General
=========================================================================

• Vaginal intraepithelial neoplasia (VAIN) is defined as presence of squamous cell dysplasia without invasion

Epidemiology
=========================================================================

• True incidence of VAIN is unknown, but is estimated in US at 0.1 cases per 100,000 women (J Womens Health (Larchmt) 2009;18:1731)
• Mean age ~50-60 years, although can occur over a wide age range (22-80 years) (Acta Obstet Gynecol Scand 1999;78:648, J Obstet Gynaecol Res 2010;36:94)

Sites
=========================================================================

• More common in upper third of the vagina (J Obstet Gynaecol Res 2010;36:94)

Etiology
=========================================================================

• HPV has been implicated in pathogenesis of VAIN
• HPV associated lesions are often multifocal and multicentric
• Prevalence of HPV in VAIN 2/3 and VAIN1 is 92.6%, and 98.5%, respectively, higher than in vulvar lesions (Obstet Gynecol 2009;113:917)
• HPV16 is most common HPV type in vaginal (55.4%) cancers and VAIN2/3 (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

Diagnosis
=========================================================================

• 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 VAIN2/3 (J Obstet Gynaecol Res 2010;36:94)
• Lugol's 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
=========================================================================

• Intraepithelial vaginal neoplasia following immunosuppressive therapy treated with topical 5-FU (Obstet Gynecol 1975;46:360)

Treatment
=========================================================================

• 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
  • Topical application of therapeutic agents has the advantage of treating the entire vaginal mucosa with good coverage of multifocal disease and disease in folds and recesses of the vagina
  • Imiquimod 5% cream is commonly used (Int J Gynaecol Obstet 2008;101:3, Int J Gynecol Cancer 2005;15:898, J Low Genit Tract Dis 2003;7:290, J Low Genit Tract Dis 2012;16:306)
  • Complications of topical 5-FU include vaginal irritation or burning and ulcerations (Obstet Gynecol 1981;58:580)
• 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)

Micro 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 VAIN3
• Low grade VAIN comprises VAIN 1 and high grade includes VAIN 2 and 3

Micro images
=========================================================================

Mild squamous dysplasia, VAIN I

Moderate squamous dysplasia, VAIN II

Severe squamous dysplasia, VAIN III

Squamous cell carcinoma in situ, VAIN III

Positive stains
=========================================================================

• 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
=========================================================================

• p16

Differential diagnosis
=========================================================================

• Urothelial (transitional) metaplasia

Additional references
=========================================================================

• Eur J Gynaecol Oncol 2006;27:638, J Fam Pract 1995;40:81, J Low Genit Tract Dis 2004;8:205

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).