the enzyme aromatase leading to a hyperestrogenic environment (Gynecol Oncol 2006;103:1130)
Clinical features
Prognostic factors
Case reports
Clinical images

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Fig 1: not involving urethra or clitoris

Fig 2: not originating from cervix

Gross description
  • Superficially located polypoid, exophytic mass that typically originates from the anterior wall of the upper two thirds of the vagina (Gynecol Oncol 2007;105:273)
Microscopic (histologic) description
  • Tumor has cystic, papillary, tubular / glandular and solid architectural patterns with focal necrosis
  • Cells have distinct cell membranes, are large with moderate to abundant clear cytoplasm, occasionally may be oxyphilic
  • Cells are usually cuboidal and sometimes hobnail type with nuclei protruding into the lumen
  • Nuclei are round to irregular, hyperchromatic with conspicuous nucleoli (Int J Gynecol Pathol 2001;20:252)
Microscopic (histologic) images

Case #363



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Fig 3

Fig 4: papillae and acini in tubulocystic pattern

Cytology description
  • Provides diagnostic information in 41% of cases (Gynecol Oncol 2007;105:273)
  • Cells are arranged in sheets, clusters or papillae; cells have delicate vacuolated glycogen rich cytoplasm
  • May have naked nuclei and a tigroid background, similar to other glycogen containing tumor cells such as seminoma and Ewing sarcoma
  • Nuclei are large, pale and round with prominent nucleoli (Cytojournal 2013;10:17)
Cytology images

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Pap stain

Positive stains
Electron microscopy description
  • Similar ultrastructural features as CCA of ovary, cervix or endometrium
  • Glands have short, thick microvilli in the lumina; cells are attached by desmosomes and interdigitating cytoplasmic processes
  • Cells contain abundant glycogen granules, also many small, uniform mitochondria and "stacked" parallel rows of granular endoplasmic reticulum (Cancer 1972;29:1680, Cancer 1977;40:3019)
Molecular / cytogenetics description
  • p53 nuclear staining patterns is heterogeneous in both proportion and intensity of tumor cells stained (Gynecol Oncol 1996;60:339)
  • Overexpression of p53 protein is not due to mutational inactivation of the p53 gene but probably due to persistent DNA damage or genetic instability
  • Intrauterine exposure to DES, therefore, is unlikely to directly alter the p53 gene as has been suggested for other mutagens
  • Persistence of wild type p53 in these rare tumors may correlate with their typically favorable prognosis and radiosensitivity (Gynecol Oncol 1996;60:339)

Histopathology vagina - clear cell carcinoma

Differential diagnosis
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