Benign / nonneoplastic epithelial lesions


Topic Completed: 2 September 2002

Minor changes: 13 November 2020

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Adenosis [title]

Leonel Maldonado Gonzalez, M.D.
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Cite this page: Maldonado L. Adenosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixadenosis.html. Accessed December 3rd, 2021.
Definition / general
  • "Vaginal adenosis" refers to the persistence of Müllerian glandular epithelium in the vagina after birth
  • First described in 1877 by von Preuschen
  • Most well known for its association with diethylstilbestrol (DES) use during pregnancy (to prevent a threatened abortion) by mothers of affected young women during the mid 1940s and 1950s
    • Present in 35% to 90% after in utero exposure to DES (100% have adenosis if DES started before gestational week 8, 6% if started week 15 or later)
  • DES adenosis is similar histologically to non DES adenosis
  • Mouse model of DES exposure demonstrates vaginal adenosis and structural changes similar to actual changes observed in women (Hum Pathol 1982;13:190)
Essential features
  • Strong association with DES exposure in utero (with incidence decreasing after discontinuation), although other causes have been reported
  • Most common type is mucinous, with endocervical-like glands present; tuboendometrial glands can also be present
  • Women are at risk of neoplasia, including clear cell adenocarcinoma, as well as squamous dysplasia
ICD coding
  • N89.8 Other specified noninflammatory disorders of vagina
  • N89.9 Noninflammatory disorder of vagina, unspecified
  • An estimated 5 to 10 million women in the United States received DES during pregnancy
  • Approximately one fifth of women who were exposed in utero to DES demonstrate gross structural changes in the cervix or vagina including vaginal adenosis
  • Vaginal adenosis has also been reported in 2 - 10% of nonexposed females
  • Involves the upper third of the vagina (34% of DES exposed cases), with the anterior wall more frequently involved than the posterior wall
  • Middle third (9% of cases) and lower third (2% of cases) may be involved
  • DES causes irregularities in p63 gene expression, which determines whether Müllerian duct epithelium becomes uterine or vaginal cells, leading to vaginal adenosis
  • Diethylstilbestrol (DES), a synthetic, nonsteroidal estrogen, profoundly affects the development of the vagina, uterus and fallopian tubes
  • Today, in the post DES era, vaginal adenosis usually occurs in women exposed to other hormones, drugs, trauma, inflammation, laser, radiation or chemotherapy (5-Fluorouracil)
Clinical features
  • Usually asymptomatic, although vaginal discharge or postcoital bleeding or dyspareunia have been reported
  • The vaginal mucosa displays red granular spots or patches and fails to stain with an iodine solution
  • Mosaicism and punctuation are common findings during colposcopy
Case reports
Gross description
  • The vaginal mucosa displays cysts or red granular spots or patches
Microscopic (histologic) description
  • Two adult (differentiated) forms of adenosis have been described:
    • Mucinous: most common type of adenosis (62% of biopsy specimens); characterized by mucinous columnar cells that resemble those of the normal endocervical mucosa
    • Tuboendometrial: found in 21% of specimens; glands are lined by light and dark cells, often ciliated and resemble fallopian tube and endometrial gland cells
    • Embryonic: glands composed of low columnar or cuboid cells
  • Glands may be simple, complex, cystic or papillary and usually found in the lamina propria, but also on the mucosal surface
  • Cysts lined by a single layer of columnar mucinous cells may resemble cervical nabothian cysts
  • Squamous metaplasia can be present and represents the process by which adenosis transforms and heals
  • Rarely, intestinal metaplasia may be seen
Microscopic (histologic) images

Contributed by Leonel Maldonado, M.D.
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Vaginal wall lesion biopsy

Cytology description
  • Vaginal specimens are characterized by endocervical-like glandular cells or metaplastic squamous cells
  • Endometrioid glandular cells can also occur
Cytology images

Contributed by Leonel Maldonado, M.D.
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Benign appearing grandular cells

Differential diagnosis
  • Clear cell adenocarcinoma (vagina): may be confused with the glands of adenosis that undergo microglandular hyperplasia (small, uniform, crowded glands without mucin, nuclear pleomorphism and prominent nucleoli)
  • Endometriosis: presence of endometrial stroma with glands that resemble much more closely those of normal endometrium than the glands seen in adenosis; a CD10 is useful to confirm the presence of endometrial stroma
  • Mesonephric (Wolffian) remnants: mesonephric tubules are lined by nonciliated, nonmucinous cuboid cells with dense, eosinophilic luminal secretions; these remnants are surrounded by a loose fibrovascular stroma that may contain smooth muscle fibers
  • Recurrent endometrial adenocarcinoma: glandular cells in vaginal cytology Papanicolaou tests in patients with hysterectomy for endometrial adenocarcinoma (Diagn Cytopathol 2012;40:138)
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