Vulva & vagina
Squamous carcinoma and precursor lesions
Vaginal intraepithelial neoplasia (VAIN)
Authors: Shweta Gera, M.D., Arzu Buyuk, M.D.
Last author update: 1 January 2015
Last staff update: 16 April 2024 (update in progress)
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: Vaginal intraepithelial neoplasia [title] VAIN
Table of Contents
Definition / general | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Cytology description | Positive stains | Differential diagnosis | Additional referencesCite this page: Gera S. Vaginal intraepithelial neoplasia (VAIN). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/vaginavain.html. Accessed April 25th, 2024.
Definition / 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 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
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 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
- 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)
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
Additional references
