Vulva, vagina & female urethra

Vaginal intraepithelial neoplasia (VAIN)

Topic Completed: 1 January 2015

Minor changes: 26 August 2020

Copyright: 2002-2021,, Inc.

PubMed Search: Vaginal intraepithelial neoplasia [title] VAIN

Shweta Gera, M.D.
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Cite this page: Gera S. Vaginal intraepithelial neoplasia (VAIN). website. Accessed December 3rd, 2021.
Definition / general
  • Vaginal intraepithelial neoplasia (VAIN) is defined as presence of squamous cell dysplasia without invasion
  • HPV has been implicated in pathogenesis of VAIN
  • HPV associated lesions are often multifocal and multicentric
  • Prevalence of HPV in VAIN 2 / 3 and VAIN 1 is 92.6% and 98.5%, respectively, higher than in vulvar lesions (Obstet Gynecol 2009;113:917)
  • HPV 16 is most common HPV type in vaginal (55.4%) cancers and VAIN 2 / 3 (65.8%) (Obstet Gynecol 2009;113:917)
  • History of prior pelvic radiation (7.4%), associated neoplasia of the lower genital tract (67.6%) and history of prior hysterectomy (54.4%) can be present (J Obstet Gynaecol Res 2010;36:94)
  • Arises from native squamous epithelium, not metaplastic epithelium as in cervix
Clinical features
  • VAIN is usually asymptomatic but may present with postcoital spotting or vaginal discharge
  • Most common presentation is abnormal cytology (J Obstet Gynaecol Res 2010;36:94)
  • Must exclude in all women with an abnormal Pap smear who had hysterectomy or who do not have identifiable cervical lesions that could account for the abnormality
  • VAIN is a histologic diagnosis, typically based on colposcopic assessment and biopsy of the vagina
  • With application of 3 - 5% acetic acid, lesions appear as raised or flat white, granular epithelium with sharply demarcated borders with punctation and mosaic pattern more prevalent in VAIN 2 / 3 (J Obstet Gynaecol Res 2010;36:94)
  • Lugol iodine solution can be used to detect lesions and confirm boundaries prior to excision
Prognostic factors
  • High grade VAIN is a precursor to invasive squamous cell carcinoma of the vagina
Case reports
  • Surgical excision is the mainstay of VAIN treatment (J Low Genit Tract Dis 2012;16:306)
    • Surgical approaches include local excision, partial vaginectomy; rarely total vaginectomy for extensive and persistent disease
    • Partial or total vaginectomy appears to be the safest method of treating multifocal high grade VAIN
    • Complications include shortening or stenosis of the vagina following wide local excision and significant postoperative morbidity following abdominal procedures
  • CO2 laser therapy is also used for local tissue ablation, with pain and bleeding the most frequent complications (J Reprod Med 1990;35:941)
    • Ablative therapy should not be performed if the entire area of abnormal epithelium cannot be visualized or if there is any suspicion of invasion thorough colposcopy
  • Medical therapy
  • Radiation therapy includes high dose brachytherapy (Gynecol Oncol 1997;65:74)
  • Conservative options in the form of laser ablation and topical agents are useful as first line treatment methods especially in young women and for multifocal disease
  • Radical options like brachytherapy and vaginectomy should be reserved for highly selected cases (J Low Genit Tract Dis 2012;16:306)
Microscopic (histologic) description
  • VAIN is classified in a similar manner to CIN:
    • VAIN 1: mild dysplasia
    • VAIN 2: moderate dysplasia
    • VAIN 3: severe dysplasia / carcinoma in situ
  • It is classified according to the depth of epithelial involvement:
    • VAIN 1 involves lower one third of epithelium
    • VAIN 2 involves lower two thirds of epithelium
    • VAIN 3 involves more than two thirds of epithelium
      • Carcinoma in situ, which encompasses the full thickness of the epithelium, is included under VAIN 3
  • Low grade VAIN comprises VAIN 1 and high grade includes VAIN 2 and 3
Cytology description
  • Cytological features are similar to cervical Pap smear
  • Low grade: nuclei are enlarged at least 3 - 4 times that of the normal intermediate cell nucleus, with HPV cytopathic changes including distinct cytoplasmic halo and binucleation or multinucleation
  • High grade: high N/C ratio, immature cytoplasm and greater nuclear pleomorphism
Positive stains
Differential diagnosis
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