Vulva & vagina

• ICD-10:
  • N89.8 - other specified noninflammatory disorders of vagina
  • N89.9 - noninflammatory disorder of vagina, unspecified

• Diethylstilbestrol causes irregularities in p63 gene expression, which determines whether Müllerian duct epithelium becomes uterine or vaginal cells and leads to vaginal adenosis
• Mouse model of diethylstilbestrol exposure demonstrates vaginal adenosis and structural changes similar to actual changes observed in women (Hum Pathol 1982;13:190)
• Pathophysiology of non-diethylstilbestrol related adenosis has not been determined conclusively; however, it may result from p63 gene expression changes in squamous epithelium or Müllerian remnants upon epithelial damage or from implantation of Müllerian derived columnar cells into vaginal lesions during menstruation
  • Glandular proliferation in adenosis is regulated by estrogen (Rev Obstet Gynecol 2011;4:81)

• Usually asymptomatic, although vaginal discharge or postcoital bleeding or dyspareunia have been reported (Mutter: Pathology of the Female Reproductive Tract, 3rd Edition, 2014)
• Vaginal mucosa displays red granular spots or patches and fails to stain with an iodine solution (Mutter: Pathology of the Female Reproductive Tract, 3rd Edition, 2014)
• Mosaicism and punctation are common findings during colposcopy (Obstet Gynecol 1978;52:457)

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• 2 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
• References: Mutter: Pathology of the Female Reproductive Tract, 3rd Edition, 2014, Kurman: Blaustein's Pathology of the Female Genital Tract, 6th Edition, 2011

Contributed by Leonel Maldonado, M.D.

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

Contributed by Leonel Maldonado, M.D.

• 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 much more closely resemble those of normal endometrium than the glands seen in adenosis
  • 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)

• Sternberg: Diagnostic Surgical Pathology, 5th Edition, 2009, DeMay: The Art & Science of Cytopathology, 2nd Edition, 2011

A 28 year old woman presents with persistent vaginal discharge and is found to have submucosal mucinous glands on a vaginal biopsy. What is the most likely scenario?

1. Maternal grandmother's use of diethylstilbestrol (DES) caused in utero exposure for the patient’s mother
2. Maternal use of DES caused in utero exposure for the patient
3. The patient had prior treatment for bacterial vaginosis
4. The patient had prior treatment for vaginal condyloma acuminata
5. Use of DES by the patient

D. The patient had prior treatment for vaginal condyloma acuminata. Vaginal application of 5-fluoruracil and vaginal CO2 laser therapy (common treatments for condyloma acuminata) are 2 known non-DES causes for vaginal adenosis. Answer C is incorrect because these are not common treatments for bacterial vaginosis. Answers A, B and E are incorrect because in utero exposure to diethylstilbestrol (DES) was the most common cause of vaginal adenosis for women born in the middle of the 20th century but DES exposure is not a concern in this patient who was born long after its discontinued use.

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Reference: Vaginal adenosis

Which statement concerning vaginal adenosis is true?

1. Inapparent on gross examination
2. May be associated with microglandular hyperplasia
3. Progresses to adenocarcinoma in a majority of the cases
4. Usually manifests in prepubertal age
5. Usually related to bacterial vaginosis

B. May be associated with microglandular hyperplasia. Vaginal adenosis commonly appears as red nodules / red granular spots or patches and fails to stain with an iodine solution on colposcopy. Mosaicism and punctation are common findings during colposcopy. It commonly manifests as excessive mucous discharge in postpubertal age. Vaginal adenosis seldom progresses to cancer. Microglandular hyperplasia develops in foci of vaginal adenosis, especially after oral contraceptive use. Microglandular hyperplasia may be confused with clear cell adenocarcinoma (which is also diethylstilbestrol associated).

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Reference: Vaginal adenosis