VIN/VAIN O C T O B E R 3 RD 2 0 1 8 J M O R G A N
Vaginal Intraepithelial Neoplasia VAIN I, II, III Incidence 0.1/100,000 women in US Mean age 50s (J Womens Health (Larchmt) 2009:18:1731) (J Obstet Gynaecol Res 2010:36:94)
VAIN Risk Factors HPV HPV HPV HPV HPV HPV HPV HPV
VAIN Risk Factors HPV Smoking Immunosuppresion Pelvic radiation (J Obstet Gynaecol Res 2010:36:94)
VAIN- Smoking Nicotine, cotinine and tars detected in cervical secretions of smokers Mutogenic activity demonstrated in cervical cells Decreased number of antigen presenting Langerhans cells in epithelium Similar pathology presumed for vaginal dysplasia
VAIN- Immunosuppression Transplant recipient HIV/AIDS Systemic inflammatory conditions RA SLE Treatments for connective tissue/systemic inflammatory conditions DMARDs Steroids Humira etc
VAIN HPV HPV present in 98.5% VAIN 1 92.6% VAIN 2/3 HPV 16 present in 65.8% VAIN 2/3 55.4% vaginal cancers (Obstet Gynecol 2009:113:917)
VAIN Squamous cell dysplasia, without invasion 1- Lower 1/3 of epithelium 2- Lower 2/3 of epithelium 3- More than 2/3 of epithelium involved Includes CIS- full thickness
VAIN- Location Upper 1/3 Distal 1/3 Mid vagina More commonly seen in patients with prior hysterectomy May be isolated or multifocal lesions
VAIN-Presentation Asymptomatic Abnormal pap screening Vaginal discharge Postcoital bleeding or discharge
VAIN Diagnosis Histological Colposcopy and biopsy 5% Acetic Acid- longer application needed Lugols Iodine Directed biopsy
VAIN Colposcopic Findings White flat granular lesion Sharp demarcated border Punctation Mosaicism Contact bleeding
VAIN I Very high association with high risk HPV Unclear link to invasive malignancy Conservative management
VAIN 2/3 Premalignant Condition Typically Treated??
VAIN 2/3 Treatment Surgery Excisional Ablative Medical Radiation
Excisional Surgery Local excision Small isolated lesion Distal lesion Partial vaginectomy Total vaginectomy Shortening or stenosis of vagina Dysparuenia Fistula formation
Ablative Surgery CO2 laser ablation Paired colposcope and micromanipulator Do not use if any concern for invasive disease
Medical Therapy Good for multifocal disease. Able to reach nooks/folds Imiquimod 5% 5 FU TCA
Imiquimod Immune response mediator Self administered weekly titrating up to 3x weekly 8 weeks course Irritative symptoms common 50% response rate
5 FU 1gm PV weekly x 8 weeks 30-80% recurrence risk Good for multifocal lesions Vaginal ulceration, burning and irritation oftens requires treament break or cessation
TCA 50% TCA Keratolytic agent Weekly application up to 4 weeks Good for focal lesion 50% clearance of VAIN 2/3
Radiation Vaginal brachytherapy Generally not recommended for preinvasive disease Increased risk for secondary malignancy and difficulty assessing vaginal mucosa/future paps
Diethylstilbestrol Nonsteroidal estrogen In US used 1941-1971 (peak 1940s-50s) Marketed to improved pregnancy outcomes Vaginal epithelial changes Altered replacement of mullerian derived epithelium with squamous epithelium as urogenital sinus developed Structural anomalies of cervix and upper genital tract
DES Vaginal Epithelial Changes Adenosis Epithelium of Mullerian origin Squamous metaplasia Immature metaplasia Incidence 34-65% Study dependant (Obstet Gynecol 1979:53:300)
DES Vaginal Epithelial Changes Severity linked to Earlier gestational age at initial exposure Dose Duration of exposure
DES Structural Changes Vagina Absent or shortened fornix Vaginal stricture Cervix Collar Coxcomb Pseudopolyp Hypoplastic cervix 25-43% of DES exposed patients (Am J Obstet Gynecol 1894:148:59)
DES Clear Cell Carcinoma of the Vagina 60% of clear cell vaginal and cervical carcinoma patients with history of in-utero DES exposure (Herbst et al 1971) <1 per 1,000 DES exposed women developed clear cell carcinoma Mean age at diagnosis 19yo Diagnosis peaked 1975
VIN
Vulva Intraepithelial Neoplasia VIN I, 2, 3 Poorly reproducible diagnosis VIN 1 never shown to have malignant potential 2 class system Low vs High grade VIN More reproducible No link shown between low grade and high grade lesions
VIN 1 Diagnosed whenever atypical cells seen on lower 1/3 of normal or hyperplastic squamous epithelium Wide variety of dermatologic conditions No link to vulvar neoplasia May include Lichen sclerosus Lichen simplex chronicus Lichen planus Psoriasis Candidiasis Contact dermatitis Condyloma Vulvar vestibulitis
VIN Usual Type More common HPV related Think cervical dysplasia/cancer risk factors Differentiated Post menopausal Associated with chronic inflammatory conditions Lichen Sclerosus
VIN Rising Incidence Bimodal age distribution Rising incidence in younger women 3-9% risk of vulvar carcinoma developing without treatment
VIN Risk Factors HPV Chronic inflammatory or irritative local conditions Smoking Other genital tract dysplasia Other STD exposure Immunosuppression
Symptoms?? VIN Presentation
VIN Symptoms Recurrent yeast infection Itch Irritation Sore Lump Bump
VIN Associated with other genital HPV diseases Look for stigmata of other vulvar conditions If don t treat lichen sclerosus or cause of lichen simplex chronicus, then higher recurrence risk
VIN Diagnosis Examination important but not diagnostic Biopsy Full thickness Keyes Punch Biopsy each lesion if multiple lesions present Biopsy worst appearing area
Vulvar colposcopy All clinically significant lesions can be seen with naked eye Colposcopic exam may help define margins or identify subclinically involved areas when planning treatment Thicker epithelium Allow acetic acid application for 3-5 minutes
VIN Treatment Surgical excision Laser Ablation Medical Therapy
VIN Surgery Wide local excision Excision of visibly abnormal tissue and margin of normal appearing tissue Full thickness of epithelium Painful, risk of infection, stenosis, scarring. Tissue available for pathologic assessment 12-25% risk of occult malignancy in some studies reported
VIN Laser ablation CO2 laser ablation Full thickness ablation of epithelium to third surgical plane Higher recurrence risk Less disfugurement/loss of function No pathologic assessment of tissue
Imiquimod Topical 3x weekly treatment Dependant on patient compliance Local ulceration/pain Treatment break may be needed
Recurrence risk Approx 30% 25 months median (range 1.6-326 months) Treatment failure vs Field Effect Higher recurrence risk with Larger primary lesion Positive margin Tobacco use Laser ablation vs surgical excision or imquimod
Recurrence Risk Higher recurrence risk with Larger primary lesion Positive margin Tobacco use Laser ablation vs surgical excision or imquimod
Recurrence Risk Primary Treatment Modality Recurrence Rate ( %) Excision 26.7 Laser 45 Imiquimod 13.6 Retrospective study at MDACC Not controlled for lesion size, number or location and primary treatment choice or provider Combination of excision and laser had highest recurrence risk (Gyn Oncol 127(2012)312-315
Questions