vulvar intraepithelial neoplasia ( vin ) is a dysplastic premalignant condition that affects the vulvar squamous epithelium . , vin may progress to invasive cancer within 17  years ( jones et al . , 2005 ) . although rare , vin has become an increasingly common problem in younger women <  50  years of age with a reported 392% increase in incidence from 19941997 ( joura et al . , 2000 ) . interestingly , it is not rare to diagnose invasive cancer at the time of surgery for vin , with a reported incidence of up to 5% ( acog , 2011 ) . a similar trend has been observed in vulvar cancer patients with a striking increase in incidence noted in the 4049  years age group ( joura et al . , 2000 ) . high risk human papillomavirus ( hpv ) infection , human immunodeficiency virus infection , smoking , and other pelvic neoplasia are some of the documented risk factors for development of vin ( acog , 2011 ) . recognized treatment modalities include partial superficial skinning vulvectomy , wide local excision , co2 laser ablation , topical ointments ( imiquimod 5% ) , and 5-aminolevulinic acid - based photodynamic therapy ( hillemanns et al . , 2006 ) . in 2006 , sinecatechins 15% ointment ( veregen , pharmaderm ) , was the first botanical drug approved by the food and drug administration for the treatment of external anogenital warts ( u.s . it is a formulation of a variety of catechins , a type of polyphenol with potent antioxidant activity . it has been identified for its immunostimulatory , antitumor , and antiproliferative properties  ( stockfleth et al . , 2008 ) . although veregen has an established role in complete clearance of anogenital warts ; it has not been used for the treatment of vin . we report a case of a woman with multifocal usual - type vin , warty type disease who was treated with sinecatechins 15% ointment . a 45-year - old female with myelodysplastic syndrome , 10  months after stem cell transplant ( cd4 count 143  cell / mcl ) , presented her primary care physician complaining of pruritic lesions on her vulva . an office biopsy was obtained which showed high grade vin and squamous cell carcinoma in situ ( cis ) . the patient was then referred to the gynecologic oncology service at our institution for further workup and management . she was noted to have extensive multifocal and multicentric disease ( fig .  1 ) . after performing further biopsies in the operating room , all biopsy specimens were then reviewed by our gynecologic pathologists and diagnosed as usual - type vin , warty subtype , with hpv changes and cis . however , due to its multifocal involvement and need for excision of the clitoris with extensive reconstruction , more conservative alternatives were considered . patient was followed every two weeks in clinic and after 8  weeks of treatment , she failed to show any clinical response . in addition , due to extreme pain with application , patient was unable to tolerate the full course , despite use of narcotics and pudendal block . consequently , we prescribed veregen ointment , to be used three times a day for six weeks . four weeks after start of therapy , visible improvement in the vulvar lesions was noted . the patient reported some pain and discomfort at the application sites , but stayed motivated to complete the treatment , as her lesions appeared to be resolving . at the end of 6  weeks , examination revealed complete resolution of all lesions , with mild scarring on the vulva ( fig .  2 ) . confirmatory biopsies of the scarred areas were taken and determined to be negative for dysplasia or carcinoma . she remains in remission after eleven follow up months and has resumed normal sexual function since then . throughout the last decade , incidence of vin in united states for women between ages 4049  years has increased to a current rate of 2.9 per 100,000 women . this increase has been attributed to a number of factors , including changes in sexual behavior , smoking habits , hpv infection , and increased surveillance ( joura et al . , 2000 ) . hpv 16 and 18 are associated with 7080% of vin lesions , and about 3040% of invasive vulvar cancers ( hillemanns et al . , 2006 ) . conversely , higher grade lesions may require aggressive surgical management to prevent progression to invasive cancer . in women with multifocal and extensive disease , laser ablation is an alternative to excisional therapy , provided there is no coexistent invasive cancer . although surgical treatment provides tissue sampling to evaluate for invasive cancer , medical management achieves preservation of vulvar anatomy and function , particularly in younger women . it is also recommended to prevent extensive excisional and reconstructive surgery in women that are not good candidates for surgery due to coexisting medical comorbidities or extensive , multifocal vulvar lesions . medical options that include imiquimod 5% applied three times weekly to affected areas for 1220  weeks is an effective therapy for high grade vin ( hillemanns et al . , 2006 ) . side effects related to its use include erythema , erosions , and moderate vulvar pain . imiquimod is a topical immune response modifier that acts by stimulating local cytokine production and cell mediated immunity , and thus has decreased effectiveness in immunocompromised patients . other available options for conservative treatment include 5-fluorouracil , topical 5-aminolevulinic acid based photodynamic therapy , and cidofovir ( antiviral agent ) ( acog , 2011 ) . our patient had extensive multifocal disease involving her clitoris that would require extensive surgical excision and reconstruction , repeated biopsies showed absence of invasive cancer , and it failed treatment with imiquimod 5% . the failure of response to imiquimod in our patient can be attributed to her low t cell count . we prescribed sinecatechins as an alternative to surgical treatment and followed her closely to monitor side effects , response , and signs of recurrence . sinecatechins , or polyphenol e compound , is a defined green tea extract , available with trade name veregen ( sinecatechin 15% ointment ) and is known to possess immunostimulatory , antiviral , antitumor and antiproliferative properties  ( stockfleth et al . , 2008 ) . it has a well - established role in complete clearance of anogenital warts when used three times daily for up to 16  weeks . three randomized , double blinded , placebo controlled trials have been published that prove the efficacy , safety and tolerability of sinecatechins in treatment of genital and perianal warts ( stockfleth et al . , 2008 ; gross et al . , 2007 ; tatti et al . , 2008 ) . when compared to other patient applied drugs like imiquimod 5% and 5-fluorouracil , sinecatechins was found superior in terms of clearance rates , cost , less recurrence rates and less patient discomfort ( tatti et al . , 2008 ) . minor local reactions like erythema , burning pain , pruritus were noted in 1020% of patients . the exact mechanism of action of sinecatechins in wart regression is yet to be identified , but it has been shown to inhibit a broad range of enzymes and kinases involved in the generation of inflammatory mediators . its wide array of biological activities shows great therapeutic potential in treatment of other hpv related tumors ( tyring , 2012 ) . to our knowledge , this is the first report of successful treatment of vin / cis with sinecatechins 15% . prospective studies are warranted to investigate its role in the treatment of vin or other pelvic dysplastic diseases . written informed consent was obtained from the patient for publication of this case report and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal upon request .
highlightsusual - type vin is an hpv - associated premalignant condition that can affect immunocompromised patients and may have multifocal , multicentric involvement.immunocompromised patients who may be poor surgical candidates , and in whom topical modalities may prove ineffective , treatment remains a challenge.we present such a patient in whom sinecatechin was successfully used as an alternative to less desired and effective treatment options .