New Evidence for Genetic Etiology of Vestibulodynia in Women Requiring Vestibulectomy
Terry K. Morgan, MD, PhD1, Martha Monson, MD2, Howard Sharp, MD2, Kristina Allen-Brady, PhD3. 1Departments of Pathology and Obstetrics & Gynecology, Oregon Health & Science University; and the Departments of 2Obstetrics & Gynecology and 3Genetic Epidemiology, University of Utah.
Background: Vestibulodynia is a common multifactorial condition. We and others have reported neurogenic inflammation in the vestibular tissue of these cases, which often has a genetic predisposition (e.g. autoimmune disease and hypersensitivity reactions). Others have also suggested there may be associations between vestibulodynia, atopy, and genetic variants of pro-inflammatory cytokines. Our objective was to test for familial clustering and determine the relative risk for vestibulodynia in relatives using the Utah Population Database (UPDB).
Methods: Retrospective study using the UPDB (2.2 million individuals with at least three generations of ancestry) linked to University of Utah Health Sciences Center CPT (56620, 56625) coded data (1994 present). We also evaluated 216 known primary and secondary vestibulodynia cases treated by vestibulectomy at the University of Utah. We calculated the relative risk (RR) of vestibulectomy in female relatives of affected women and compared the average pairwise relatedness in affected women versus the average UPDB relatedness.
Results: The relative risk of vestibulectomy was significantly elevated in first degree (26.9 [8.7–62.7], p=0.000002), second degree (7.4 [0.9–26.7], p=0.03), and third degree female relatives (5.7 [1.56–14.7], p=0.006). The average pairwise relatedness of affected women was statistically significant to five meiosis (strong evidence for genetic risk). We also identified a number of Utah families with distantly related affected women.
Conclusions: Vestibulodynia likely has many triggers and our data strongly suggest cases requiring vestibulectomy have a genetic predisposition. Future studies will identify specific candidate genes in this population by linkage analysis in affected families and whole genome sequencing of distantly related probands.
Vestibulodynia: Are Pain Ratings Associated With Sexual Functioning?
Leen Aerts, PhD MD1, Sophie Bergeron, PhD1, Myriam Pâquet, BA1, Samir Khalifé, MD2. 1Department of Psychology, Université de Montréal, Montréal, QC, Canada; 2Department of Obstetrics and Gynecology, Jewish General Hospital, Montréal, QC, Canada.
Objectives: Provoked vestibulodynia (PVD) is suspected to be the most frequent cause of vulvodynia in premenopausal women. Gynecological examination with cotton-swab test is suggested to be the standard diagnostic tool to assess this vulvar pain syndrome. The goal of this study was to evaluate the relation between (1) pain during gynecological examination and pain during vaginal intercourse; and (2) pain during vaginal intercourse and psychosexual functioning in a large sample of premenopausal women with PVD.
Methods: A total of 99 women underwent a gynecological examination including cotton-swab test. In addition, participants were asked to rate the pain during friction on the vestibule. Participants completed questionnaires on socio-demographic variables and pain history, a 0–10 pain numerical rating scale (NRS), the McGill-Melzack Pain Questionnaire (MPQ), the Female Sexual Function Index (FSFI), the Global Measure of Sexual Satisfaction (GMSEX), and the State-Trait Anxiety Inventory (STAI).
Results: Pain during the cotton-swab test and pain during vestibular friction were only weakly correlated with pain during vaginal intercourse (r = 0.27 and 0.24, respectively). No associations were found between these pain measures and participants’ state anxiety (r = 0.11 and 0.02, respectively), trait anxiety (r = 0.12 and 0.14, respectively), sexual functioning (r = −0.08 and −0.07, respectively) and sexual satisfaction (r = 0.00 and −0.17, respectively). In addition, there was a lack of concordance between pain during vaginal intercourse and the participants’ state and trait anxiety (r = 0.11 and 0.12, respectively), sexual functioning (r= −0.08) and sexual satisfaction (r= 0.00).
Conclusions: There is a weak association between pain during gynaecological examination and pain during vaginal intercourse. Furthermore, pain during vaginal intercourse is not correlated with sexual functioning and sexual satisfaction. The findings suggest the need to include all of these measures in the clinical evaluation of vulvar pain and in future clinical trials.
Characteristics Of Women With Comorbid Vulvodynia And Bladder Pain Syndrome
Pamela S. Fairchild, MD1, Barbara D. Reed, MD2, Hope K. Haefner, MD1, Mitchell B. Berger, MD PhD1. 1Department of Obstetrics and Gynecology; University of Michigan Health Systems, Ann Arbor, MI; and 2Department of Family Medicine; University of Michigan Health Systems, Ann Arbor, MI.
Objectives: Bladder Pain Syndrome (BPS) is a pain condition associated with vulvodynia, with 1/4-1/2 of women with BPS having concurrent vulvodynia. Our objective is to determine risk factors for co-morbid vulvodynia and BPS.
Methods: This is a secondary analysis of a longitudinal population-based survey study of women in southeast Michigan. Using survey results at a single time point, identifying vulvodynia and BPS with validated screening tools, we used chi-square tests to compare various factors between women without vulvodynia or BPS, those with either vulvodynia or BPS, and women with both. We identified factors associated with comorbid vulvodynia and BPS using ordinal logistic regression.
Results: Of 1864 women, 77% identified as white race, 66.1% were married or in a relationship, 50% had completed college degrees, and 37.9% reported economic hardship. The BPS screen was positive for 141 (7.6%) women, the vulvodynia screen was positive for 150 (8%) of women, and 21 (1.1%) screened positive for both conditions. On chi-square testing, race, educational status, and socioeconomic status were not different between groups. Married (p=0.002) and younger women (p=0.014) were more likely to have both conditions. Childhood symptoms of both disorders and screening positive for irritable bowel syndrome (IBS), fibromyalgia, and depression were significantly different in the three groups, with higher percentages in the groups with vulvodynia and/or BPS (all with p<0.001). On regression analysis, controlling for age and marital status, screening positive for both conditions was associated with IBS, fibromyalgia and menstrual headaches (all with p≤0.017).
Conclusions: Consistent with previous work, women with other chronic pain syndromes (IBS, fibromyalgia) are more likely to have comorbid vulvodynia and BPS. Our data have implications for identifying women with vulvodynia and/or BPS and screening for other pain conditions. Early identification of these women may allow for initiation of multimodal treatment to address the comorbid pain syndromes.
Removal Of The Vestibule For Provoked Vulvodynia: Surgical Experience 1976–2011
Fred H. Ingram, MD. Southern Women’s Health, Flowood, Mississippi.
Objectives: To review the surgical experience of removal of the vulvar vestibule in patients with provoked vulvodynia.
Methods: 210 patients who had surgery from July 1976 to December 2011 for provoked vulvodynia were retrospectively reviewed. All patients were Caucasian except for two that were biracial, and one who was Filipino. The patients had the primary complaint of dyspareunia. The age ranged from 19 to 68 years. The area of discomfort was found to be a foci of redness around the opening of the Bartholin gland ducts and periurethral area. Various oral and topical medicines were used initially and were not successful. Surgery was then used. First a local incision was tried and was successful in three cases. After a few failures a U-shaped incision was developed in 1980 to excise the vestibular tissue. The patients were seen six weeks postoperatively. The duration of symptoms range from four months to eleven years prior to surgery. A follow up of three years was required to be in the study. 10% of the patients had the onset of symptoms with the initial coital experience. Three fourths of these had used oral contraceptives.
Results: Of the 210 patients 20 were lost to follow up. 190 patients were followed for a minimum of three years and 95% are pain free. There were 10 failures (5%). There were 25 patients that had a repeat operation. The operation was done three times on 5 patients and two operations were done on 20 patients. There were 5 failures in the repeat surgery group. 5 patients had post-operative bleeding requiring re-suturing within one hour to forty-eight hours. 10 patients developed Bartholin gland cysts and 8 had surgery for the Bartholin cysts.
Conclusions: Removal of the vulvar vestibule is a very effective treatment for provoked vulvodynia associated with coitus.
Current Practice Patterns For Management Of Vulvodynia In The United States
Vani Dandolu, MD, MPH, MBA, Prathamesh Pathak, B Pharm, MS. Department of Obstetrics & Gynecology, University of Nevada School of Medicine, Las Vegas, NV
Objectives: To evaluate the current practice patterns for the management of vulvodynia in the United States (US) and estimate cost related to this condition.
Methods: Truven Commercial Claims and Encounters Database (CCAE) 2009–2013 were used for analysis. Women ≥18 years with a diagnosis of vulvodynia (625.70) were identified. Study cohort included patients with continuous enrollment for 1 year after diagnosis. Most common diagnostic procedures, most common associated diagnoses and most common prescriptions (by generic name and therapeutic class) were identified and reported for the continuously enrolled patients. Costs were adjusted using medical component of Consumer Price Index (CPI). Statistical Analysis Software (SAS) 9.3 was used for statistical analysis.
Results: Among 24,122 subjects with the diagnosis of vulvodynia, about half (n=12,584) met the enrollment criteria as defined. Mean age was 41.5 yrs +/−12.9. The most common diagnostic procedures were vulvar biopsy (29.6%), and wet smear/potassium hydroxide (KOH)/pH (25.5%). Urinalysis, urine culture, sexually transmitted diseases (STD) testing and yeast culture were also commonly done. Analgesics/ non-steroidal anti-inflammatory drugs (NSAIDs) were the most commonly prescribed medications at 42.7%. Opiates were used in 27.6%. Antibiotics (66.1%) and antifungals (26.1%) were commonly used. CNS agents were also commonly used such as antidepressants (32.4%), anxiolytics/ benzodiazepines (28.6%), anticonvulsants (12.8%) and muscle relaxants (11.3%). Estrogens were prescribed in 15.5% and steroids in 14.6%. The most common local medications used were anti-inflammatory, local anesthetic, and anti-pruritic agents. Others included estrogen creams, steroid creams, and antifungal plus steroid combination creams. About 41.8% had some sort of manual/physical therapy procedures while 12.1% underwent psychotherapy. The mean cost per patient including pharmacy services in the first year after diagnosis of vulvodynia for claims related to this condition was $11,982.50. About 32% had an associated diagnosis of vulvovaginitis, 20.6% had urinary tract infection (UTI), and 15.6% dyspareunia.
Conclusions: There is great variation in the current management of vulvodynia. Besides analgesics, antibiotics, antifungals, antidepressants and other central nervous system (CNS) agents are commonly used. Lack of definite knowledge of etiology and pathophysiology possibly contribute to the variation in practice.
Obesity And Vulvodynia
Christine A. Parker, MS, Hope K. Haefner, MD, Barbara D. Reed, MD. University of Michigan Health System, Ann Arbor, MI, USA.
Objectives: To assess the relationship between obesity, sexual abuse and vulvodynia among women in southeast Michigan.
Methods: Between 2008 and 2013, 2277 women in southeast Michigan participated in the Longitudinal Population-Based Study of Vulvodynia. A telephone survey followed by a 27-page online or written survey, and follow-up surveys assessed health status, medical diagnoses, potential risk factors, and outcomes of screening tests for women with vulvodynia and other medical disorders. Included were women who completed both questions on childhood sexual abuse in the 18-month survey, and on body mass index (BMI) in the 24 month survey. The analysis included frequencies of demographic characteristics, physical and sexual abuse history, BMI, and vulvodynia case status over the course of the study. Associations between obesity and abuse, vulvodynia and abuse, obesity and vulvodynia were determined, and a multivariate model was used to determine if BMI mediates the relationship between abuse and vulvodynia.
Results: Included participants (N=1775) averaged 50 (±2) years, 77% White, 17% Black, 3% Hispanic, and 5% other. 66% were married. 38% found it hard to pay for basic necessities. 33% were obese and 29% were overweight. 19.0% reported sexual abuse before age 18. 21.8% screened positive for vulvodynia over the course of the 6 surveys administered. Despite controlling for demographic variables, both obesity and screening positive for vulvodynia were associated with a history of sexual abuse before age 18 (OR 1.44 (95% CI 1.09, 1.90), and OR 1.90 (95% CI 1.45, 2.49), respectively); however, BMI was not associated with screening positive for vulvodynia, either in the univariate (p=0.891) or the multivariate (p=0.146) analyses.
Conclusions: BMI and vulvodynia status were both associated with demographic variables and history of sexual abuse under age 18. BMI and vulvodynia were not associated with each other, indicating the relationship between abuse and vulvodynia was not influenced by obesity level.
Management Of Vulvodynia And Association With A History Of Yeast Infections: Retrospective Chart Review
Adelaida M. Gyurjyan, BA1, Barbara B. Wilson, MD2. 1School of Medicine, University of Virginia, Charlottesville, VA; 2Department of Dermatology, University of Virginia Health System, Charlottesville, VA.
Objectives: Investigate the relationship between history of recurrent yeast infections and vulvodynia, as well as examine the effectiveness of a novel management protocol.
Methods: We conducted a retrospective chart review of 343 patients presenting with vulvar symptoms to the University of Virginia’s Dermatology clinic within the last five years. The study included only those patients with a diagnosis of generalized or localized-type vulvodynia/vestibulodynia. Patients were prescribed a regimen of Sitz baths, Vaseline, and other basic vulvar care recommendations, including avoidance of irritants and allergens (appendix 1). Oral fluconazole was also prescribed if there was clinical suspicion for occult yeast infection, history of recurrent yeast infections, positive KOH testing, or positive fungal cultures. Treatment efficacy was assessed via subjective patient report at follow-up visits.
Results: Of the 343 patients identified, 62 received a diagnosis of either vulvodynia or vestibulodynia. Of these 62 patients, 33 (53.2%) reported either a current yeast infection or a history of recurrent yeast infections.
Thirty-six (58.1%) of these 62 returned for at least one follow-up visit. All 36 were prescribed at least the basic vulvar care protocol; 23 were also prescribed oral fluconazole. Nineteen of these 23 patients (82.6%) reported at least some improvement on follow-up, with only three (13.0%) reporting no improvement. Of the 13 patients who received only basic vulvar care without fluconazole, eight (61.5%) reported at least some improvement, with five (38.5%) reporting no improvement.
Conclusions: Roughly half of the patients diagnosed with vulvodynia/vestibulodynia reported a history of recurrent yeast infections. When considered along with the background rate of 10-25%, this finding suggests that occult yeast or its inflammatory aftermath may contribute to the development of vulvodynia. Furthermore, this study supports the benefits of basic vulvar care and suggests that fluconazole may be a helpful adjunctive therapy, if occult yeast infection is suspected.
The Prevalence of Gardnerella as a Function of Age: Data from a Provoked Vestibulodynia Cohort
Gloria A Bachmann, MD1, Nancy Phillips, MD1, David Foster, MD2, C Bachour3, L Rawlinson3, J Wan4, PhD3, C Brown, Pharm D3. 1Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 2University of Rochester Medical Center, Rochester, NY, 3University of Tennessee Health Science Center, Memphis, TN, 4Department of Preventive Medicine, University of Tennessee, Memphis, TN.
Objectives: To determine whether Gardnerella was more common in younger as compared to older women with provoked vestibulodynia (PVD), a vulvodynia subtype.
Methods: A culture for Gardnerella was performed in 65 women enrolled in an NIH sponsored clinical trial evaluating the efficacy of gabapentin on their pain management. All women screened for the trial had PVD diagnosed with a gynecologic evaluation and a cotton-swab test. Visual inspection of the vaginal vault and collection of vaginal specimens for wet prep, maturation index and culture were also performed to rule out other etiologies for the vulvar pain symptoms. Gardnerella was confirmed by the VPIII microbial identification test. Data of those positive and those negative for Gardnerella were expressed as mean ±SD and differences between groups in age were analyzed by a two-sample t-test.
Results: Of the sixty-five women studied, 25 women were positive for Gardnerella and 40 were negative. There was no difference in the mean age of those who were positive for Gardnerella (35.16 ±11.71) and those who were negative (37.08 ±14.22) (P = 0.57).
Conclusions: Of interest, over 1/3 of the sample had a positive culture for Gardnerella. Although it was expected that more Gardnerella would be cultured in younger women as compared to the older subjects, this was not the case in this population of chronic pain patients.
LPV In Vitro Model Points To PAMPs and PRRs
Megan L. Falsetta, PhD3, David C. Foster, MD, MPH1, Collynn F. Woeller, PhD3, Stephen J. Pollock, BS3, Adrienne Bonham, MD, MS1, Constantine G. Haidaris, PhD2, Chris J. Stodgell, PhD1, Richard P. Phipps, PhD3. 1Department of Obstetrics and Gynecology 2Department of Microbiology & Immunology; and 3Department of Environmental Medicine, Rochester, NY.
Objectives: We have recently reported the first in vitro model for localized provoked vulvodynia (LPV) and demonstrated that: 1) fibroblast strains obtained from patients at sites of allodynia produce elevated amounts of pain-associated pro-inflammatory mediators (e.g. IL-6, PGE2), and 2) following challenge with pro-inflammatory stimuli (e.g. Candida species and yeast cell wall components), fibroblast production of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) accurately predicts site-specific vulvar mechanical pain thresholds. Our current objective is to better understand the intracellular mechanisms that contribute to LPV pain development.
Methods: We have designed an in vitro fibroblast model system that enables us to challenge patient and age/race-matched control strains with a variety of relevant pro-inflammatory stimuli, including live yeast. Following challenge, we can monitor pro-inflammatory mediator output (correlated to patient pain threshold) in response to selected stimuli and repression of specific pattern recognition receptors (PRRs).
Results: We identified PRRs in vestibular fibroblast strains, including toll-like (TLR) and lectin (e.g. Dectin-1) receptors. For at least some PRRs, the relative protein abundance, at baseline, is significantly elevated in pain-associated strains. When challenged with pathogen associated molecular patterns (PAMPs) of yeast origin, these strains also produce a greater amount of pro-inflammatory mediators compared to strains isolated from “ain-free” areas. Presumably, elevated PRR abundance contributes to mediator release. Furthermore, blockage of individual PRRs reduces, but does not abrogate pro-inflammatory mediator production. Blocking a combination of receptors may be more effective, as inhibitors of the NFkB pathway reduce mediator production to background levels; many of these PRRs signal through NFkB.
Conclusions: Ultimately, vestibular fibroblasts from LPV-afflicted subjects carry an abundant and wide variety of PRRs, suggesting multiple sites of pain induction and numerous potential sites for pharmacologic intervention. These findings are of clinical significance, as they identify new therapeutic targets for a disorder lacking therapies that target the underlying pathology of disease.
Confocal Microscopic Studies Of Regional Matrix Remodeling In LPV And Asymptomatic Genital Tissue
Sarah J. Caveglia, MPH1, David C. Foster, MD, MPH1, Megan L. Falsetta, PhD2, Collynn F. Woeller, PhD2, Stephen J. Pollock, BS2, Adrienne Bonham, MD, MS1, Richard P. Phipps, PhD1,2. 1Department of Obstetrics and Gynecology; 2Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Objectives: We have recently reported the first in vitro model for localized provoked vulvodynia (LPV) and demonstrated that: fibroblasts strains obtained from patients at sites of allodynia produce elevated amounts of pain-associated pro-inflammatory mediators (e.g. IL-6, PGE2). Il-6 exerts a substantial influence on the relative levels of matrix proteins such as elastin and fibrillin. We report on the relative differences of matrix proteins in location-specific whole-mount specimens in the presence and absence of LPV as visualized by confocal microscopy.
Methods: Biopsy samples from two sites: vulvar vestibule and external vulva were taken from LPV cases and age / race-matched controls 40 micron samples were stained for CD90 (Thy1) and CD31, and examined with fluorescent and confocal microscopy. At standard depth from epithelial surface, blinded samples were quantified for elastin and fibrillin.
Results: Through comparative confocal microscopy, as is illustrated in Figure 1, we will show the relative differences in connective tissue components with quantitative analysis of elastin, and fibrillin. The relationship of IL6 and elastin / fibrillin composition will be shown.
Conclusions: These findings are of clinical significance, as they may help to identify an important pathophysiologic element of vulvodynia, explain why surgical excision is effective, and may identify new therapeutic targets for a disorder with limited non-surgical therapies that target the underlying pathology of disease. Regional matrix remodeling may also have ramifications in other conditions such as lichen sclerosus.
Prevalence And Spectrum Of Vulvovaginal Disorders In Mbarara Regional Referral Hospital, Uganda
Edwig Nagabirwa, MD. Department of Dermatology. Mbarara University of Science and Technology.
Objectives: Vulvovaginal disorders are a major cause of distress and morbidity. They can remain asymptomatic yet act as a portal of entry for other sexually transmitted diseases especially human immunodeficiency virus (HIV). A number of women are seen with vulvovaginal disorders in Mbarara Regional referral skin clinic, yet data regarding prevalence and diagnosis are not known. This study aimed at determining the prevalence and spectrum of vulvovaginal disorders seen in Mbarara Regional Referral skin clinic.
Methods: A retrospective data review of medical records of clients who attended the skin clinic in 2014 was systematically analyzed to determine those with vulvovaginal disorders. Data pertaining age, HIV status and clinical diagnosis was obtained and analyzed using the statistical software package STATA 11.Prevalencewas calculated using simple proportion and risk factor for vulvovaginal disorders analyzed univariate logic regression. A P value of < 0.05 was considered significant.
Results: 1605 medical records of females were reviewed; of these 55 (3.4%) presented with vulvovaginal disorders. Genital warts 22 (40.0%), vaginal candidiasis 17 (30.9%), condylomata lata 3 (5.5%), vitiligo 3 (5.5%) and atopic dermatitis 2 (3.6%) were the most common conditions seen. The major risk factor for having vulvovaginal disorders was being HIV positive (p=0.002%, CI 0.3726987 - 0 .6454831). This was more so for genital warts 19 (82%), especially giant condylomata acuminata, as well as crusted scabies (100%).
Conclusions: Vulvovaginal disorders are common and tend to be associated with HIV co-infection. All patients who present with vulvovaginal disorders should be screened for HIV.
Reasons For Non-Attendance In A Vulvovaginal Disease Subspecialty Outpatient Clinic And Implications For Care
Carly Kirshen, MD1, Kari Wanat2, Libby Edwards, MD3. 1Department of Dermatology, Alberta Health Services, Calgary, AB; 2Department of Dermatology, University of Iowa, Iowa City, IA; and 3Carolinas Medical Center, Charlotte, NC.
Objectives: Women with vulvovaginal diseases have been reported to have a significantly reduced quality of life. These patients can have diseases that are challenging to manage and may find difficulty finding a specialized provider. We hypothesized that lack of patient follow-up was secondary to poor improvement, travel involved, cost of care, and frustration with the provider/office. We sought to determine the reasons why patients did not return for follow-up in order to improve management of these diagnoses.
Methods: A retrospective chart review was performed on new vulvar patients seen in the vulvovaginal specialty outpatient clinic by a single private practice dermatologist for chronic vulvar itch or pain from January 1, 2009 through December 31, 2009. If patients did not follow-up as requested, then they were contacted to determine the reason.
Results: Two hundred eighty four vulvar consults were seen in 2009. Seventy-three patients (25.7%) continue to be seen while 111 were eventually discharged from care. One hundred patients total (35.2%) did not follow-up when requested. Of the patients contacted, there were various reasons provided for their failure to return to clinic: condition improved (23%), distance (15%), followed by another physician (8%), financial (8%), felt no more could be done for them (5%), other medical problem (5%), dissatisfied with the clinic (4%), unaware of the need for follow-up (1%). Thirty one percent of those patients could not be reached. A breakdown of missed appointments after initial visit versus follow-up visits will be presented.
Conclusions: Our hypothesis and concern was that vulvovaginal dermatology patients who were not attending appointments were not improving. In fact, our patients were improved, sited distance or cost as an issue, or were managed locally, which contrasts to published results. Continued and improved correspondence locally can help overcome some of the barriers associated with care of vulvar patients.
Homemade Video Lectures Uploaded At YouTube For Free On Line Education In Vulvovaginal Diseases
María M. Domenech, MD. Gynecology Service, Hospital Italiano de Buenos Aires, Argentina.
Objectives: To develop a costless on line education tool for Medical Doctors, students, and patients. YouTube is the biggest and fastest growing video sharing website in the world. One of every two Internet users is in YouTube. It processes 3 billion searches a month. There is scarcity of relevant information related to vulvovaginal diseases in YouTube.
Methods: Very simple video lectures are presented. To make the videos only a pen, paper and a Smartphone are needed. The videos are uploaded to the presenter`s YouTube account and shared with her contacts. The intention is that the lectures are delivered in a simple language, so anyone, not only doctors can understand them. Also great effort is made to share the most up to date information using ISSVD terminology.
Results: There are videos being viewed currently, with an average of 200 visits per month. YouTube offers free Analytics Software that allows registered users to identify the precedence and characteristics of the population that watches the videos. It also allows comments from watchers. People can share the links of the videos in the social networks, blogs or e-mail. It is also a tool to help patients to better understand their conditions.
Conclusions: Internet is widely used for learning and for sharing all kinds of knowledge. YouTube is widely used by many doctors, students and patients. This modality has high potential to grow since the links can be inserted in web pages for educational purposes. It has no costs. The impact and the number of viewers could be greater than some live lectures and visits to web sites related to the specialty.
Vulvar Intraepithelial Neoplasia
Alopecia Of The Mons Pubis
Miriam Keltz Pomeranz, MD, Ronald O. Perelman Department of Dermatology, New York University, New York City, NY.
Objectives: to describe a pattern of alopecia
Methods: Case series; photographs and clinical information on 3 patients with similar patterns of hair loss; review of the literature on hair disease that affects pubic hair.
Results: There are several diseases that may cause hair loss on the mons pubis including alopecia areata, lichen planus (Graham-Little Piccardi Lassuer syndrome) and trichotillomania. However, there is no reason to suspect these rare diseases in most patients.
Conclusions: Central hair loss on the mons pubis in the absence of clinical disease may be more common than recognized.
Labial Tumors Mimicking Bartholin Cysts - A Case Series
Shailaja Devi Anipindi, MD1, Namuduri Rama Padmavathi, MD2, KL Yam, MD2, Chew Sung Hock, MD3. 1Department of general Obstetrics & Gynecology- KK Women’s and Children’s Hospital, Singapore; 2Department of Gynaecological Oncology- KK Women’s and Children’s Hospital, Singapore; and 3Department of Pathology - KK Women’s and Children’s Hospital, Singapore.
Objectives: To present a series of vulvar smooth muscle tumors that clinically mimicked Bartholin cysts. To emphasize some salient features from history and clinical examination for accurate diagnosis of Bartholin cysts.
Case1 - A 44 year old woman presented to the clinic with a 6 month history of painless swelling on her vulva. She felt that the swelling was slowly increasing in size.
On examination a 3.0 x 3.0 cm right labial swelling with signs of inflammation was found. A diagnosis of a Bartholin abscess was made and she was initially treated with antibiotics.
There was no change in size of the swelling after antibiotic treatment. Further evaluation showed that the swelling was on the posterior hub of the right labium majus mimicking a Bartholin cyst, but the right labium minus was not everted.
It was excised and found to contain smooth muscle cells on histopathology. On further immunochemistry it was a leiomyoma.
Case 2- A 71 year old postmenopausal woman presented with a 4.0 x 4.0 cm vulvar mass which was mimicking a Bartholin cyst. It was excised and found to be a myofibroblastoma on histopathology.
Case3- A 55year old premenopausal woman with vulvar swelling in the region of Bartholin gland was found to be an angiomyofibroblastoma on histopathology.
Conclusions: The clinical diagnosis of Bartholin cysts may be mimicked by vulvar masses including smooth muscle tumors. The true histopathological diagnosis may not be found until surgical excision. Histopathological confirmation of diagnosis and close follow up for recurrences are mandatory.
Fournier’s Gangrene. Three Cases
Karina Ayala, MD. Clinica Zacatenco, Mexico D.F.
Fournier’s gangrene is a fulminant necrotizing fasciitis of progressive polymicrobial origin that may affect the external genitalia, including the perianal region. Often patients with Fournier’s gangrene have an associated disease that compromises their immunity, which may result in this serious infection. These include alcoholism, diabetes, advanced age, radiation therapy, liver cirrhosis, neoplasms, phimosis, perineal abscess, or surgery in the genital area. Aerobic organisms are found in 10% of cases; anaerobic organisms in 20%, and 70% consist of mixed flora (aerobic and anaerobic).
Objectives: To present three cases of Fournier’s gangrene to expand our theoretical and practical knowledge base, emphasizing that timely diagnosis and proper treatment improve patient outcomes.
Methods: Three patients ( average age of 60 years) were diagnosed with Fournier’s gangrene and treated in Clinica Zacatenco, Mexico.
Results: The three patients had a significant past medical histories, in particular, diabetes mellitus. All were treated with a triple antibiotic regimen, as well as surgical debridement. The average hospital stay was 20 days.
Conclusions: Fournier’s gangrene is an entity that can be lethal. Early diagnosis and an early aggressive multidisciplinary intervention are essential for proper recovery.
Diagnosis Of Vulvovaginal Candidiasis (VVC): Sensitivity And Specificity Of Nucleic Acid Amplification Testing (NAAT) In Comparison To Candida Culture And Wet Mount
Claire S. Danby, MD1, Lorna K. Rabe, BS2, Sara M. Hendrickson, BS2, Andrew D. Althouse, PhD2, Sharon L. Hillier, PhD1,2, Harold C. Wiesenfeld, MD, CM1. 1Department Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital of the University of Pittsburgh Medical Center; and the 2Magee-Womens Research Institute, Pittsburgh, PA.
Objectives: Nucleic acid amplification testing (NAAT) is commercially available for the diagnosis of vaginitis. We hypothesized that NAAT would perform better than culture for the diagnosis of vulvovaginal candidiasis (VVC) among symptomatic women. Our objective was to compare the sensitivity and specificity of commercial NAAT to vaginal candida culture and wet mount for the diagnosis of VVC.
Methods: 174 nonpregnant women with vulvovaginal symptoms were enrolled. Vaginal swabs were collected for 10% KOH wet mount performed by a single investigator, yeast culture and NAAT for C albicans and C glabrata. VVC was defined by a combination of self-reported pruritus, irritation and/or burning plus a positive culture and/or NAAT. Sensitivity and specificity analyses were performed.
Results: Mean age was 34 years (range 18–65), 49% Caucasian and 46% African American. 29% smoked, 16% douched and 69% were sexually active. Symptoms consistent with VVC (pruritus, irritation and/or burning) were present in 136/174 (78%) women while 38 had other vulvovaginal symptoms including discharge, odor and/or redness. Culture and/or NAAT confirmed VVC in only 52/136 (38%) of women reporting symptoms consistent with VVC. Culture was moderately less sensitive than NAAT (78.9% vs 94.2%, p-value = 0.092) but detected 2 additional cases of C albicans and 1 case of C tropicalis that were not detected by NAAT.
Conclusions: 62% of women with VVC symptoms do not have Candida, even when NAAT is performed. While NAAT is the most sensitive method for detection of Candida in VVC, culture had higher specificity. Although wet mount is the most widely used method to diagnose VVC, in our study wet mount failed to detect yeast in 58% of VVC cases.
Genital High Grade Squamous Intraepithelial Lesions: Is The Diagnosis Suspected By Dermatology Providers Prior To Biopsy?
Jill I Allbritton, MD, Miraca Life Sciences, Glen Burnie, MD.
Objectives: Clinicians frequently submit genital lesions, thought to be benign diagnoses such as seborrheic keratosis or nevus prior to biopsy, that are diagnosed as high grade squamous intraepithelial lesions (HSIL) on histology. The objective of this study is to determine how frequently clinicians consider HSIL prior to biopsy.
Methods: A retrospective chart review was performed of cases diagnosed as genital HSIL at a National Dermatopathology laboratory between January 1, 2008 through January 1, 2014. Genital was defined as specimens labeled by the clinician as buttock, perianal, vulva, mons, groin, inguinal, upper thigh, pubic, suprapubic and labia. Recurrent cases and previously diagnosed cases were excluded. Since HSIL terminology is a relatively new term advised by the Lower Anogenital Squamous Terminology (LAST) consensus conference, cases were identified with the diagnoses of HSIL, vulvar intraepithelial neoplasia (VIN), Bowen’s disease, Bowenoid papulosis, squamous cell carcinoma in situ and full thickness epithelial dysplasia. The provided clinical information was examined to identify prebiopsy diagnoses.
Results: One hundred and thirty specimens from 127 patients were identified. In 49% of patients there was no documented suspicion of malignancy (HSIL, squamous cell carcinoma (SCC), basal cell carcinoma or melanoma). In patients younger than 50 years, only 37% of the biopsies included a clinical suspicion of HPV or SCC. In contrast, for patients older than 50 years, 51% of the biopsies included a clinical suspicion of HPV or SCC. In 28% of patients, the prebiopsy diagnoses were limited to pigmented lesions.
Conclusions: Dermatology providers often fail to consider the diagnosis of HSIL in pigmented genital lesions. HSIL should be considered in the clinical diagnosis of all pigmented lesions in genital sites.
Differentiated (Simplex) Vulvar Intraepithelial Neoplasia: A Study Of 18 Cases With Analysis Of Phosphohistone-H3 (Phh3), P53 And P16ink4a Studies
Jennifer R. Loch, DO, Michael D. Black, MD, Demaretta S. Rush, MD, Edward J. Wilkinson, MD. Department of Pathology, University of Florida College of Medicine, Gainesville, FL.
Objectives: In 2004 the International Society for the Study of Vulvovaginal Disease (ISSVD) introduced a two-tier classification system for vulvar intraepithelial neoplasia (VIN) to describe intraepithelial squamous neoplastic lesions of the vulva. VIN was classified either as the classic type (VIN) or differentiated (simplex) type (dVIN). Subsequently there has been very little published in the literature to describe differentiated (simplex) VIN. The objective of our study is to review dVIN within our institution, studying both the histopathologic characteristics and immunohistochemical features of these lesions using phosphohistone-H3 (PHH3), p53 and P16INK4a to evaluate the clinical utility of such studies in the diagnosis of dVIN.
Methods: The study received approval from the University of Florida Institutional Review Board. Twenty-six cases identified as differentiated type VIN were retrieved from the pathology files at the University of Florida from 2005 to 2014. Only 18 cases however had sufficient tissue for immunohistochemical analysis of PHH3, p53 and p16INK4a.
Results: Of the 18 cases identified, 14 cases (78%) had associated invasive squamous cell carcinoma and 12 cases (67%) had associated lichen sclerosus. P53 showed supra-basal expression in 16 of the 18 patients (89%). P16INK4a was negative in 15 of the 18 patients (83%). The mitosis-specific marker, PHH3, highlighted between 1 and 60 mitosis per 10 high power fields (HPFs). Increased mitosis was more commonly found within the dVIN lesion as compared to the surrounding benign vulvar tissue within the same block.
Conclusions: The most helpful feature of differentiated (simplex) VIN is to use strict histopathologic criteria. Of the 3 immunohistochemical stains we examined (PHH3, p53, p16), all were useful as complementary tools, but none had 100% specificity for the diagnosis of dVIN. Benign vulvar tissue and lichen sclerosus alone can have reactivity to p53 in some cases, limiting reliability on immunohistochemistry for the diagnosis.
Identification of Suitable Reference for MicroRNA Expression Measurement in Plasma of Patients with Vulvar Squamous Cell Carcinoma and Patients with High Grade Squamous Intraepithelial Lesions
K. Zalewski, MD1,2, M. Misiek, MD1, A. Kowalik, PhD3, J. Kopczynski, MD, PhD4, A. Zielińska, MD, PhD2, M. Bidziński, MD, PhD5,6, J. Radziszewski, MD, PhD7, S. Góźdź, MD, PhD8, M. Kowalewska, PhD9. 1Department of Gynecologic Oncology, Holycross Cancer Center, Kielce, Poland; 2Chair and Department of Obstetrics, Gynecology and Oncology, 2nd Faculty of Medicine, Warsaw Medical University, Poland; 3 Department Molecular Diagnostics, Holycross Cancer Center, Kielce, Poland; 4Department of Pathology, Holycross Cancer Center, Kielce, Poland; 5Faculty of Heath Sciences of the Jan Kochanowski University, Kielce, Poland; 6Inflancka Specialist Hospital, Warsaw, Poland; 7Department of Surgical Oncology, Holy Family Hospital, Warsaw, Poland; 8Department of Clinical Oncology, Hollycross Cancer Center, Kielce, Poland; and 9Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Objectives: To date, no suitable reference microRNA have been identified in plasma of patients with vulvar squamous cell carcinoma (VSCC) and high grade squamous intraepithelial lesions (HSIL) of the vulva for normalizing real-time RT-PCR (qRT-PCR) assays. The purpose of this study was to select appropriate references for microRNA expression studies in plasma of patients with these tumors.
Materials and methods: We analyzed plasma samples obtained from 29 VSCC and 11 HSIL patients. Expression of six microRNAs (hsa-miR-425-5p, hsa-miR-191-5p, hsa-miR-93-5p, hsa-miR-423-5p, hsa-miR-103a-3p, hsa-miR-16-5p) was analyzed by RT-qPCR. The microRNA molecules in question were chosen based on literature data documenting their stable levels in human plasma and served as candidate reference molecules. The expression stability of these genes was assayed using geNorm software application.
Results: The analysis of gene expression data with geNorm identified hsa-miR-423-5p (M=1,0232) as the most stable reference microRNA for VSCC, followed by hsa-miR-93-5p (M=1,0484) and hsa-miR-16-5p (M=1,4166). In HSIL, plasma hsa-miR-93-5p (M=1,5496) was the most stable reference microRNA. The results pointed at hsa-miR-93-5p (M= 1,2544) as the gene that retained the greatest robustness in plasma samples of both VSCC and HSIL patients.
Conclusions: Our work is the first report on reference selection for microRNA profiling in plasma of VSCC and HSIL patients. A ranking of candidate microRNA?stability values for this types of tumors is provided and might serve as a valuable guide for future gene expression studies of these rare entities.
Use Of Gata-3 And Uroplakin-Ii In Differentiating Primary Cutaneous Vulvar Paget Disease From Pagetoid Urothelial Intraepithelial Neoplasia
Kent Newsom, DO, Layla Alizadeh, MD, Samer Z. Al-Quran, MD, Edward J. Wilkinson, MD. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL.
Objectives: Urothelial carcinoma of the bladder secondarily involving vulvar skin, known as pagetoid urothelial intraepithelial neoplasia (PUIN), can be challenging to distinguish from primary cutaneous vulvar Paget disease (PCVP). Since the report of prior studies using Uroplakin-III (UP-III) to distinguish these lesions, two immunohistochemical studies (IHC) for urothelial carcinoma, GATA-3 and Uroplakin-II (UP-II), have been introduced reportedly with better sensitivity and specificity for urothelial carcinoma compared to UP-III. The objective of the study aims to determine whether GATA-3 and UP-II can be used when attempting to differentiate PCVP from PUIN lesions.
Methods: Eighteen cases were identified including three PUIN and fifteen PCVP cases. GATA-3 and UP-II IHC were performed on formalin-fixed paraffin-embedded tissue. GATA and UP-II IHC immunoreactivity in tumor cells was qualitatively scored (0-3+) by three pathologists who were blinded to the original diagnoses. Previously performed UP-III IHC was also reviewed.
Results: All (3/3) PUIN cases were immunoreactive for UP-II and showed intense (3+) or focal moderate (2+) tumor cell positivity. None (0/15) of the PCVP cases were immunoreactive for UP-II. Review of UP-III IHC on PUIN cases demonstrated one case without immunoreactivity and two with focal faint positivity within cutaneous urothelial tumor cells. GATA-3 was positive in tumor cells and normal epidermis in all cases.
Conclusions: UP-II IHC has value in differentiating between PCVP and PUIN, demonstrating greater sensitivity than UP-III and greater specificity than GATA-3. We found 100% sensitivity and 100% specificity for UP-II staining of PUIN (3/3) and 100% negative staining within PCVP (0/15). GATA-3 was not useful in differentiating PCVP from PUIN. UP-II has utility as an initial screening antibody and as part of an IHC panel in the work-up of vulvar Paget disease, showing improved sensitivity and overall staining intensity when compared to UP-III.
Vulvar Paget Disease: A Single Centre Experience On Medical Treatment With Imiquimod Cream 5%
Eleonora P. Preti, MD1, M. Preti, MD1, N. Spolti, MD1, L. Spinaci, MD1, F. Sanvito, MD1, M. Bertolino, MD2, Mario Sideri, MD1. 1Unit of Preventive Gynecology, European Institute of Oncology,Milan, Italy; and 2 Department of Obstetrics and Gynecology, Hospital SS Pietro e Paolo, Borgosesia (VC), Italy.
Objectives: To evaluate the efficacy and safety of treatment with Imiquimod cream 5% (3M, St. Paul, MN, USA) on patients with vulvar Paget Disease (VPD).
Methods: 37 patients with VPD, referred to the European Institute of Oncology from August 1999 to May 2013, were treated with Imiquimod cream 5% (3M, St. Paul, MN, USA ). Reduction of clinical extension of the lesion and relief of symptoms were evaluated. Imiquimod was applied from once to 3 times weekly for a period ranging from 6 up to 24 weeks. Long-term maintenance therapy was also considered
Results: 11% of patients had a complete remission of lesion and symptoms, 51% partial regression of lesions, 16% had stable disease, 11% had only subjective response, 7% of patients had a progression to invasive disease. 8% of patients stopped the treatment for side effects.
Conclusions: Imiquimod cream 5% (3M, St. Paul, MN, USA) seems to be effective in treatment of VPD. Larger multicenter prospective studies are needed to further validate this treatment particularly in extensive and recurrent cases.
Primary Extra Mammary Paget Disease Of The Vulva (EMPDV): 20 Years Single Institute Experience
Eva Myriokefalitaki, MD, Vishanthi Shesha, MRCOG, Kriti Singhania, Esther L. Moss, PhD, Quentin Davies, FRCOG. University Hospitals of Leicester, Leicester, UK.
Objectives: Extra mammary Paget disease of vulva (EMPDV) is a very rare genital neoplasia associated with a high frequency of local recurrences. The aim of this study was to identify the clinicopathologic features and treatment outcomes of EMPDV.
Methods: This is a retrospective study of all patients with EMPDV over a 20 year period (01/10/1994 – 31/12/2014). We identified 18 patients that were biopsy proven, who were diagnosed and managed in a tertiary University hospital.
Results: The mean age of patients was 74 years (range = 48–93 years) and 89% were Caucasian. All of them were post menopausal and 58% of them suffered from a connective tissue diseases (rheumatoid arthritis, polymyalgia, and osteoarthritis). Symptoms at presentation included irritation, soreness and redness. Lesions were 30% erythematous, 23% hyperkeratotic, 23% had leukoplakia and 15% ulcerative lesions. 71% were >2 cm in size and 64% were identified on the labia. Surgical excision was the primary treatment in 82% of cases and in 67% of cases, margins were involved. Local corticosteroids had been used intermittently in 43% of patients. Median follow-up was 57.5 months (range = 6–276). Local recurrence occurred in 9 patients (50%), and 4 (22.2%) developed invasive EMPDV. All these patients required further surgical treatment. Median time to recurrence was 11 (range 6–156) months. 5 (27.8%) experienced more than one recurrence. EMPDV was not a direct cause of death in any of these cases.
Conclusions: Although recurrence rate of EMPDV was high, invasive disease diagnosis was low. Therefore conservative management would be acceptable. Long-term follow up is necessary for improvement of symptoms and prognosis.
Improving Patient Outcomes In Vulvar Melanoma
MC Macdonald1, N Curry2, JA Tidy3, J Palmer3. 1Subspecialty trainee Gynaecological Oncology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield. UK; 2Specialty trainee, Barnsley District General Hospital, South Yorkshire, UK; and 3Consultant Gynaecological Oncologist, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield. UK. 3
Objectives: Vulvar melanoma is rare. This is reflected by a paucity of data in the literature, low volumes of cases reported per institution and the absence of standardized management guidelines.
Methods: A retrospective cohort study was performed from January 2004 to December 2014. Case notes and histopathology reports were cross-referenced with data from the pathology database.
Results: During the time period thirteen cases of vulvar melanoma were registered with the gynecological oncology service at our center. Median age at diagnosis was 61 years. The majority presented with a vulvar lesion (44%). Management and outcomes; two women referred for best supportive care died within one month of presentation, ten underwent wide local excision of the primary tumour, three had palliative chemotherapy, one of these patients also had palliative radiotherapy. One woman was treated with palliative radiotherapy alone. Median survival time was 21.8 months; two women remain alive at 32 and 98 months. Overall five year survival was 18%.
Conclusions: Our data agree with previously published data on the poor prognosis of vulvar melanoma. The British Melanoma Guidelines make no reference as to who should manage genital tract melanoma. Without doubt, women diagnosed with vulvar melanoma should be managed by multi-disciplinary teams but, as radical surgery is not recommended, the role of the gynecological oncology service is limited and these women would be best managed by specialized melanoma teams.
We propose however that due to its rarity and poor prognosis, vulvar melanoma should be managed in national centers, with centralized registration to increase caseload, improve and unify management, enable prospective trials, and increase specialist knowledge.
Quantitative Molecular Imaging Of Microscopic Pigment Chemistry In Female Genital Tract Melanocytic Lesions Using Pump-Probe Laser Microscopy
Francisco E. Robles, PhD1, S. Deb, PhD1, W.S. Warren, PhD1, M.A. Selim, MD2. 1Department of Chemistry, Duke University, Durham, NC; and 2Department of Pathology, Duke University Medical Center, Durham, NC.
Objectives: We report on the application of a novel molecular imaging technique, pump-probe microscopy, to analyze melanin chemistry in pigmented lesions of the female genital tract.
Methods: Histopathologic specimens of thirty-five previously excised female genitalia tract melanocytic lesions (15 melanomas, 10 melanocytic nevi, and 10 melanocytic macules) were analyzed with pump-probe microscopy. The technique uses a laserscanning microscope with a two-color pulsed laser source to identify chemical differences in melanins based on differences in transient excited state and ground state photodynamics. The pump-probe signatures from unstained sections of the pigmented lesions were correlated with adjacent hematoxylin and eosin (H&E)-stained sections.
Results: We find significant qualitative and quantitative differences between melanin type and structure in tissue regions with invasive melanoma, melanoma in-situ and nonmalignant melanocytic proliferations (e.g., nevi, melanocytic macules). The molecular images of non-malignant lesion have a well-organized structure, with relatively homogenous pigment chemistry, most often consistent with that of eumelanin with large aggregate size or void of metals, such as iron. On the other hand, pigment type and structure observed in melanomas in-situ and invasive melanomas is typically much more heterogeneous, with larger contributions from pheomelanin, melanins with larger metal content, and/or melanins with smaller aggregate size. Differentiation between normal pigmented tissue and melanotic macules is not possible based on pigment type alone. Of significance, clear differences can be observed between melanocytic macules and vulvar melanoma in-situ, which in some cases can be difficult to clinically distinguish.
Conclusions: Pump-probe laser microscopy shows promise as an adjuvant diagnostic tool for evaluating female genital tract melanomas based on morphologic correlation with the histopathology results and pigment chemistry. This initial study suggests systematic chemical and morphological differences in melanin pigmentation among invasive melanoma, melanoma in-situ and non-malignant melanocytic lesions.
Histological Variations By Site In The Normal Vulva
Sean M. Holland, MBBS1, Tania Day, FRANZCOG2, James Scurry, FRCPA3. 1Department of Maternity and Gynaecology, John Hunter Hospital, Newcastle, Australia; 2Department of Maternity and Gynaecology, John Hunter Hospital, Newcastle, Australia; and 3Department of Anatomical Pathology, Pathology North, Hunter New England, Newcastle, Australia.
Objectives: We aimed to define the normal histological features of the vulvar epithelium.
Methods: Vulvar specimens containing asymptomatic perilesional epithelium were identified by reviewing histopathology reports and requisition notes. We assessed stratum corneum morphology as basket weave, compact, or intermediate. The cell layer number within the stratum granulosum was assessed, as was the epithelial thickness (mm). The dermal lymphocytic infiltrate was defined as nil, sparse, moderate, or dense, and was assessed for presence of papillary dermal fibrosis. Descriptive statistics and a summary of the features of each site and epithelial subtype were recorded.
Results: Of 113 cases that met inclusion criteria, 95 were from labia and vestibule, 7 from mons, and 11 from perineum. The labia and vestibule specimens consisted of hair-bearing skin in 40, hairless skin in 39, and squamous mucosa in 16. The stratum corneum was basket weave at the mons, and either compact or intermediate at the perineum. On labial hair-bearing and hairless skin, all three stratum corneum morphologies were observed. Median epithelial thickness was 0.16 +/− 0.09mm and the median granular cell layer number was 3 +/− 1.3. Eleven cases demonstrated parakeratosis which was present at one end of hairless skin in five cases and at the edge of squamous mucosa in six. Scant dermal lymphocytic infiltration was present in most samples; no case demonstrated papillary dermal fibrosis or dense lymphocytic infiltration.
Conclusions: The normal stratum corneum is basket weave on the mons and compact or intermediate on the perineum. All 3 morphologies are observed on the labia. A transition zone of parakeratosis between squamous mucosa and hairless skin is a normal finding. Pathologists need to be aware of site related differences in normal histology to avoid over-diagnosis of disease.
Gynecological Complications Of Allogeneic Hematopoietic Stem Cell Transplantation: A Survey By Self-Assessment Questionnaire In 105 Women
Sandra Ly, MD1, Laure Nazarre, MD2, Stephane Vigouroux, MD3, Reza Tabrizi, MD3, Noel Milpied, MD, PhD3, Marie Beylot-Barry, MD, PhD1. 1Department of Dermatology, University of Bordeaux; 2Department of Gynaecology, University of Bordeaux; 3Department of Haematology, University of Bordeaux.
Objectives: To determine the incidence of allogeneic hematopoietic stem cell transplantation (HSCT) gynecological complications, to describe them and to assess patients’ level of information about them.
Methods: We conducted a monocentric retrospective cross-sectional study in allogeneic HSCT females. A study specific self-administered questionnaire was mailed to all survivors. Questions concern demographic data, vulvar and vaginal symptoms, menopausal status, fertility, sexuality, pre and post-transplant gynecological monitoring and information received about HSCT gynecological complications.
Results: Out of 105 females transplanted from April 2007 to October 2012, 89 completed the questionnaire. The median age was 51 years (19–64). The median range from allogeneic HSCT to questionnaire assessment was 30 months. 81% of patients experienced vulvar and vaginal symptoms (dryness, dyspareunia, loss of vaginal elasticity). No correlation with GvHD was found. All of the 47 non-menopausal women before transplant developed a post-transplant amenorrhea. Only 34% received hormonal replacement therapy whereas 71% had climacteric symptoms. Regarding infertility, 17% of cases were referred for specialist advice. Absence of sexual activity (57%) was related to absence of partner (31%) or desire (46%), to physical impairment (33%) or asthenia (16%). Sexually active women experienced a decrease in sexual activity and in sexual pleasure, respectively less 70% and 50% post-HSCT. Sexual dysfunction impacts on quality of life (QOL) in 85%. Before the allogeneic HSCT and during the follow-up, 74% of patients received information about ovarian failure and only 30% about genital GvHD, sexual dysfunction and cervical dysplasia.
Conclusions: Allogeneic HSCT gynecological complications are very common and mostly related to an ovarian failure, and not directly to GvHD in our study. The high response rate (85%) emphasizes the need for information and support from patients. A backgrounder has since been created with the patients’ collaboration and a clinical network of specialists (hematologists, gynecologists and dermatologists) implemented for the women, pre- and post-transplantation.
Vulvovaginal Graft-Versus-Host Disease: A Case Series In A Tertiary Referral Centre In Auckland, New Zealand
Cindy Ooi, FRANZCOG1, DM, Rowan, FACD2. 1Obstetrician and Gynaecologist, Department of Obstetrics and Gynaecology, National Women’s Hospital, Auckland, New Zealand; and 2Dermatologist, Vulva Clinic, National Women’s Hospital, Auckland, New Zealand.
Objectives: Female genital tract graft-versus-host disease (GVHD) is a common, yet under-reported complication of allogeneic stem cell transplant. The lack of local experience poses a challenge in identifying and managing these women. We present a case series of four women with genital tract GVHD to highlight the clinical presentations of this condition. It will highlight a gap in service provision for women with this condition, in a tertiary referral hospital in Auckland, New Zealand.
Methods: A retrospective search was performed on patients referred to the Vulval Clinic in National Women’s Hospital, Auckland, New Zealand for vulvovaginal GVHD from 2000–2014. The medical records of eligible patients were reviewed. A literature search was performed.
Results: Four women were identified. Their ages ranged from 40 to 58 years. Two women received unrelated donor stem cell transplant. One received a sibling bone marrow transplant and one received a sibling stem cell transplant. The time of presentation ranged from 1 to 5 months post-transplant. All of them had involvement of other organ GVHD, including liver, skin and oral cavity. The severity of their disease ranged from mild to severe. Two women with mild and moderate disease improved with topical vaginal steroids. The other woman with mild disease did not require any treatment. The woman with severe disease had complete vaginal stenosis at 15 months post-transplant despite treatment.
Conclusions: This case series highlights the under-reporting of women with genital tract GVHD. It is our intention to set up collaboration with our hematology colleagues to address this, given that vulvovaginal GVHD can have significant impact on quality of life.
Clinical Considerations for Pre-Pubertal Lichen Sclerosus
Zahi Ben-Aroya, MD, Libby Edwards, MD. Southeast Vulvar Clinic, Charlotte, NC.
Objectives: Assess the unique characteristics of prepubertal lichen-sclerosus.
Methods: Study population were 33 prepubertal patients with LS, followed at our clinic between 2001–2014. Patients completed a questionnaire assessing clinical, physical and medical data. Patients were treated according to mainstays of therapy with daily superpotent corticosteroids.
Results: Average follow-up time: 10.4±3.6 years. Mean age at diagnosis: 7.6±2.5 years. Mean age at onset of symptoms: 5.8±2.6 years. Average delay in diagnosis: 21±19 months. Common complaints were itching, hypopigmentation, pain/discomfort, redness and skin fragility (72.7%, 30.3%, 30.3%, 21.2%, 15.2%). 51.5% of patients were diagnosed with LS prior their arrival. None were treated acording to mainstays therapy. Most common findings were hypopigmentation, aglutination of labia minora and clitorial area, purpura, shiny or crinkled skin, edema of clitorial hood, fissures and erythema (94%, 48.5%, 42.4%, 33.3%, 27,2%, 27.2%, 24.2%). Good control of LS was achieved after 5 months of therapy in the majority of patients (78.8%). 48.5% of patients became free from disease after 20 months. 10 Patients (30%) had flares of disease during follow up, 9 after changing to maintenance regimens, of them two patients were considered as poor complience. 7 patients went through puberty/menarche during the follow up period. Among them, 5 patients, with fully controlled LS stopped taking medications and remained free of disease. In 3 children reversal of clitoral phimosis was noted. 2 patients remained with active disease after menarche.
Conclusions: LS in pediatric patients have different charachteristics than adults, probably contributing to delaying the diagnosis. For most patients, the treatment regiments were not used correctly, probably contributing to delay in treatment. With proper treatment, majority of patients showed rapid and marked improvement. For patients with controlled disease during menarche, a period with no treatment and careful observation is a reasonable advice. Patient and physician education programs should be implemented.
Pre-Pubertal Onset Of Vulvar Lichen Sclerosus: The Importance Of Maintenance Therapy In Long-Term Outcomes
Andrew Lee, MBBS1, 2, E Ellis, MBBS3, G Fischer, MBBS (Hons) MD FACD1,2. 1Department of Dermatology Royal North Shore Hospital, St Leonards, NSW, Australia; 2Northern Clinical School, University of Sydney, NSW, Australia; and 3Department of Dermatology, Royal Adelaide Hospital, Adelaide, SA, Australia.
Objectives: There is sufficient published data on the clinical efficacy of induction treatment with potent topical corticosteroids (TCS) in childhood vulvar lichen sclerosus (VLS), but limited data on appropriate long-term management. The disease has been shown to extend beyond menarche and the repercussions of suboptimal long-term disease control may be devastating and permanent. This single-center retrospective study reviewed the outcomes of long-term treatment using individualized maintenance regimens with regular follow up where the target outcome was to achieve complete objective normality in addition to symptom control.
Methods: Forty-six female patients with pre-pubertal onset VLS were studied retrospectively. Information collected included demographic data, treatment prior to presentation, induction and maintenance treatment, clinical response and compliance with treatment. Photographic records were available for all patients.
Results: Thirty-five patients (76%) had received treatment prior to their first consultation. However disease control had been achieved in only 3 patients who were using daily treatment with potent topical corticosteroids. Twelve children (26%) had architectural change on presentation. All patients achieved initial objective disease suppression with induction treatment using potent TCS. Data on maintenance treatment was divided into compliant and non-compliant patient groups. Of the compliant patients, 31/33 (93.93%) had sustained complete disease remission with no scarring. In comparison, of the non-complaint patients, those applying intermittent or no long-term TCS, 1/13 (8%) achieved complete control on maintenance treatment (p<0.0001), 9/13 (69.23%) experienced disease progression during treatment (p<0.0001), with three patients developing scarring during follow up (p<0.001). Those with established scarring on presentation did not recover with treatment.
Conclusions: Our data support previous studies regarding initial treatment with potent topical corticosteroids but additionally suggests that maintenance treatment with individualized regimens that achieve objective normality in addition to symptom control provide optimal outcomes of symptom control and preservation of normal vulvar architecture in puberty and beyond.
Vulvar Lichen Sclerosus And Malignant Transformation: A Longitudinal Retrospective Study
Gianluigi Radici, MD1,2, M. Preti, MD1,2, B. Ghiringhello, MD3, O. Di Pumpo, MD1, S. Privitera, MD3, L. Micheletti, MD1. 1Department of Gynaecology and Obstetrics, University of Torino, Torino, Italy; 2Preventive Gynaecology Unit, European Institute of Oncology, Milan, Italy; and 3Pathology Unit, S. Anna Hospital of Torino, Torino, Italy.
Objectives: To assess malignant transformation risk in vulvar lichen sclerosus (VLS).
Methods: Women histologically or clinically diagnosed as having VLS who had a 1-month minimum follow-up were selected. Vulvar neoplasms have been histologically categorized as vulvar intraepithelial neoplasia (VIN), superficially invasive squamous cell carcinoma (SISCC), and frankly invasive squamous cell carcinoma (SCC). Incidence risk, incidence rate and Kaplan-Meier probability of neoplasia occurrence were calculated.
Results: 976 patients were selected. The median (range) age at diagnosis was 60 (8–91) years. The median (range) follow-up was 21 (1–339) months. 34 patients (incident risk: 3.5%) developed neoplasms (8 VIN, 6 SISCC and 20 SCC). The incidence rate was 8.1/1000 person-years. The probability of neoplasia occurrence at 24, 60, 120, 180, 240 and 300 months was 1.2%, 3.0%, 7.1%, 11.0%, 21.6% and 36.8% respectively.
Conclusions: The higher probability of malignant transformation in the long period suggests a careful and lifelong follow-up in all VLS patients.
Lichen Sclerosus And Lichen Planus And Risk For Malignancy – A Registry-Based Study From Finland
P. Halonen, MD1, Maija Jakobsson, MD, PhD1, O. Heikinheimo, MD, PhD,Professor1, A. Riska, MD, PhD1, M. Leinonen, MD, PhD2, M. Gissler, M.Soc.Sci,PhD, Professor3, E. Pukkala, PhD, Professor2. 1Helsinki University Hospital, Department of Obstetrics and Gynecology, University of Helsinki, Finland; 2 Research of the Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; and 3THL National Institute for Health and Welfare, Helsinki, Finland.
Objectives: We studied the risk for malignancies among women with a previous diagnosis of lichen sclerosus (LS, n=12,144) and lichen planus (LP, n=9,030) in 1969–2012.
Methods: The diagnoses were retrieved from the Finnish Hospital Discharge Registry and the cohort was followed through the Finnish Cancer Registry for subsequent cancer diagnoses.
Results: During follow-up period we found 993 and 919 cancers, respectively, which are slightly more than expected on the basis on cancer incidence rates in the Finnish female population. Both LS and LP were associated with increased risk for vulvar cancer (SIR: 2.58, 95% CI: 1.41-4.33 and SIR: 26.8, 95% CI: 22.7-31.1, respectively). The cancers of the vulva were mainly detected during the first five years of follow-up among patients with LS. The extremely high risk for developing vulvar cancer with patients with LP was evident throughout the whole follow-up time. The risk for cancers of the oropharyngeal cavity was increased with patients with LS. The risk for cancer of the cervix in patients with LP was decreased.
Conclusions: Careful gynecological long-term follow-up is advisable with women with LP. Women with diagnosis of LS may also benefit from a more careful assessment of oral mucosal membranes by dentists.
Perianal Lichen Dermatoses: An Audit Of 60 Cases
Tania Day, MD1, James Scurry, FRCPA2. 1Maternity and Gynaecology, John Hunter Hospital, Newcastle, Australia; and 2Anatomical Pathology, Pathology North, Hunter New England, Newcastle, Australia
Objectives: To determine the diagnostic range of lichen dermatoses of the perianus, their extent, and response to treatment.
Methods: We reviewed perianal biopsies submitted to a tertiary referral pathology service between January 2010 and July 2014 interpreted as “lichen” or “lichenoid.” We collected data on demographics, referring specialty, extent of lesion, and response to treatment.
Results: During the study period, 60 perianal biopsies met inclusion criteria. The distribution of diagnoses was lichen sclerosus (LS) in 25/60 (41.7%), lichen simplex chronicus (LSC) in 23/60 (38.3%), lichen planus (LP) in 10/60 (16.7%), and a non-specific lichenoid reaction in 2/60 (3.3%). Eleven of 25 cases of LS (44%) showed superimposed LSC. Of ten LP cases, nine (90%) were hypertrophic and three of these showed pseudoepitheliomatous hyperplasia; none were erosive LP. Compared to patients in the LS and LSC groups, those with LP were more likely to have a localized lesion. Topical steroids were prescribed in 90.6% cases with treatment data available, and 97.7% of treated patients who returned for follow-up were improved or resolved.
Conclusions: We encountered a spectrum of perianal lichen dermatoses, with LS, LP, and LSC all represented. Lichen sclerosus biopsied at the perianus is often lichenified. Hypertrophic LP is a common form of LP at the perianus.
A Survey of Members of the International Society for the Study of Vulvovaginal Disease (ISSVD) Regarding Vulvovaginal Cosmetic Surgeries
Claudia Marchitelli, MD1, Mrs. Debbie Roepe2. 1Gynecology Service, Hospital Italiano de Buenos Aires, Argentina; and 2Executive Director, ISSVD, Waxhaw, NC.
There is a growing demand for vulvovaginal cosmetic surgeries worldwide, with thousands of women estimated to undergo such procedures every year.
An increasing number of practitioners have been offering various types of vulvovaginal procedures so as to enhance appearance or sexual gratification.
Of concern are ethical issues associated with the marketing of these practices.
Objective: To survey members of the ISSVD to assess whether they agree that the ISSVD should state a position regarding vulvovaginal cosmetic surgeries.
Methods: An electronic survey was emailed to all ISSVD members.
Results: A total of 87 out of 326 members responded the survey (26.7%). Over half of the responders (56.3%) were gynecologists, 14.9% dermatologists, 5.7% nurse practitioners, 2.2% pathologists and other specialists account for 9.9%. Most of the responders were female (67.8%) while 27.5% were males; 56.3% were between 40 and 60 years of age.
The majority reported that vulvovaginal cosmetic surgeries are performed in their countries.
Conclusions: To conclude 93.1% believe that the ISSVD should state a position regarding these practices. Most of them, suggest promoting patient education on normal anatomy, providing links of websites with photos of the wide range of normal vulvar appearance. Information about female sexuality was considered necessary and surgeries to enhance sexual satisfaction should be discouraged. Responders also state that risks of cosmetic vulvovaginal surgeries should be discussed with patients.
The statement will help women and caring physicians on the decision to undergo surgery through a given set of standardized information.
Vulvar Alteration and Concerns in Women with a History of Abdominoplasty: A Case Series
Andrea S O’Shea, MD, Diane E. Elas, ARNP, Colleen K. Stockdale, MD, MS. Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Objectives: We describe three women with a history of abdominoplasty who were referred to our Tertiary Care Clinic with vulvar pain and/or lesion. Physical examination revealed elevation of the clitoris on the pubic symphysis with or without retraction of the clitoral hood in each.
Cases: One patient with localized clitorodynia occurring 9 years following panniculectomy was found to have elevation of the clitoral shaft to the pubic symphysis without clitoral hood retraction. She was prescribed gabapentin and was lost to follow-up. The second patient had generalized vulvodynia occurring 18 months following abdominoplasty with physical examination showing elevation of the mons pubis with retraction of the clitoral hood. She was managed with skin protectants and avoidance of contact irritants as well as topiramate with improvement in her symptoms. The third patient was referred for evaluation of a clitoral lesion that was initially noted 4 years following abdominoplasty. On examination, she was found to have elevation of the clitoris with retraction of the clitoral hood, increased vascularity (localized), and prominence of the clitoris consistent with a varicosity. The individual in this case has given written informed consent to publish these case details.
Conclusions: Abdominoplasty can result in anatomic changes to the female pubic region due to elevation of the mons pubis and consequent elevation of the clitoris with or without retraction of the clitoral hood (see attached image 1). While causation cannot be confirmed from this case series, a temporal association of vulvar/clitoral pain and anatomic alterations with or without lesions following abdominoplasty was present in each case. Awareness regarding potential sequelae from anatomic alteration may lead to improved patient counseling and modified surgical techniques to avoid significant elevation of the mons pubis and vulvar commissure.
What Makes Vulvovaginal Disorders Difficult to Manage
Graeme J Dennerstein, MD, FRCOG1, Tristan Harding, MD, MSC2. 1Melbourne University, Australia; and 2Western Health, Victoria Australia.
Objectives: To determine those aspects of vulvovaginal complaints which cause an obstetrician and gynecologist (OBGYN) sufficient difficulty to refer the patient to a colleague with a special interest in vulvovaginal disease.
Methods: 100 randomly selected cases of vulvovaginal disorders referred by an OBGYN to a colleague with a special interest and experience of these disorders have been analyzed with regard to clinical features, investigation, treatment and final diagnoses.
Results: Pain syndromes (including vulvodynia) were the most common presenting symptom (58%), followed by pruritus (41%). Sexual factors were relevant in 68%. 35% had nothing to find on clinical examination. A stained vaginal smear was examined in 95%, a swab was sent for culture at the initial consultation in 68% and biopsy was performed in 28%. The most common diagnoses were vaginismus (30%), Candida albicans infection (27%), estrogen deficiency (25%), arousal disorder (24%), and contact dermatitis (21%). The remaining diagnoses will be presented. 72% had more than one diagnosis. Counselling was the most common treatment (78%) and the sole treatment in 11%. Other treatments will be presented.
Conclusions: Health practitioners working in this area need to be prepared to deal with more than one diagnosis when a woman presents with a vulvovaginal disorder and work on the diagnoses rather than the treatment. Areas of particular difficulty identified include obtaining a sexual history, avoidance of empirical treatment, lowering the threshold to biopsy and the management of menopausal atrophy.
The Prevention of Vulvodynia. An Update and Sexual Aspects
Graeme J Dennerstein, MD, FRCOG. Melbourne University, Australia.
Objectives: To review the literature on prevention of vulvodynia from 2007 to present, with particular reference to empirical treatment and sexual aspects.
Methods: A PubMed search of ’vulvodynia’ of the last 5 years produced 185 publications which were examined with particular reference to 12 publications found when ’prevention’ was added.
Results: No publication addressed prevention as its primary theme. Most articles used ’vulvodynia’ as a diagnosis rather than a symptom, still often referring to it as a "diagnosis of exclusion". Empirical treatment, topical and systemic, continued to be advocated. There was an increase in acknowledgment of sexual factors, with 13 publications primarily focused on this aspect.
Conclusions: As prevention of vulvodynia remains a neglected area of research, a list of preventive strategies will be presented. To prevent females developing this syndrome greater attention to the management of sexual dysfunction is needed as well as the prohibition of the use of topical medication without a laboratory diagnosis. The introduction of the term ’vulvodynia’ and its use as a diagnosis has been a retrograde step in the management of vulvovaginal disorers.
Evidence-Based Subgroups in Vulvodynia
Barbara D. Reed, MD1, Melissa A. Plegue, MA1, Ananda Sen, PhD1,2, David A. Williams, PhD3. 1Department of Family Medicine, University of Michigan Health Systems, Ann Arbor, MI; 2Department of Biostatistics, University of Michigan Health Systems, Ann Arbor, MI; and 3Department of Anesthesia, Medicine, Psychiatry & Psychology, University of Michigan Health Systems, Ann Arbor, MI.
Objectives: Clinically, vulvodynia presents as a heterogeneous condition; yet evidence supporting diagnostic subgroupings based upon pathophysiology, chronicity or treatment response is lacking. We used cluster analytic methods to identify key variables from a variety of vulvar pain characteristics that were used to divide vulvodynia patients into more uniform pain subgroups.
Methods: Included were 393 women who screened positive for vulvodynia during the 5-year population-based longitudinal study of vulvodynia. Characteristics of pain (e.g., location, intensity), presence of comorbid pain conditions, and legacy methods of subgrouping based upon preexisting literature were evaluated by hierarchical cluster analysis. Variables that were well separated across the clustering solution were used to develop a manual subgrouping algorithm. Relationships between clinical data and the suggested subgroupings were assessed.
Results: Clustering identified two important variables: presence or absence of spontaneous pain, and presence of comorbid pain conditions. Participants were cross-classified by these variables into four subgroups. These were similar in age and ethnicity. Women without spontaneous pain or comorbid conditions had more education, and rated their health better than the other three groups. Those with both spontaneous pain and comorbid pain conditions were most likely to screen positive for depression and had the worst vulvar pain and poorest sleep quality. Post traumatic stress disorder (PTSD) and pain after intercourse were more likely in either of the two groups with comorbid pain conditions compared to those without. Subgroups did not differ on whether their pain was primary or secondary, or whether it was localized to the introitus or more generalized.
Conclusions: Cluster analysis suggested two variables separated participants into evidence-based subgroups: provoked-only vs. spontaneous pain, and presence or absence of comorbid pain conditions. Determination of potential predictors of subgroup membership suggests group differences. Utilizing these variables in future studies of vulvodynia pathophysiology, chronicity or treatment response may indicate subgroupings with differing findings.
A Case Series on Vulvar Seborrheic Keratoses with Concomitant High Grade Squamous Intraepithelial Lesions of the Vulva
Rachel van Eersel, MD, Irene van der Avoort, MD, Msc, PhD, Beth Morrel, MD. Department of Obstetrics and Gynaecology, Ikazia Hospital, Rotterdam, The Netherlands.
We present three cases of patients with vulvar seborrheic keratosis and two cases of simultaneous high grade squamous intraepithelial lesions (HSIL) of the vulva. Seborrheic keratoses are benign epithelial lesions and commonly found on the upper extremities, trunk and face of middle-aged adults but relatively uncommon on the genital skin. The pathogenesis of these lesions is still not well understood. Human papilloma virus (HPV) DNA has been detected in some of these lesions and has been suggested to play an etiological role.[1,2,3,4,5] Despite their benign origin and favorable prognosis, seborrheic keratosis lesions have been reported in association with a number of other skin malignancies like basal cell carcinomas and sometimes even melanoma.
Case series: In our case series we present three women between 34 and 49 years old with vulvar lesions. Histopathologic examinations of all three of them show seborrheic keratosis and two women have concomitant HSIL of the vulva and a history of cervical HPV related lesions.
This case series is a starting point for our ongoing research focussing on the type of HPV in these lesions en whether the noted association is likely to be coincidental or causal.
Conclusions: Seborrheic keratosis is mostly a clinical diagnosis; biopsies are not standard procedure. In case of vulvar lesions, histology is helpful to distinguish between vulvar seborrheic keratosis and HSIL of the vulva.
End of Study Efficacy for Vulvovaginal Disease of a Novel 9-valent HPV L1 Virus-like Particle Vaccine in 16–26 year old women
E. Joura, MD1, S. Garland, MD2, A. Giuliano3, O. Bautista4, J. Chen4, E. Moeller4, M. Ritter4, A. Luxembourg4, on behalf of the V503-001 Study Team. 1Medical University of Vienna, Austria; 2University of Melbourne, Australia; and 3Moffitt Cancer Center, Tampa, FL USA; 4. Merck & Co., Inc., Whitehouse Station, NJ, USA.
Objectives: An efficacy and immunogenicity study of an investigational 9-valent HPV (6/11/16/18/31/33/45/52/58) (9vHPV) vaccine was conducted in women 16–26 years of age to demonstrate immunological non-inferiority of HPV 6/11/16/18 response and efficacy against HPV 31/33/4/52/58-related disease. The report presents efficacy against vulva-vaginal disease through end-of-study (i.e. up to month 54).
Methods: 14,204 healthy 16–26 year-old women were enrolled into an international, double-blind efficacy and immunogenicity study of the 9vHPV vaccine. Subjects received 9vHPV vaccine or quadrivalent HPV vaccine (qHPV) as a series of injections at day 1/month 2/month 6. Primary analyses included subjects who were seronegative at day 1 and PCR negative from day 1 through month 7 for the HPV type being analyzed. Gynecological examinations were performed every 6 months, and abnormal areas were biopsied.
Results: 12,021 women were eligible for this analysis. Efficacy against vulvovaginal disease caused by HPV 6/11/16/18 was equal to qHPV vaccine. Efficacy against HPV 31/33/45/52/58-related VIN/VaIN (any grade) in the primary analysis was 94.4% (95% CI: 67.7, 99.7). No case of high grade vulvovaginal disease related to the 5 new types was observed in the 9vHPV vaccine group and 3 cases were observed in the qHPV vaccine group. The number of external genital biopsies related to HPV 31/33/45/52/58 was reduced by 92.3% (95% CI: 72.4-98.7).
Conclusions: The 9vHPV vaccine was highly efficacious in preventing HPV 31/33/45/52/58-related vulvovaginal disease up to month 54. Efficacy against disease caused by HPV 6/11/16/18 was the same as with the quadrivalent HPV vaccine.
Squamous Intraepithelial Lesions of the Vulva: 30 Years of Experience of a Single Center
M Preti, MD1, L Micheletti, MD2, B Ghiringhello, MD3, E Corvetto, MD2, V Frau, MD2, S Privitera, MD3. 1Preventive Gynecology Unit, European Institute of Oncology, Milan, Italy; 2Department of Gynaecology and Obstetrics, University of Torino, Torino, Italy. 3Pathology Unit, S. Anna Hospital of Torino, Torino, Italy.
Objectives: To determine clinico-pathological characteristics and outcome following surgical treatment of a single Institute series of squamous intraepithelial lesions of the vulva.
Methods: 240 cases of squamous intraepithelial lesions of the vulva were diagnosed and followed at the Department of Gynecology and Obstetrics University of Torino, Italy, from 1981 to 2014 were reviewed.
Results: All the 240 patients were Caucasian, mean age was 54 years (range 19–92) with 25% of patients 40 years and 12% 70 years. 25,4% of patients had used tobacco (median 20 cigarettes/day), 19,2% had prior/concomitant cervical and 6,3% vaginal intraepithelial neoplasia. Among 240 lesions of the vulva, 213 (88,7%) were high grade squamous intraepithelial lesions (HSIL) of the vulva (median age 50 yrs) and 27 (11,3%) were differentiated type (dVIN) (median age 71 yrs). 14,8% of dVIN lesion were multifocal vs 26,7% of HSIL. Median largest dimension of lesion was 20 mm (range 2–150 mm). Invasive carcinoma was diagnosed in 16,7% of excised lesions: 19/27 dVIN (70,4%) and 21/213 HSIL (9,8%). The depth of invasion varied from 0,1 to 2 mm (median 0,50 mm). Excisional margins were evaluable in 202 patients: 124 (61,4%) were positive and 78 (38,6%) negative. Median follow up was 29 months (range 6–39). After surgical excision, intraepithelial disease recurred in 25,0% of patients with positive margins and 16,6% with negative margins. Disease free survival was significantly shorter in patients with positive margins (median 11.7 months) than negative margins (median 17.4 months). Four progressed to invasive carcinoma during follow up with a median treatment-to invasion of 40 months (range 11–123).
Conclusions: Surgically treated intraepithelial lesions of the vulva have a high rate of recurrence and low rate of progression. A significant number of patients initially diagnosed with intraepithelial lesions on vulvar biopsy had invasive carcinoma on excisional treatment. Careful long-term surveillance is mandatory.
Malignant Progression of Anal Intraepithelial Neoplasia (AIN) in HIV Negative Women
Tiffany Lee, MD1, Madeleine Macdonald, MD2, Paul Skinner, MD3, John Tidy, MD2, Julia Palmer, MD2. 1University of Sheffield Medical School, Sheffield, UK; 2Department of Obstetrics and Gynaecology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; and 3Department of Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Objectives: AIN is rare with few studies documenting rates of malignant progression to anal cancer, especially in an HIV negative population. This study aims to identify the rate of malignant progression of AIN in a female HIV negative population, and observe the outcomes of current AIN management in a multidisciplinary service.
Methods: A retrospective cohort study with interval analysis between January 1980 and June 2013 was performed at the multidisciplinary Ano-Vulval Clinic, Sheffield, UK.
Results: During the allocated study period 106 women were registered with a diagnosis of AIN; twenty women were excluded from further analysis (16 had anal cancer diagnosed at first visit, and four were HIV positive). Twelve women (14%) developed anal cancer over median follow-up period of 11 years. The overall risk of developing anal cancer in HIV-negative women was approximately 1 in 7. The five-year risk of developing AIN recurrence was 37.3%. The five-year risk of developing anal cancer was 18.6%. Therefore, the overall five-year survival calculated for the women with AIN alone and anal cancer are 98.6% and 100% respectively.
Conclusions: In the past 25 years the incidence of anal cancer has increased by approximately 50% and has been found to be more common in women. Due to the rarity of AIN and lack of specialized AIN services, there is paucity of data in the literature regarding the natural history of AIN. Determining rates of malignant progression of AIN aids in establishing appropriate management guidelines, and assessing the risks and benefits of current management approaches.
Differentiated Vulvar Intraepithelial Neoplasia: What Are Our Criteria and Beliefs?
Jason Reutter, MD1, Ruth A Walters, MD2, M Angelica Selim, MD3. 1Piedmont Pathology Associates, Hickory, NC; 2 Central Dermatology Center, Chapel Hill, NC; and 3Department of Pathology, Duke University, Durham, NC.
Introduction: We sought to recognize the working diagnostic criteria for differentiated vulvar intraepithelial neoplasia (dVIN) amongst expert pathologists in the field. We also attempted to determine the frequency of definitive diagnosis, terminology of equivocal lesions and beliefs on the biological significance of dVIN.
Methods: Respondents included pathologist members of the ISSVD, companion societies and authors of published literature on dVIN. They ranked 26 histologic, 8 ancillary study and 5 clinical findings as “essential,” “nonessential but strongly supports diagnosis,” “possibly supports diagnosis,” “weighs against diagnosis” or “uncertain significance or noncontributory.” Consensus was defined as 75% of responders. They were asked about diagnosing dVIN on partially sampled lesions, terminology of uncertain lesions, frequency of diagnosis of dVIN relative to uncertain lesions and the concept of dVIN as a precursor to an invasive process.
Results: 23 completed the survey (43% gynecological pathology, 30% dermatopathology and 27% other training). Only “basal layer atypia” met consensus (86%) as essential. Consensus criteria for being at least strongly supportive were: “basal layer hyperchromasia,” “presence of basal layer mitoses” and “large keratinocytes with abundant eosinophilic cytoplasm.” Only “block like positivity with p16” and positive HPV specific studies weighed against the diagnosis by consensus. 87% diagnosed dVIN on partially sampled lesions. Squamous cell hyperplasia with atypia was the most frequent terminology for uncertain lesions. 87% felt dVIN is a precursor to invasion.
Conclusions: Only basal layer atypia was considered diagnostically essential by consensus. Additional criteria that strongly support the diagnosis include: changes affecting the basal layer (e.g. presence of hyperchromasia and mitoses) and abundant eosinophilic keratinocytic cytoplasm. There was not a consensus on any ancillary study to confirm the diagnosis. The majority felt comfortable rendering a diagnosis of dVIN in a partially sampled lesion. Most felt that dVIN is a precursor to invasion.
Site-specific Mesenchymal Control of Inflammatory Pain to Yeast Challenge in Vulvodynia Afflicted and Pain-free Women
David C. Foster, MD, MPH1, Megan L. Falsetta, PhD3, Collynn F. Woeller, PhD3, Stephen J. Pollock, BS3, Kunchang Song, MD4, Adrienne Bonham, MD, MS1, Constantine G. Haidaris, PhD2, Chris J. Stodgell, PhD1, Susan P. Messing, MS5, Michael Iadarola, PhD6, Richard P. Phipps, PhD3. 1Department of Obstetrics and Gynecology; 2Department of Microbiology & Immunology; 3Department of Environmental Medicine; 4Department of Pathology& Lab Medicine; 5Department of Biostatistics & Computational Biology; 6University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA, Anesthesiology Research Laboratories, and the Department of Perioperative Medicine, National Institutes of Health, Bethesda.
Objectives: Through a series of preliminary and published studies, we have been testing the premise that the vulvar vestibule of all women possesses a unique, embryologically-defined, inflammatory / immunologic responsiveness and that localized provoked vulvodyna (LPV) pain reflects an extreme example of a natural phenomenon.
Methods: Fibroblast strains were derived from two regions of the lower genital tract of localized provoked vulvodynia (LPV) cases and pain-free controls. Sixteen strains were derived from four cases and four controls, age and race matched, following pre-sampling mechanical pain threshold assessments. Strains were challenged with six separate stimuli: live yeast species (C. albicans, C. glabrata, C. tropicalis, and S. cerevisiae), yeast extract (zymosan), or inactive vehicle. Production of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) were pro-inflammatory response measures.
Results: Highest IL-6 and PGE2 occurred with vestibular strains following C. albicans, C. glabrata, and zymosan challenges, resulting in the ability to significantly predict IL-6 and PGE2 production by genital tract location. Following C. albicans and C. glabrata challenge of all sixteen fibroblast strains, adjusting for dual sampling of subjects, PGE2 and IL-6 production significantly predicted the pre-sampling pain threshold from the genital tract site of sampling. At the same location of pain assessment and fibroblast sampling, in situ immunohistochemical (IHC)(+) fibroblasts for IL-6 and Cox-2 were quantified microscopically. The correlation between IL-6 production and IL-6 IHC(+) was statistically significant yet biological significance is unknown because of the small number of IHC(+) IL-6 fibroblasts identified. A low fibroblast IL-6 IHC(+) count may result from most IL-6 produced by fibroblasts existing in a secreted, extracellular state.
Conclusions: Enhanced, site-specific, innate immune responsiveness to yeast pathogens by fibroblasts may be an early step in LPV pathogenesis. Fibroblast strain testing may offer an attractive/objective marker of LPV pathology in women with vulvodynia of inflammatory origin.
Immune Activation Enhances Epithelial Nerve Growth in Localized Provoked Vulvodynia
Päivi Tommola, MD1, Leila Unkila-Kallio, MD, PhD1, Anders Paetau, MD, PhD2, Seppo Meri, MD, PhD3,4, Jorma Paavonen, MD, PhD1, Eija Kalso, MD, PhD5. 1University of Helsinki and Helsinki University Hospital/Obstetrics & Gynecology, Helsinki, Finland; 2University of Helsinki and Helsinki University Hospital/Department of Pathology, Helsinki, Finland; 3Research Programs Unit, Program of Immunobiology, University of Helsinki; 4Helsinki University Hospital/Department of Bacteriology and Immunology, Haartman Institute, Helsinki, Finland; and 5Pain Clinic, Department of Anaesthesiology, Intensive Care, and Pain Medicine, University of Helsinki and Helsinki University Hospital.
Objective: To study the role of immune activation in the development of altered pain sensation (allodynia) in localized provoked vulvodynia (LPV).
Methods: We obtained vestibular mucosal specimens from 17 patients with severe LPV treated by vestibulectomy, and from 15 controls. We employed antibodies against PGP9.5 and NF2F11 for immunohistochemistry, and evaluated nerve fibers in the mucosal epithelium and in the epithelium of vestibular glands. To describe PGP9.5 positive nerve fibers we calculated fiber counts per mm of the outer surface of the epithelium. NF2F11 positivity was defined as existence or absence. CD20 antigen was used to identify mucosal areas with increased density of B lymphocytes. To describe the overall intensity of B cell inflammation we calculated B cell activation index (BAI). Mann–Whitney U-test and chi square -test were used for statistical analyses.
Results: We found more PGP9.5 positive nerve fibers in patients than in controls (mean 6.90; CI 95% 4.92 – 8.89 vs. 3.29; CI95% 0.96 – 5.62 fibers/mm, p=0.010). The density of PGP9.5 positive fibers in areas with high B cell infiltration was higher in patients with higher BAI (Spearman’s rho 0.514, p=0.035). NF2F11 positive fibers were found in 10 of 17 (58.8%) patients but not in any of the controls (p=0.001). Patients with NF2F11 positive fibers in the epithelium tended to have higher BAI values than the patients without fibers (mean BAI 4.40; CI95% 2.49 – 6.31 vs. 2.47, CI95% 1.47 – 3.48, p=0.062). We found glandular epithelium in 11 patient samples with a mean density of PGP9.5 positive fibers of 14.98/mm. In one control sample the fiber density was 2/mm. NF2F11 fibers were seen in 8 (73%) of 11 patients but not in the controls.
Conclusion: Excessive epithelial nerve growth in LPV is associated with increased B cell inflammation. This supports the fundamental role of inflammation and immune activation in LPV.
10 Things You (and Your Patients) Should Know about Generalized and Localized Vulvodynia, Pain and the Brain
Alisa Pascale, DNP, RN-C, WHNP-BC. Vincent Gynecology, Massachusetts General Hospital, Boston, MA.
Objectives: Exciting advances in neurobiology are proving that a wide spectrum of mind and body interventions can alter the brain in ways thought to improve coping and reduce pain. Pain conditions such as generalized vulvodynia and localized vulvodynia (vestibulodynia) may be caused, influenced and/or magnified by acute and chronic stressors. The objective of this project was to create a fact sheet for women and their providers that would integrate current research about stress, pain and the neuroplasticity of the brain with what we also know about vulvar pain to help inform new and complimentary ways to think about, manage and treat localized and generalized vulvodynia.
Methods: A literature search of Medline was undertaken in the Fall of 2012 and Spring of 2013. In addition, hand searching of reference lists provided additional pertinent references. In all, sixty-three articles were identified for inclusion in the review and subsequent fact sheet.
Results: The theory of allostasis and the related concept of allostatic load attempt to integrate research from biomedical and psychosocial models of the stress response. The concept of allostatic load has been explored in relationship to many other health conditions, including vestibulodynia, but this information may not be easily accessible to patients or their health care providers. Drawing on three different but related conceptual models of the bio, psycho, and social influences on vulvodynia, findings from the many papers reviewed for this project were incorporated into a fact sheet.
Conclusions: Rather than looking at vulvodynia and vestibulodynia as “all in your head” OR “all in your vulva,” its underlying cause may be better understood within the system of mind-brain-body interactions related to genetic and psychosocial risk factors, biological and/or infectious triggers, coping skills, and personality traits that affect how the brain is able to perceive, process and manage pain.
Can Pain Mapping in Vulvodynia Cases Provide Insights into Mechanisms and Management of Pain
Marek Jantos, PhD1, Sherie Johns, RN, RM2, Anna Torres, MD, PhD3, Ewa Baszak-Radomańska, MD, PhD4. 1Marek Jantos, PhD, Behavioural Medicine Institute of Australia, South Australia. Hon. Professor, Medical University of Lublin, Poland; 2Sherie Johns, RN, RM, School of Nursing and Midwifery, University of South Australia; 3Anna Torres, MD, PhD, Department of Human Anatomy, Medical University of Lublin, Poland; and 4Ewa Baszak- Radomańska MD, PhD, Terpa Clinc, Lublin Poland.
Objectives: To review the role of pain mapping in the diagnosis and assessment of vulvodynia from a historical perspective, and from a current analysis of retrospective data involving 82 participants. Pain mapping seeks to localize the origins of pain, assess its severity, characteristics and spatial distribution. An integrated mapping and assessment protocol is introduced (IMAP) to assess pain of muscular and soft tissue origin.
Methods: Based on inclusion criteria the pain scores of 27 vulvodynia patients were compared with those of 17 bladder pain syndrome (BPS) cases and 25 controls. The analysis compared three pain maps; the external genital, internal pelvic and bladder/paraurethral; and nine anatomical regions in the urogenital area.
Results: Pain mapping scores showed significant differences between patients in the two pain syndromes and the asymptomatic controls, but found no significant differences between vulvodynia and PBS patients on the three pain maps and nine anatomical regions.
Pain scores from the two Chronic Urogenital Pain (CUP) subgroups confirmed that pain of pelvic muscle origin is characteristic to chronic pain conditions, and does not represent the normal state. The paraurethral area was shown to be the source of the highest pain scores, when compared with other maps and anatomical regions. Analysis of pre and post intervention pain scores, where intervention focused on normalizing pelvic muscle function, showed statistically significant reduction of pain scores on all three maps and nine anatomical regions, demonstrating the sensitivity of pain mapping, using the IMAP, to intervention-related change.
Conclusions: The findings show that pain mapping is a promising tool in localizing the origins of pain, and providing insight into the role of peripheral pain mechanisms in CUP syndromes like vulvodynia. Pain mapping can assist in the development of evidence-based interventions, and provides an objective means of evaluating their impact.
Treatment Options and Outcomes in Patients with Vulvodynia
Pina Belfiore, MD, Margherita Giunta, MD, Giuseppe Puccio, MD, Maria Elena Fucà, MD. Dipartimento Protezione della salute e Materno Infantile PROSAMI, Azienda Ospedaliera Universitaria Policlinico (AOUP), Università di Palermo. Palermo, Italy.
Objectives: To describe the treatment options used for a cohort of patients with generalized vulvodynia or localized vestibulodynia and to evaluate outcomes within an observation period of 12 months.
Methods: 85 outpatients (average age 31, range 18-69 years), suffering from chronic vulvar pain attending a vulvar clinic, were consecutively enrolled from January 2010 to July 2014. They underwent medical history, vulvar examination, touch swab test and pelvic floor muscle strength test. Diagnoses followed the ISSVD Vulvodynia classification. Pain, burning and dyspareunia were graded on a visual analogue scale (VAS Score 1-10). The choice of treatment was based on clinical, psycho-sexual and cultural assessment of each patient.
The main treatment options were:
Pharmacological therapy (amitriptyline or pregabalin), trans cutaneous electrical nerve stimulation (TENS ), postural gymnastics and psychotherapy.
Based on a 12 months follow up, the treatment outcomes were defined as recovered, improved (more than 60%), stable and worsened.
The results were analyzed considering the time (t) elapsed from onset of symptoms to diagnosis, the type of syndrome (Vulvodynia vs Vestibulodynia) and the treatment options.
Wilcoxon and χ2tests were used for statistical analyses
Results: Of the 85 women, 64 (75%) suffered from Vestibulodynia and 21(25%) from Vulvodynia.
The outcomes of treatment were: 28 (33%) recovered, 22 (26%) improved, 31 (36%) stable and 4 (5%) worsened.
The Time t averaged 25 months (range 3-84) in the group of patients that recovered or improved; it was markedly lower than that for the stable group (49 months (range3-360).
Conclusions: Early diagnosis was the main factor associated with successful therapy.
The most effective treatment options were pharmacological therapy and TENS.
Studies on larger groups, multicenter trials and multivariate analyses are needed to validate these results.
Experimental Pain Sensitivity in Women with Vestibulodynia: A Pilot Study
Laura A. Frey Law, MPT, MS, PhD1, Colleen K. Stockdale, MD, MS2. 1Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City; and Iowa 2Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa.
Objectives: Pain sensitivity in women with vestibulodynia was investigated using two experimental pain assessments outside the vulvar region: intramuscular infusion of an acidic phosphate buffer and pressure pain thresholds (PPTs) of the lower limb.
Methods: Three women with vestibulodynia (all aged 24 years) participated. PPTs of the lower limb (average of four repetitions over the anterior tibialis muscle) were assessed using a hand-held Somedic digital algometer (30 kPa/sec, 1 cm2 tip) at baseline (pre-infusion) and during the intramuscular infusion. The acidic phosphate buffer (pH 5.4) was infused into the anterior tibialis muscle at a rate of 40 ml/hr for 15 min (10 ml total) as this infusion location has a large body of normative pain response data for comparison. Peak local (infusion site) and referred (ankle) pain ratings were assessed verbally, as well as any vulvar pain at the time of the infusion (0 – 10 Borg Scale).
Results: One participant reported resting vulvar pain at the time of the study (2/10 rating). Peak local pain was higher in two of the three subjects (2.5, 4.0, 9.5) than the average pain ratings in 34 healthy age-matched women (21 – 27 years) from our laboratory, mean 3.0/10 (SD 2.2; range 0.5 to 10). Peak referred pain was also higher in the same two subjects (0, 4.25, and 7.5) than the average of the healthy age- and sex-matched controls (mean 1.5; SD 1.8; range 0 – 9.0). Similarly, women with vestibulodynia exhibited greater mechanical pain sensitivity (lower PPT values) than the average of the healthy controls (mean [SD] 246.3 [101.7] kPa in subjects vs 431.3 [109.33] in controls).
Conclusions: Preliminary data suggest women with vestibulodynia may exhibit greater generalized pain sensitivity to noxious stimuli than a general population of women.
Concerns of Women Presenting to a Vulvovaginal Specialty Clinic
Miriam E. Murray1, Colleen K. Stockdale, MD, MS2. 1Carver College of Medicine, University of Iowa, Iowa City, Iowa; and 2Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa.
Objectives: Women with vulvovaginal conditions present with varying concerns which may cause considerable distress. We undertook a study to better understand the concerns of women seeking care from a vulvovaginal specialty clinic.
Methods: A retrospective cohort study of medical records and patient questionnaire regarding concerns of new patients (n=643) seen at a tertiary referral center between January 1, 2006 and December 31, 2011 was performed.
Women were queried on the presence or absence of specific concerns. Concerns addressed were fear of chronic pain, fear of cancer, loss of a previously satisfying sex life, changes in mood, problems in their relationship with their partners, fear of a sexually transmitted infection, and a sense of isolation due to the private nature of the problem.
Results: All diagnoses with n ≥50 patients were included in the analysis and calculations to assess significant associations to patient concerns (Table 1). Patients with multiple diagnoses were included in all pertinent diagnostic groups.
Conclusions: Women present to a vulvovaginal specialty clinic with a myriad of potential concerns whether or not they are revealed during their encounter. Understanding and addressing the concerns that are most common in specific diagnoses will help to provide individualized and appropriate counseling.
Role of Physical Therapy in the Multidisciplinary Approach to Vulvodynia: Preliminary Results.
Fabrizio Bogliatto, MD, PhD, Michela Miletta, MW. Lower Female Genital Tract Unit, ASLTO4, Turin, Italy.
Objectives: In the clinical practice different specialists approach women with vulvar pain, often without an integrated care pathway. Despite classifications that appear to reflect specific disciplines, it is necessary to focus on the causes playing a significant role in pain origin. Recently, musculoskeletal factors have been recognized as contributors of the mechanism of vulvodynia. The objective of this study is to evaluate the role of the physical therapy as a first line treatment (multidisciplinary) in vulvodynia management.
Methods: Between October 2013 to October 2014, 14 women with vulvar pain were referred to the Lower Female Genital Tract Outpatient Service of our hospital. According to International Society for the Study of Vulvovaginal Disease (ISSVD) Vulvodynia 2003 Classification, a diagnosis of provoked vulvodynia was made in all patients. Every woman was submitted to a physical therapy pathway, managed by a trained midwife and composed by manual therapy, pelvic floor exercises and biofeedback. The efficacy of physical therapy was assessed by adopting a visual analogue scale (VAS) score.
Results: After 4 months of treatment, 9 patients reported an improvement in vulvar and sexual pain with good relief (reduction of 2–3 points VAS score). Two patients were lost to follow up. Three patients reported no improvement and underwent advanced multidisciplinary pain management.
Conclusions: Vulvodynia is a complex syndrome associated with sexual dysfunction and worsening of the quality of life. Successful treatment requires an intervention, addressing a broad field of possible pain contributors. According to our preliminary results, physical therapy may play a pivotal role in improving symptoms, as first line treatment. Further investigations and high-quality studies are needed in order to introduce physical therapy as an integral component of the multidisciplinary approach to vulvodynia, according to a standard specific protocol.
The Etiology of Vulvar Pain and Entry Dyspareunia: A Review of 299 Cases
Jennifer Bradford, MD, Gayle Fischer, MD. The Centre for Vulvovaginal Health, Sydney, Australia.
Objectives: Vulvar pain remains a challenging clinical problem. A consecutive series of vulvar pain presentations was retrospectively analysed to identify trends in diagnoses.
Methods: The database of a private tertiary referral vulvar practice was searched for patients managed between 2011–2014, whose sole presentation was vulvar pain, sexual and non-sexual. The private practice setting did not require institutional approval.
Results: 299 patients who fitted the inclusion criteria were identified. Average age at presentation was 47.4 years (17–86). Average duration of pain was 30 months (1–432).
After assessment, the most common primary diagnoses were neuromuscular pain (89, 29.7%), lichen planus (52, 17.3%), chronic vulvovaginal candidiasis (48, 16%) lichen sclerosus (41, 13.7%) and psoriasis (38, 12.7%). Four women (1.3%) were given a primary diagnosis of psychopathology, and three cases of dyspareunia (1.0%) were assessed as being caused by the male sexual partner. Two (0.7%) cases eluded diagnosis. Analysis of the histories revealed the importance of historical triggers to accurate diagnosis, in particular, the role of operations, childbirth and musculo-skeletal injuries.
There were 75 women whose sole complaint was of entry dyspareunia, and 155 other sexually-active women who additionally had unprovoked vulvar pain. Similar distributions of diagnoses were found in these two groups.
Treatments used were specific to the assigned diagnosis. Neuromuscular pain was managed with combinations of physiotherapy and/or oral neural modifying agents. Surgery was never necessary. 57 (19%) patients were lost to follow up. Of the rest, 155 (64%) had complete or substantial improvement in their pain, 71 (29.3%) had partial improvement, and 16 (6.6%) no improvement.
Conclusions: In this cohort, chronic vulvar pain, including entry dyspareunia, was predominantly associated with dermatological diseases with about one third of patients having primary neuromuscular pelvic dysfunction. We found that history and examination which allowed specific diagnoses permitted targeted therapy with a good success rate.
Novel Topical Therapies for the Treatment of Genital Pain
Adrienne Bonham, MD, MS, Sarah Caveglia, MPH, David C. Foster, MD, MPH. Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Objectives: Few placebo controlled, prospective trials exploring the efficacy of topical medications for the treatment of localized provoked vulvodynia (LPV) exist. The purpose of this study is to determine the efficacy of 5 different active topical medications and a placebo cream in treating this condition.
Methods: Topical amitriptyline 2%/baclofen2%, gabapentin 6%, ketoprofen 10%, ketamine 10% and loperamide 5% compounded in CetaphilTM, and CetaphilTM alone used as placebo were used for two weeks in a double blinded fashion such that every subject received all drugs and the placebo over the study course. A one week washout with base alone was performed between each study compound. Subjects on systemic pain medications, gabapentin or tricyclic antidepressants were excluded. Endpoints for the study include changes in pain with tampon insertion, pain with intercourse and daily pain scores.
Results: To date, 9 women have been enrolled in the study. One was dropped due to noncompliance. One drug, ketoprofen, was dropped due to consistent (75%) complaints of moderate to severe burning with use. No statistically significant improvement in pain with tampon test, daily pain scores or pain with intercourse was noted with any of the compounds tested.
Conclusions: To date, there have been few studies to explore the efficacy of topical medications for LPV. This study introduces a novel design by which several drugs could be studied against each other and against placebo with each patient serving as her own control. The initial findings suggest that none of the studied compounds results in clinical improvement and that perhaps the daily treatment of the vestibule with moisturizer alone may prove as beneficial as topical medical therapy. The study is currently ongoing. We expect 16 patients to have completed the study at the time of presentation.
Low-Level-Laser Therapy for the Treatment of Provoked Vestibulodynia- A Randomized, Placebo-Controlled Pilot Trial
Ahinoam Lev-Sagie, MD1, Asia Kopitman2, Amnon Brzezinski, MD1. 1Department of Obstetrics and Gynecology; and 2Department of Physical Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Provoked vestibulodynia (PVD) is a complex disorder that is difficult to treat. Low level laser therapy (LLLT) is an emerging medical technology where non-thermal laser irradiation is directly applied to treat pain.
Objectives: This randomized, placebo controlled, double-blind trial was designed to investigate effectiveness of LLLT for PVD.
Methods: Thirty four patients with PVD participated, 18 received LLLT and 16 received placebo. Treatment duration was twice weekly for 6 weeks.
Clinical response was assessed by multiple outcome measures including patient verbal report, visual analog scale (VAS), cotton swab test, tampon test, variable daily pain measures, and sexual function parameters assessed using a daily 24-hour pain diary, quality-of-life questionnaires including the Brief Pain Inventory (BPI) and Neuropathic Pain Scale (NPS). Patients were followed for one year.
Results: Groups were comparable in regards to demographic and clinical characteristics. Seventy-eight percent of patients reported moderate to complete improvement following LLLT compared with 44% in the placebo group (p=0.042).
Conclusions: We conclude that treatment by LLLT safely and effectively reduced the symptoms of PVD. This effect was only apparent when patient verbal reports where evaluated. Further studies with a larger population and various treatment protocols are warranted.
Initial Experiences of Using ePAQ-Vulva in Clinical Practice
Madeleine Macdonald, MD1, Charlotte Alexander1, Thomas Gray, MD2, Stephen Radley, MD1, Julia Palmer, MD1. 1Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; and 2Sheffield University Medical School, Sheffield, UK.
Objectives: ePAQ-Vulva is an electronic questionnaire to assess symptoms and behaviours in vulvar disease and record relevant demographic information. ePAQ-Vulva has been used at STH since April, 2014. The objective of this study is to assess our initial experiences with the instrument.
Methods: Prospective data collected from women attending the vulvar clinic between April - December 2014 were analyzed using baseline statistics. Data included ePAQ-Vulva voucher issue rates and subsequent completion rates.
Results: 135 of 157 women were issued a voucher. Sixteen eligible women were not issued a voucher; and three were ineligible. 89 completed (six submissions incomplete), but 40 did not utilize the ePAQ-Vulva voucher. From September 2014, a medical student was appointed as a clinical support-worker for ePAQ-Vulva. Overall completion rate pre support-worker was 61% and post was 68%. Completion rates were similar in the age groups 41–50, 51–60, and 61–70 (76%, 79% and 70% respectively). Completion rates in the 71–80 and 81–90 groups were lower at 53% and 18%. Lichen sclerosus was the most common diagnosis on the clinic (62.5%), followed by VIN (13%) and vulvodynia (9%).
Conclusions: Using a support-worker increased uptake of ePAQ-Vulva and should form a permanent role in the clinic. Older women were less likely to complete ePAQ-Vulva, probably due to computer literacy issues. Greater support and alternative options need to be considered for these patients. ePAQ-Vulva allows a large amount of demographic data to be recorded and is useful for evaluating the service provided in the vulvar clinic at Sheffield Teaching Hospitals.
The Development and Production of a Novel Electronic Personal Assessment Questionnaire to Assess Patients with Vulvar Disease: ePAQ Vulva
Madeleine Macdonald, MD1, Charlotte Alexander2, Thomas Gray, MD1, Stephen Radley, MD1, Julia Palmer, MD1. 1Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; and 2Sheffield University Medical School, Sheffield, UK.
Objectives: The development of an electronic Personal Assessment Questionnaire-Vulva (ePAQ Vulva) specifically designed to assess women with vulvar disease.
ePAQ can be completed online - at home or in clinic, prior to specialist consultation facilitating the direction of subsequent consultation and measurement of responses to treatment.
ePAQ-Vulva allows assessment of women with vulval disease across four different domains: pain & discomfort, skin changes, sexual function, and quality of life. Symptom frequency and impact on quality of life is assessed for each of these domains. ePAQ-Vulva also records demographic information and behaviours, as well as medical co-morbidities, which may affect vulvar disease.
Methods: A survey regarding implementation of ePAQ Vulva was completed by 61 women attending a multidisciplinary vulvar clinic in Sheffield, UK.
Multiple drafts of the questionnaire were modified by vulvar clinic specialists and a final electronic version was produced.
Results: An initial literature review revealed that there was no electronic questionnaire in existence to assess women with vulvar disease.
The results of the survey identified that women wanted clinicians to better address their feelings and perceived concerns related to their vulvar condition.
In addition free-text questions allow women to express their beliefs, ideas and expectations regarding their condition.
Conclusions: By using ePAQ-Vulva, the clinician has access to more information on how a woman’s condition is affecting her life, which symptoms are most bothersome, and what their beliefs and expectations about their condition are.
This allows for a more focussed and individualized consultation and enables a quantitative assessment of responses to treatment.
Workup And Diagnosis Of Vulvovaginal Ulcers: An Algorithm And Decision-Support Tool: A Novel Mobile Application
Michael S.M. Lanham, MD1, Lynette J. Margesson, MD2, Hope K. Haefner, MD, Colleen K. Stockdale, MD3, Libby Edwards, MD4. 1Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, MI; 2Department of Obstetrics and Gynecology and Department of Surgery, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; 3Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa; and 4Department of Dermatology, Carolinas Medical Center, Charlotte, North Carolina.
Objectives: To create a mobile application and educational tool to assist clinicians in the evaluation and treatment of vulvar ulcers.
Methods: The authors first agreed upon the need for an algorithm for the evaluation and treatment of vulvar ulcers. This algorithm was deconstructed and incorporated into a mobile application, with input from those involved in creating the algorithm, as well as other potential end users. Care was taken to keep the design user-friendly, to maximize clinical efficiency in finding the data desired, to limit dependence on internet access, and to maintain modular, easily updated code in the case of changes in recommendations or data in the future.
Results: A mobile application was designed successfully, including a glossary with exemplary images for users to review, with all data available after initial download without the need of internet access.
Conclusions: A mobile application was developed for education and guidance in the evaluation and treatment of patients presenting with vulvar ulcers. Creation of a mobile application that does not depend on internet access for its core data may make this application an option in remote areas. The design and core data can then be translated to other platforms.
Diagnosis And Treatment Recommendations For Vulvovaginal Candidiasis: A Decision-Support Tool: A Novel Mobile Application
Michael S.M. Lanham, MD1, Hope K. Haefner, MD1, Jack D. Sobel, MD2, Lynette J. Margesson, MD3, Libby Edwards, MD4, Colleen K. Stockdale, MD5. 1Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, MI; 2Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI; 3Department of Obstetrics and Gynecology and Department of Surgery, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; 4Department of Dermatology, Carolinas Medical Center, Charlotte, North Carolina; and 5Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa.
Objectives: To create a mobile application and educational tool to assist clinicians with diagnostic and treatment recommendations for vulvovaginal candidiasis, with emphasis on recurrent or resistant candidiasis.
Methods: The authors first agreed upon the need for an algorithm for the evaluation and treatment of vulvovaginal candidiasis, including indications for evaluation and treatment of recurrent infection. Antifungal recommendations were delineated. The algorithm and recommendations were deconstructed and incorporated into a mobile application, with input from those involved in creating the algorithm, as well as other potential end users. Care was taken to keep the design user-friendly, to maximize clinical efficiency in finding the data the user desired, and to maintain easily updated code in preparation for changes in the recommendations or data for the future.
Results: A mobile application was designed successfully, including a glossary of educational images and an index of treatment options.
Conclusions: A mobile application was developed for education and guidance in the evaluation and treatment of vulvovaginal candidiasis. Creation of a mobile application that does not depend on internet access for its core data may make this application an option in remote areas. The design and core data can then be translated to other platforms.
Extrafacial/Genital Presentation of Granuloma Faciale: Case Report
Suzanne Dedden, BSc1, Wouter Touwslager, MD2, Irene van der Avoort, MD PhD1,3. 1Catharina Hospital Eindhoven, Department of Gynaecology; 2Catharina Hospital Eindhoven, Department of Dermatology; and 3Ikazia Hospital Rotterdam, Department of Gynaecology.
This case report describes a very rare case of an exclusively extra facial, presentation of granuloma faciale which was first presented on the vulva. Granuloma faciale is a rare, chronic benign skin disorder of unknown origin. It is characterized by one single or multiple brown-red asymptomatic persistent plaques, nodules or papules predominantly in the face.
We report a case on which a woman was referred to the clinic with complaints of stress incontinence. During the surgical procedure when received the tension free obturator tape, two erosion where noticed on the vulva; one periclitoral and one besides the vaginal orifice. Based on the histological findings the diagnosis of an extrafacial, disseminated form of granuloma faciale was made. Upon further investigation by the dermatologist, several other skin lesions, but none of them facial, were found.
The patient was treated with Dapson, which has a bacteriostatic effect on the mycobacterium leprae. The total absence of facial lesions is very rare and has previously only been reported in 7 cases in literature. The question may rise whether the name granuloma faciale is a proper one when the disease can present itself extra facially.
A Case of Vascular-looking Nodule on the Vulva
Ramapadma Namuduri, MD, MRCOG(UK)1, Hui M. Liew, MD2, Lynette C. Low, MD3, Adele P.C. Wong, MD4. 1Department of Gynaecological Oncology, KK Women’s and Children’s Hospital, Singapore; 2Dermatology Service, KK Women’s and Children’s Hospital, Singapore; 3National Skin Centre, Singapore; and 4Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore.
Case History: A 54 year old lady presented with a lump on the vulva, which had gradually increased in size over the last 3 years. She complained of occasional tenderness and pruritus.
Physical Examination: Clinical examination revealed a solitary 1.0 cm vascular-looking nodule on the right labium majus. The differential diagnoses were a superficial capillary hemangioma or a vascular tumour. An excisional skin biopsy was obtained.
Histopathology: There was a dermal circumscribed nodule composed of bundles of oval to spindle cells with eosinophilic granular cytoplasm and fusiform to cigars-shaped nuclei with subtle atypia. Rare normal mitotic figures were noted. Ki67, the proliferative marker disclosed mitotic activity of approximately 20%. No necrosis was seen. These cells were immunopositive for smooth muscle actin (SMA) and vimentin but immunonegative for S100, podoplanin, desmin, estrogen receptor (ER), progesterone receptor (PR), MelanA, human melanoma black (HMB)-45 and cluster designation (CD) 163. These bundles were separated by irregular slit-like thin-walled vascular channels, occasionally occluded by fibrin thrombi. The vascular channels were lined by CD 31 and CD 34 immunopositive endothelial cells.
The overall constellation of features of eosinophilic granular spindle cells and vascular channels with fibrin thrombi are more in keeping with the diagnosis of an angioleiomyoma with granular cell change.
Case Discussion: Angioleiomyoma, a variant of leiomyoma, is a benign smooth muscle neoplasm. Granular changes in leiomyomata are rare and not well recognized. Histologically, these tumors may be confused with granular cell tumors, benign neoplasms of nerve sheath origin. Our survey of the literature revealed one case of a vulvar angioleiomyoma with conventional histological features. Leiomyomata are typically slow-growing, and usually tender with compression. In the vulva, recurrence after excision is very rare and convincing malignant change has never been documented.
In view of the subtle pleomorphism, rare mitotic index and moderate Ki67 staining index in our case, a wider excision for clear margins was subsequently performed.
Angiosarcoma of the Vulva Presenting as a Benign Looking Lesion
Amanda Selk, MD MSc1,2, Matthew Cesari MD, CM3,4. 1Department of Gynecology, Women’s College Hospital, Toronto, Ontario, Canada; 2Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada; 3Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; and 4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Case: A 64 year old female presents with an asymptomatic small white papule on her vulva that she likens to acne. She is initially treated with estrogen. The lesion grows in size over the course of several months and becomes irregular and painful. The patient undergoes a biopsy 5 months after initially presenting for care. The biopsy shows a spindled and epithelioid malignant neoplasm, most consistent with angiosarcoma.
The lesions multiply and the pain increases. The patient undergoes a left hemivulvectomy (5.5 x 1.5 x 1.5 cm) and a bilateral inguinal lymphadenectomy. Pathology shows a multifocal angiosarcoma, extending from superficial to deep dermis, with skin ulceration overlying the largest focus (2.2 cm). There is perineural invasion, extension of disease to within 0.5 mm of multiple resection margins, and metastatic disease (0.8 mm) to one of five left inguinal lymph nodes.
The lesions recur within 3 weeks of surgery and are small painful white papules. MRI of the pelvis and chest CT is suspicious for metastatic disease in an obturator lymph node. Chemotherapy is initiated. The patient has an allergic reaction to Paclitaxel, so she is instead treated with Abraxane (paclitaxel protein-bound) for 22 cycles. Initially, her vulvar lesions disappear and the pain resolves. After several months of treatment, the pain returns and multiple white nodules appear on the vulva. A biopsy confirms recurrent angiosarcoma.
Conclusion: Cutaneous angiosarcoma is an uncommon aggressive tumor that has rarely been reported on the vulva. Early diagnosis can improve outcomes thus liberal use of biopsy is recommended. Biopsies should be done of lesions that are painful, growing, or atypical.
Eccrine Spiradenoma of the Vulva: Case Report and Literature Review
Leopoldo Tinoco, MD1,3, Ángelo Nicolalde, MD2, Sonia Carrillo, MD3, Violeta Tinoco, MD4, Ramiro Tinoco, MD5, Diana Tinoco, MD3, Pablo Avilés, MD6, Paulo Pacheco, MD6. 1Lower Genital Tract Disorders & Colposcopy Department and 2Pathology Department, Oncology Hospital Solón Espinosa Ayala (SOLCA); 3Institute of Gynecology and Mastology (GINECOMAST); 4Department of Obstetrics & Gynecology, General Hospital “Rodríguez Zambrano”, Manta; 5Department of Obstetrics & Gynecology, Ecuadorian Institute of Social Security (IESS); and 6Department of Obstetrics & Gynecology, Pontifical Catholic University of Ecuador (PUCE), Quito-Ecuador.
Introduction: The eccrine spiradenoma was described for the first time by Kersting in 1956. It is a benign tumor of the eccrine glands. It has been described in a total of 15 benign cases and 50 malignant cases.
The eccrine spiradenoma is a benign tumor of the eccrine sudoriparous glands. This tumor is generally 1 cm in diameter. It occurs frequently on the face, neck, legs and arms. We present a case of an eccrine spiradenoma on the mons pubis confirmed by histopathology and immunohistochemistry.
Methods and Materials: A 53 year old woman presented with a 7 year history of a tumor on her right superior mons pubis. The tumor had progressive slow growth and was painful. On physical examination the tumor was 3 cm in diameter. It was gray-blue in color.
Discussion: The majority of patients present with spiradenomas between 15 to 50 years of age. They often present on the head, neck, and trunk. Presentation in the vulvar region is unusual and corresponds to 1% of the benign vulvar neoplasms. Our patient was found to have this tumor occurring on the mons pubis at 53 years of age. It was localized. The majority of these tumors in the location of the mons pubis are malignant. The malignant tumors described by Dabska in 1972 appear after 50 years of age.
Conclusions: These sudoriparous glands tumors are rare. The diagnosis may be suspected clinically, complemented with ultrasonography and confirmed through surgical biopsy or excision with adequate margins.
Aggressive Angiomyxoma of the Vulva: Case Report and Literature Review
Leopoldo Tinoco, MD1,3, Ángelo Nicolalde, MD2, Sonia Carrillo, MD3, Violeta Tinoco, MD4, Ramiro Tinoco, MD5, Diana Tinoco, MD3, Pablo Avilés, MD6, Christian Molina, MD6. 1Lower Genital Tract Disorders & Colposcopy Department, and 2Pathology Department, Oncology Hospital Solón Espinosa Ayala (SOLCA); 3Institute of Gynecology and Mastology (GINECOMAST); 4Department of Gynecology & Obstetrics, General Hospital “Rodríguez Zambrano”, Manta; 5Department of Obstetrics & Gynecology, Ecuadorian Institute of Social Security (IESS); and 6Department of Obstetrics & Gynecology, Pontifical Catholic University of Ecuador (PUCE), Quito-Ecuador.
Introduction: The aggressive angiomyxomas are uncommon, benign tumors of the soft tissue. They occur mainly in the pelvis and perineum between the 3rd and 5th decade of life. They are painless, with variable size and a slow growth pattern.
The aggressive angiomyxoma (AA) is a benign tumor of connective tissue. It is characterized histologically by a predominant myxoid stroma. It is recurrent and its treatment is surgical. We present 3 cases of patients who had surgical resection of aggressive angiomyxoma.
In the images studied for diagnosis, the magnetic resonance imaging (MRI) was more specific than the ultrasound and computerized tomography (CT) scan.
The immunohistochemistry results demonstrated reactivity: desmin, smooth muscle actin, vimentin, CD34 (Cluster of Differentiation), CD44 and negativity for S100 protein (Solubility in a 100%-saturated solution with ammonium sulphate at neutral pH).
Methods and Materials: We present 3 cases of AA occurring in women treated at GINECOMAST Quito-Ecuador, between 2006 to 2014.
Case 1: A 69 year old woman with genital prolapse, presented with a painless tumor on the external genitalia, without any other symptoms. On physical examination a painless tumor was found in the left labium minus (2.2 x 1.3 cm) (Figure 1).
Case 2: A 53 year old woman presented with a 2 year history of urinary symptoms. On physical examination a 6.5 x 4.7 x 3 cm mass was noted on the left labium majus.
Case 3: A 19 year old woman presented with an asymptomatic vulvar tumor. On physical examination an 1.8 cm pedunculated lesion (painless) was noted on the left labium majus.
Conclusion: For the diagnosis of AA, immunohistochemistry is an important finding. Surgery is the recommended treatment. Recurrences do occur; so long term follow-up is required.
Lipschütz Ulcers: Should We Rethink It? An Analysis of 34 Cases
Pedro Vieira-Baptista, MD1, Joana Lima-Silva, MD1, Jorge Beires, PhD1, José Martinez- de-Oliveira, PhD2,3. 1Serviço de Ginecologia e Obstetrícia, Centro Hospitalar de São João, Porto, Portugal; 2Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal; and 3Departamento de Saúde da Criança e da Mulher, Centro Hospitalar Cova da Beira, Covilhã, Portugal.
Objectives: To describe the characteristics of patients with Lipschütz ulcers (LU), its presentation and to evaluate the role of a standard protocol in the etiological diagnosis.
Methods: Retrospective analysis of all cases of diagnosis of LU at our vulvar clinic during a five-year period.
Results: Out of 110 women with vulvar ulcers, 34 (30.9%) had a diagnosis of LU. The mean age was 29.8±15.55 years (10–79 years). Ten (29.4%) were 35 years old or more. The majority of patients had already had their sexual debut (29, 85.3%). Ten patients (29.4%) referred had at least one previous similar episode. Twenty five (73.5%) had non-gynecological symptoms in the week before; the most common were: odynophagia (13, 38.2%), fever (11, 32.3%), myalgia and upper or lower respiratory tract infection (6 each, 17.6%). The ulcers were located most frequently in the vestibule (20, 58.8%) and the labia minora (10, 29.4%), especially on the right side (28, 82.3%). Multiple lesions (22, 64.7%) were more common than a single lesion. The mean time to full healing of the lesions was 15.6±6.20 days. A microbiological probable cause was identified in 10 (29.4%) patients: cytomegalovirus (CMV) (four cases), followed by Mycoplasma pneumonia (3 cases), Epstein-Barr Virus (EBV) (2 cases) and parvovirus B19 (PVB19) (1 case).
Conclusions: LU can be found in women of any age and, most of them, sexually active. Recurrence is not rare and can be found in a third of patients. Almost two thirds had non-gynecological symptoms in the week before presenting with the lesions. Most lesions occur in the vestibule and labia minora, especially on the right side. Viruses seem to be the most frequent etiologic agents, but Mycoplasma pneumoniae serology should be considered. A standard protocol can effectively exclude sexually transmitted diseases and lead to a diagnosis in up to a third of cases.
Does a Diagnosis of Atrophic Vaginitis on a Pap Smear Signify the Presence of Inflammation?
Debra S. Heller, MD1,2, Gerson Weiss, MD1, Sara Bittman, MD1, Laura Goldsmith, Ph.D1. 1Departments of Obstetrics, Gynecology, and Women’s Health, and 2Pathology & Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ.
Objectives: Vaginal atrophy of menopause shows increased parabasal cells on cytology. This may be accompanied by abundant neutrophils. A shift in the maturation index in the absence of significant inflammation is more accurately termed atrophic pattern. The purpose of this study was to determine whether the diagnoses “atrophic vaginitis” or “atrophic pattern” rendered on a Pap smear were reliable indicators of what was present on the slide.
Methods: A retrospective review of Pap smear slides from University Hospital, Newark was performed. Cases that had been diagnosed with either “atrophic vaginitis” or “atrophic pattern” were selected. Exclusion criteria included any additional diagnosis of neoplasia. Slides were re-reviewed and scored based on abundance of neutrophils (0–5, 5–10, or >10 neutrophils/high power (40x) field, with 10 fields per slide reviewed. Data were analyzed by Chi squared analysis.
Results: 100 cases in each category were scored. There was a significant linear trend among the three categories (increasing numbers of neutrophils) and the proportion of subjects with the diagnosis of atrophic vaginitis (p<0.0001).
Conclusions: A diagnosis of “atrophic vaginitis” on a pap smear was reliably associated with increased numbers of neutrophils. A diagnosis of “atrophic pattern” did not reliably delineate what was present on the slide. As the pap diagnosis of atrophic vaginitis does not correlate with clinical symptomatology, a single diagnostic term that does not suggest a disease process would more reliably communicate the cytology findings to clinicians.
Attention to the Atrophic Vagina in Postmenopausal Women with Chronic Vulvovaginal Symptoms
Libby Edwards, MD, Mr. Robert Craig, CNA, Kelsey Roepe, MA. Southeast Vulvar Clinic, Charlotte, North Carolina, USA.
Objectives: To ascertain the proportion of postmenopausal women with chronic symptoms of burning, irritation, itching or dyspareunia presenting to a vulvovaginal referral clinic with unrecognized, undiagnosed, or uncorrected vaginal atrophy.
Methods: This is a retrospective review of 100 charts of postmenopausal women referred for sensations of chronic vulvovaginal burning, irritation, dyspareunia, or itching. The investigators assessed accompanying referral records for attention to estrogen deficiency. They recorded the proportion of patients who received estrogen, and the type and dosing of the estrogen. Patient charts from the initial consultation at the specialty referral clinic were reviewed for the presence of an atrophic vagina by examination and wet mount.
Results: Only 32 of 100 postmenopausal women with chronic vulvovaginal symptoms patients had been prescribed topical or oral estrogen replacement. Of those 32 patients, at the initial consultation at the vulvovaginal referral clinic, 15 had a normal wet mount, and 17 exhibited an atrophic vagina with parabasal cells and no lactobacilli on wet mount. Many of these 17 patients with an atrophic vagina were using their estrogen creams externally, or never filled their medication due to cost or fear of side effects, or reported that they often forgot to use their estrogen. Overall, 54 of 100 of all women had an atrophic vagina or atrophic vaginitis at the initial visit, although this was the sole diagnosis in only 4 women.
Conclusions: Many providers treating postmenopausal women with chronic vulvovaginal burning, pain, dyspareunia, or itching are not attuned to the role that estrogen deficiency might play in the patients’ symptoms. In addition, patients treated with estrogen often do not use this medication in a dosing regimen that corrects an atrophic vagina, so that follow evaluations and, often, wet mounts are indicated to ensure improvement.
Desquamative Inflammatory Vaginitis: Presentation of a Case
Eva C. Johannsen, MD1, Mette Meinert, MD, PhD2, Jane Baumgartner-Nielsen, MD3. 1Department of Gynecology and Obstetrics, Rigshospitalet, University Hospital Copenhagen; 2Department of Gynecology and Obstetrics, University Hospital Aarhus; and 3Department of Dermatology, University Hospital Aarhus.
Objectives: Desquamative inflammatory vaginitis (DIV) is a rare, severe form of chronic vaginitis of unknown etiology.
Methods: A 41 year old, para 2, otherwise healthy patient presented with a 13 year history of vulvovaginal symptoms. Since a vaginal delivery in 2001 complicated by an anal sphincter laceration, profuse vaginal discharge, vulvar irritation and dyspareunia were ongoing symptoms. The patient was examined and treated in several gynecological departments without success. Suggested diagnoses and treatments given without convincing effects including: bacterial vaginosis, atrophic vaginitis, lichen planus, genital herpes and autoimmune disorder affecting the vulva/vagina. Due to the lack of diagnosis the patient was re-examined by an interdisciplinary team of dermatologists and gynecologists at the University Hospital of Aarhus, Denmark.
Results: The clinical examination showed purulent discharge and vaginal erythema. The pH was elevated (>4.5) and microscopy of vaginal secretions revealed an increase in inflammatory and parabasal cells. Vaginal cultures, polymerase chain reaction (PCR) and tests for sexually transmitted diseases were negative. Biopsies from the vulva showed chronic inflammation (no plasma cells). Having excluded other causes of purulent discharge and due to the findings on physical examination and vaginal microscopy, a therapeutic approach for DIV with topical clindamycin, 2%, (Dalacin® vaginal cream, Pfizer) was started, and proved to be successful. After 4 weeks of daily treatment, the patient showed significant improvement in all symptoms. The use of a tampon in the vagina also relieved the symptoms from the vulvar pain.
Conclusions: DIV should be considered as a differential diagnosis in women with persisting vaginitis. An interdisciplinary approach seems to benefit this group of patients.
Clinical Variants of the Vulvo-vaginal Gingival Syndrome with Esophageal and Vaginal Stenosis – A Series of 8 cases
Nina Madnani, MD. Dermatology consultant, P.D. Hinduja National hospital & MRC, Mumbai, India
Objectives: Very few cases of vulvo-vaginal-gingival syndrome have been reported in the literature. Recent reports include complications such as vaginal stenosis. None have been reported with esophageal stenosis.
Methods: A retrospective analysis over 5 years of 8 cases of vulvo-vaginal-gingival syndrome, has been completed. The ages ranged between 48 to 68 years and disease duration 3–8 yrs. 6/8 cases were menopausal. All cases had gingival involvement, of which 3/8 had become edentulous. All had vulvar erosions and dyspareunia and1/8 had vaginal stenosis. 4/8 patients had esophageal involvement with one requiring regular esophageal dilatation. 4/8 had classical lichen planus (LP) lesions on their skin. 1/8 patients also had i lichen sclerosus.
Results: All patients were treated with topicals with none/ minimal relief. The author used mycophenolate mofetil in 1/8, pulse methotrexate in 6/8, and cyclosporine in 1/8 patient. Methotrexate has been effective in relieving the pain and inflammation, and the patients are under maintenance.
Conclusions: Topical applications may not be enough to control inflammation, and systemic immunomodulators may be required. Questioning patients about dysphagia may reveal early esophageal involvement.
Diagnostic Criteria for Erosive Lichen Planus Affecting the Vulva: An International Electronic-Delphi Consensus Exercise
R.C. Simpson, PhD1, BMBS K.S. Thomas, PhD1, P. Leighton, PhD2, R. Murphy, PhD MBChB3. 1Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, UK; 2Division of Primary Care, University of Nottingham, Nottingham, UK; and 3Department of Dermatology, Nottingham University Hospitals, Nottingham, UK.
Objectives: To reach consensus on clinico-pathological diagnostic criteria for erosive lichen planus of the vulva (ELPV) affecting the vulva.
Methods: The erosive subset of lichen planus is a chronic condition that is often refractory to treatment. There is no defined set of criteria for diagnosing ELPV and there is geographical variation in management.
This was a three-stage international electronic-Delphi exercise with formal feedback process. In the first two rounds participants were asked to rate the importance of a list of clinicopathological criteria which had been identified through a literature review and structured interviews with UK clinicians. Responses from round one were summarized and presented in round two, along with additional criteria suggested by participants. In round three, participants were asked to rate the items that had reached consensus as ‘essential’ or ‘supportive’ features in diagnosing ELPV. Consensus was defined as 75% agreement of participants on the importance of an item.
Results: A total of 73 experts representing dermatology, gynecology, histopathology and genitourinary medicine participated; 69 (95%) completed all three rounds. No items reached consensus as an ‘essential’ diagnostic criteria. Consensus was achieved for the following as ‘supportive’ diagnostic criteria: i) scarring/loss of normal architecture; ii) presence of a hyperkeratotic border to lesions or Wickham’s striae in surrounding skin; iii) involvement of other mucosal surfaces; iv) well-demarcated erosions/erythematous areas at the vaginal introitus; v) symptoms of pain/burning; vi) presence of vaginal inflammation; vii) presence of a well-defined inflammatory band involving the dermal-epidermal junction consisting viii) a predominance of lymphocytes at the dermal-epidermal junction and ix) signs of basal layer degeneration at the dermal-epidermal junction. Respondents thought that at least three of these nine supportive features should be present to make a diagnosis of ELPV, although the formal feedback process suggested this number should be subject to further discussion.
Conclusion: In this study we have reached consensus on a diagnostic dataset for ELPV that can be adopted into clinical practice and clinical trials.
Treatment of Hailey-Hailey Disease of the Vulva: a Retrospective Case Series
Karla Solheim, MD, Diane Elas, ARNP, Colleen Stockdale, MD, MS Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA
Objectives: Review the treatment and disease course 5 women with Hailey-Hailey disease (familial benign chronic pemphigus) of the vulva, a rare autosomal dominant dermatosis characterized by malformation of desmosomes and bullae, particularly in intertriginous areas.
Methods: Review of 5 women followed at a single academic institution over a period of 17 years.
Results: Of the 5 patients, 4 carried a diagnosis of Hailey-Hailey at time of presentation to our institution, and one was diagnosed on biopsy. Three were members of a family group. Four were treated in the gynecology department, and 1 was treated in the dermatology department. Patients initially presented in years 1997–2002 and have been followed through years 1998 – 2014. Initial treatment of choice was a topical steroid (betamethasone in 3, fluocinonide in 1, and hydrocortisone in 1), vulvar skin care guidelines, baking soda soaks, a skin protectant such as A&D ointment or zinc oxide, and additional treatment (crotamiton in 1, clotrimazole in 2, and Polysporin in 1). Final treatment regimens in 3 patients followed long-term were zinc oxide ointment in all 3, oral fluconazole prn in 1, betamethasone-clotrimazole ointment in 2, and nystatin-triamcinolone ointment in 1, with good control achieved on this.
Treatment courses were complicated by superimposed candida infections, bacterial infections, and lichen simplex chronicus flares. These were treated with antifungals, topical clindamycin and metronidazole, and steroid-antifungal bursts, respectively. All patients followed long-term (3 of 5) achieved successful remission with occasional flares.
Conclusions: Treatment of Hailey-Hailey disease must be tailored to the individual patient. Adherence to vulvar skin care guidelines is critical for the remission of Hailey-Hailey disease. Treatment is long-term and may be complicated by episodes of fungal and bacterial superinfection and lichen simplex chronicus.
Differences in the Prevalence of Aerobic Vaginitis, Bacterial Vaginosis and the Presence of Candida Species in the Vaginal Fluid in Relation to Women’s Age and the Presence of Symptoms
Pedro Vieira-Baptista, MD1, Joana Lima-Silva, MD1, Cândida Pinto, MD1, Jorge Beires, PhD1, José Martinez-de-Oliveira, PhD2,3, Gilbert Donders, PhD4. 1Serviço de Ginecologia e Obstetrícia, Centro Hospitalar de São João, Porto, Portugal; 2Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal; 3Departamento de Saúde da Criança e da Mulher, Centro Hospitalar Cova da Beira, Covilhã, Portugal; and 4Femicare vzw, Clinical Research for Women, Tienen, Belgium.
Objectives: To evaluate the prevalence of moderate/severe aerobic vaginitis (msAV), bacterial vaginosis (BV) and the presence of Candida spp. in the vaginal fluid of symptomatic and asymptomatic women and their interrelations.
Methods: Wet mounts were performed in asymptomatic women sent for Pap smear (control group); the case group included women sent for Pap smears or for other reasons, who had symptoms not attributable to dermatoses.
Results: Globally, in symptomatic (15.8%[67/424]) and asymptomatic women (84.2% [357/424]), the prevalences of msAV, BV and of the presence of Candida spp. were: 9.4% (40/424), 10.1% (43/424) and 30.0% (127/424), respectively. In symptomatic women, msAV was present in 9.0% (6/67), BV in 10.4% (7/67) and Candida spp. in 46.3% (31/67). In the asymptomatic group, the prevalences were of 9.5% (34/357), 10.1% (36/357) and 26.9% (96/357), respectively. The prevalence of msAV and BV were quite constant in all age groups. The presence of Candida spp. increased until 31–35 years (40.5% [30/74]) and then steadily decreased. Candida spp coexisted with msAV in 22.5% of cases (9/40) and with BV in 11.6% (5/43), without a statistical significance (p=0.186). In women without msAV or BV, Candida spp. was found in 33.1% (113/341), p=0.004. The coexistence of Candida spp. with AV or BV did not increase the likelihood of being symptomatic (RR=1.09; 95% IC 0.47–1.54).
Conclusions: msAV is as prevalent as BV. Their prevalences are constant, in all age groups. msAV, as well as BV, is asymptomatic most of the times, which can be a challenge due to its potential adverse impact in pregnancy outcomes. The presence of Candida has a peak of prevalence at 31–35 years old. The prevalence of Candida spp. in women with msAV or BV was lower than in the rest of women; coexistence did not increase the likelihood of being symptomatic.
Vulvovaginitis: Candida Species Distribution and Prevalence at Saint Louis University Obstetrics and Gynecology
S. Hoffstetter, PhD, M. Shah, MD, C. LeFevre, MD, C. Miller, MSW. Department of Obstetrics, Gynecology & Women’s Health, Saint Louis University School of Medicine, St. Louis, MO.
Objectives: To determine the distribution & prevalence of Candida (C.) species & antifungal susceptibility among patients seen at Saint Louis University’ s Vulvar & Vaginal Disorders Specialty Center with a positive yeast culture. Trends for developing resistance were studied.
Methods: Retrospective study of 324 patients with positive yeast cultures (total cultures = 360) presenting to Saint Louis University Vulvar & Vaginal Disorders Specialty Center between 1- 1–2005 & 3-1- 2014. Data were obtained from Quest Diagnostics. Name, date, identification of yeast isolate(s), demographics, and comorbid conditions were collected from charts. Patients with >1 positive culture were considered to have recurrent candida vulvovaginitis. Antifungals tested for susceptibility were anidulafungin, micafungin, caspofungin, flucytosine, posaconazoel, voriconazole, itraconazole, fluconazole and amphotericin. Chi-square test was used for categorical variables identified.
Results: Candida isolates identified: C. albicans (286), C. glabrata (43), C. parapsilosis (6), C. Krusei (4), Saccharomyces cerevisiae (7), C. tropicalis (4), C. lusitanaie (3), C. guilliermondi (1), Rhodotorula (2), Cryptococcus albidus (1), C. kefyr (1) and other (5). Of the 324 patients, 27 (8%) had recurrent vulvovaginitis. Consistent with other studies, C. albicans was the most frequent species of yeast isolated in this study (88.3%), followed by C. glabrata (13%). All other non-albicans & non-glabrata species represented 0.9% of positive cultures. Of the C. albicans isolates 4.3% were resistant to flucytosine, 1% to itraconazole & only 0.5% to fluconazole. C. glabrata showed more resistance with 3.4% resistant to fluconazole, 6.9% to itraconazole, & 0% to flucytosine. Comorbidities were similar among recurrent & non-recurrent patients with the exception of depression (p < 0.05).
Conclusions: These results support the use of azoles for treatment of candida vulvovaginitis. Recurrent episodes are more often caused by non-albicans species; therefore cultures should be obtained from these patients.
Clinical Presentation and Pathologic Features of Vulvar Basal Cell Carcinoma
Hans Peter Sinn, MD, PhD1, Christine Mayer, MD2, Friedrich Kommoss, MD PhD3. 1Department of Pathology, University of Heidelberg, Germany; 2Department of Gynecology and Obstetrics, University of Heidelberg, Germany; and 3Synlab Institute of Pathology, Mannheim, Germany.
Objectives: Vulvar basal cell cancers (BCCs) are rare tumors with an unclear etiology. The purpose of this study was to investigate the clinical findings, and pathological features in a series of BCCs at our institutions.
Methods: Thirty-five cases of BCCs could be identified. Clinical data and histologic features were reviewed.
Results: The median age of patients with BCCs at diagnosis was 75 years (range: 48 – 91 years). This compared to a median age of 67 years for primary squamous cell carcinomas of the vulva in the same time frame (range: 24–94 years). BCCs occurred most frequently on the labia majora, while only 5 cases located at the labia minora were recorded, and 4 cases next to the clitoris. The median tumor size was 0.85 cm (range: 0.2 - 2.5 cm). The most common histologic type was nodular, followed by superficial BCC. Clinically, the lesions presented as plaques, elevated lesions, erythroplakia, and the diagnosis of BCC was only rarely suspected. Rarely, the lesion was ulcerated or suspicious for carcinoma. In two cases multiple BCCs were present. No case with lymph node metastasis was observed.
Conclusions: Vulvar BCC is not particularly rare, and is characterized by an indolent behavior. Attention should be paid to the histologic diagnosis, since vulvar BCC usually is not suspected clinically. The treatment of choice is complete local excision.
Basal Cell Carcinoma of the Vulva: A Retrospective Study of 11 cases
Ramapadma Namuduri, MD, MRCOG(UK)1, Mark Koh, MRCPCH, FAMS2, YK Lim, MRCOG, M.Med, FRCOG, FAMS1, KL Yam1, Norman Warford, MD, FRCPath3. 1Department of Gynecological Oncology, KK Women’s and Children’s Hospital, Singapore; 2Department of Dermatology, KK Women’s and Children’s Hospital, Singapore; and 3Department of Pathology, KK Women’s and Children’s Hospital, Singapore.
Objectives: Review the clinical features, diagnosis, management and outcomes for 11 cases of basal cell carcinoma (BCC) of the vulva managed at Gynecological Cancer Centre (GCC), at KK Women’s and Children’s Hospital (KKWCH) between 2000 and 2014.
Methods: Eleven cases of vulvar BCC were retrospectively reviewed and analyzed. Data were obtained from a gynecological cancer data base maintained at GCC.
Results: BCC of the vulva is uncommon vulvar neoplasm with an incidence of 8% from the gynecological cancer registry at our center. Of the 11 patients, no one died of their BCC. The mean age at diagnosis was 68 years (range 43 to 78). Ten patients were Chinese. One patient was Malaysian. Average time from onset of symptoms to diagnosis was 13.8 months (range 3–60 months). Diagnosis was made in all cases by biopsy. The most common presenting complaints were a lump and pruritus. All cases were managed surgically. Recurrence was noted in only one patient.
Conclusions: The prognosis for vulvar BCC is excellent. Primary treatment of vulvar BCC is wide local excision. Histological diagnosis of all persistent papules, plaques and pigmented lesions are important for early diagnosis. Metastatic disease in very rare, however continued follow-up is suggested.
Vulvar Carcinoma in Pregnant Women Aged Less than 40 Years: Case Report
Malihe Hasanzadeh, MD, Amir Zamiri-Akhlaghi, MD, Soodabeh Shahidsales, MD. Associate Professors of Gynecology Oncology, Women Health Research center, Department of Gynecology Oncology, Ghaem hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
Background: Invasive squamous cell carcinoma of the vulva is primarily a disease of postmenopausal women and thus is rarely associated with pregnancy.
Case: A young woman, under 40 years of age, presented with vulvar carcinoma during pregnancy, but optimal treatment was delayed to the postpartum period. This 37-year-old woman was diagnosed with 3x3 cm vulvar lesion. Two weeks after cesarean section, a subsequent biopsy revealed squamous cell carcinoma. She had a history of an ulcer on her left labium minus in the third month of the pregnancy. She was treated by a modified radical vulvectomy and bilateral groin lymphadenectomy. The size of the invasive SCC lesion was 3×3cm with no lympho-vascularinvasion. All surgical margins of the lesion (2cm) were free. The pathologist reported a follicular hyperplasia in lymph nodes. She was discharged with no additional therapy. Two year later, she had no recurrence of the disease.
Conclusion: This case emphasizes on the need to consider malignancy as a differential diagnosis in vulvar lesions occurring in pregnant women.
Margin Distance in Stages IB and II Vulvar Squamous Cell Carcinoma: Local Recurrence and Survival
Leonardo Micheletti, MD1, M Preti, MD2, B Ghiringhello, MD3, E Corvetto, MD1, E Palmese, MD1, S Privitera, MD3. 1Department of Gynaecology and Obstetrics, University of Torino, Torino, Italy; 2Preventive Gynaecology Unit, European Institute of Oncology, Milan, Italy; and 3Pathology Unit, S. Anna Hospital of Torino, Torino, Italy.
Objectives: To assess the role of free margin distance in disease free survival (DFS) and overall survival (OS) in FIGO stage IB and II patients surgically treated for invasive vulvar squamous cell carcinoma (VSCC).
Methods: Patients with primary FIGO IB and II VSCC who underwent surgery at the Department of Gynecology and Obstetrics, University of Torino between 1981 and 2013 were included in the study. Free surgical margins were defined as the absence of tumoral infiltration at the resection margin. The distance between resection margin and presence of neoplastic cells were measured. Statistical analysis was performed with log-rank test and Kaplan-Meier method.
Results: A series of 131 patients (116 stage IB and 15 stage II ) with no nodal involvement at total bilateral groin lymphadenectomy were included. Total vulvectomy was performed in 55 patients and partial vulvectomy in 76 patients. Survival at 2, 5, and 10 years was respectively 91.5%, 85.6%, and 77.1%. 24 of the 131 women (18%) died of their disease. Local and regional recurrences developed in 54 patients (41.2%). DFS at 2 and 5 years was respectively 81.1% and 62.1%. Patients with positive margins (N=24) vs. patients with negative margins (N=107) showed a statistically significant decreased 5 year OS (p=0.027). However, between these two group of patients no statistically significant difference was found regarding recurrence risk (p=0.154) and DFS (p=0.121). Finally, there was no statistically significant difference between free resection margin <8mm and ≥8mm with respect to recurrence risk (p=0.291), DFS (p=0.329), and 5 years OS (p=0.329).
Conclusions: Data of the present study suggest that in FIGO IB and II VSCC with free resection margins <8 mm, further adjuvant radiation or re-excision could be safely avoided. The recommendation of a pathological free resection margin ≥8 mm, in order to reduce the risk of recurrence and survival, is questionable, at least in VSCC with negative nodes.
Detection of P16ink4a and TIMP-2 DNA Promoter Methylation in Vulvar Lichen Sclerosus
Lívia Sampaio, MD1, Isabel do Val, PhD1, Guillermo Velarde, D.Sc2, Susana Fialho, PhD1, Gutemberg Almeida, PhD3, Fabiana Rodrigues, PhD4, Fernanda Fonseca, MS5, Renata Guimarães, MS6, Yara Furtado, MD7, Maria da Glória Carvalho, PhD8. 1Departmant of Gynecology, Federal Fluminense University, Niteroi, RJ, Brazil; 2Department of Statistics at the Federal Fluminense University, Niteroi, RJ, Brazil; 3Gynecology Institute and Post-Graduate Program in Surgery at the Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 4Pathology Department at the Federal Fluminense University, Niteroi, RJ, Brazil; 5Intern in Medicine at the Federal Fluminense University, Niteroi, RJ, Brazil; 6University of State of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 7University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; and 8Biophysics Department of the Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Objective: To detect the presence of methylation of the P16INK4a and TIMP-2 genes in vulvar lichen sclerosus and evaluate the relationship between age and the methylation of those genes.
Methods: Promoter hypermethylation of P16INK4a and TIMP-2 genes were investigated in 32 vulvar biopsies from patients with LS and no prior treatment. Bisulfite modified DNAs were subjected to methylation-specific PCR.
Results: Among all the samples, we found no amplification of the P16INK4a in only one case, and this was true in three cases for the TIMP-2 gene. Of the 28 samples in which amplification of both genes was found, 39% (11/28) showed methylation only for the TIMP-2 gene. No patient (0/28) showed methylation for the P16INK4a gene alone. In 29% (8/28) of the samples, no methylation of either gene was found, but in 32% (9/28) we found methylation of both the P16INK4a gene and the TIMP-2 gene. This result proved to be statistically significant (p=0.0292). No association was found between the occurrence of methylation of the P16INK4a gene and TIMP-2 gene in terms of age (p=0.4098 and p=0.4244, respectively).
Conclusion: Methylation of P16INK4a and TIMP-2 genes, although not sufficient to ensure prognosis of the disease, should not be underestimated because it may form part of a process of genetic and epigenetic alteration in control of the cell cycle and extra-cellular matrix. Since these precede morphological changes, they may operate as a marker that distinguishes patients at a greater risk of having lichen sclerosus progress to differentiated VIN and/or vulvar cancer.
Long-term Management of Adult Vulvar Lichen Sclerosus
A. Lee, MBBS1,2, J Bradford3, Gayle Fischer, MBBS (Hons) MD, FACD1,2,3. 1Department of Dermatology Royal North Shore Hospital, St Leonards, NSW, Australia; 2Northern Clinical School, University of Sydney, NSW, Australia; and 3The Centre for Vulvovaginal Health, Northern Paediatric Dermatology, Royal North Shore Private Hospital, St Leonards, NSW, Australia.
Objectives: To determine if topical corticosteroid treatment of vulvar lichen sclerosus (VLS) reduces risk of squamous cell carcinoma, improves function and symptoms and achieves preservation of vulvar architecture. The secondary objectives are to suggest an effective treatment regimen that maximizes safety and minimizes adverse effects.
Methods: A prospective, single center study of 507 adult women with biopsy proven VLS was conducted over 8 years. All subjects were recorded for symptoms, signs, squamous cell cancer, treatment regimens, compliance, response to treatment, maintenance therapy, progress of adhesions or scarring, and side effects. All patients were assessed regularly and monitored with clinical photography.
Results: The mean age of presentation was 55.4 years and mean duration of follow up 4.7 years. Treatment regimens were individualized with the target outcome being complete objective normality of vulvar skin with no evidence of disease activity. The majority of patients were managed with daily corticosteroid using a combination of weak and moderate potency topical corticosteroid. 70.4% of patients were fully compliant and 29.6% partially compliant. Squamous cell carcinoma occurred in 7 non-compliant patients, but in none of the compliant patients (p<0.0001). Improvement of symptoms occurred in 93% of compliant patients compared to 58% of non-compliant patients (p<0.0001). Progress of adhesions and scarring occurred in 3.4% of compliant patients and 40.7% of non-compliant patients (p<0.0001). Reversible corticosteroid induced atrophy occurred in 1% of compliant and 2.0% of non-compliant patients.
Conclusions: This large prospective study of adults with VLS suggests that an individualized regimen of topical corticosteroid treatment complied with over time with regular follow-up may modify the course of the VLS. This method was safe, effective in improving symptoms and in preventing progression of disease. In this cohort there was a significant difference in rates of squamous cell carcinoma between compliant and non-compliant patients.
Surgery for the Relief of Sexual Problems in Women with Lichen Sclerosus
Matthé P.M. Burger, MD PhD1, M. Brauer, PhD2, M. Obdeijn, MD, PhD3, H.W. van Lunsen, MD PhD2, E.T.M. Laan, PhD2. 1Department of Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam; 2Department of of Sexology and Psychosomatic Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam; and 3Department of Plastic and Reconstructive Surgery, Academic Medical Center, University of Amsterdam, The Netherlands.
Objectives: Firstly, to analyse the physical effects, including postoperative complications, of the surgical interventions for the relief of sexual problems. Secondly, to gain insight into how patients themselves evaluate the outcomes of vulvar surgery in terms of its ability to relieve sexual pain and other consequences for their sex-life.
Methods: Women were considered eligible for surgery if their lichen sclerosus was considered of central importance for their sexual problems. The psychosexual effects of the intervention were explored using audiotaped qualitative individual interviews, done between 10 months and 5 years (median 2 years and 5 months) after surgery. Interview data were analyzed using the constant comparative method.
Results: This report concerns 19 patients (30–72 years, mean 56 years), all of whom underwent posterior vestibuloplasty (perineoplasty). Some women underwent in addition an anterior vestibuloplasty with grafting of vaginal epithelium (n=4) and/or dehooding of the glans (n=4).
The surgery resulted in a reduction of sexual pain complaints in 13 (68%) of the sample; there was a shift from preoperative sexual pain to postoperative discomfort. Eighteen (95%) women reported a reduction of lichen sclerosus symptoms in daily life. The women who had resumed intercourse reported improved sexual functioning, increased (coital) sexual activity and intimacy with the partner, and reinstated feelings of being an adequate woman and sexual partner.
Conclusions: Vulvar surgery is an effective treatment for the majority of women with LS who experience sexual pain due to anatomical or epithelial changes and who wish to resume intercourse. To estimate whether women may benefit from such surgery and/or if (additional) sexual counseling is indicated, pre-operative sexological couple-based consultation is needed. This consultation should exclude for comorbid vaginismus and generalized unprovoked vulvodynia as well as to index the couple’s pre-existing sex-life including sexual communication skills and the ability to incorporate non-coital pain-free sexual activities.
The Use of 2-D Ultrasound in Delineating the Clitoris in Moderate to Severe Lichen Sclerosus (LS) and Lichen Planus (LP)
Karen L. Gibbon, MD, FRCP1, Tony Hollingworth, PhD, FRCOG2, Carmel Evans, Modality Lead Sonographer, FRCP3, Nicholas Reading, FRCR3. 1Department of Dermatology, Barts Health NHS Trust, London; 2Department of Gynaecology, Barts Health NHS Trust; 3Department of Ultrasonography, Barts Health NHS Trust; and 4Department of Radiology, Barts Health NHS Trust.
Objectives: The destructive inflammatory process seen in moderate and severe vulvar lichenoid dermatoses frequently leads to architectural change resulting in burying of the clitoris and loss of the clitoral hood or prepuce. The resulting psychosexual morbidity is difficult to manage if the patient believes their clitoris has been ‘lost’ or irreversibly damaged. The term “clitoral complex” refers to the distal vagina, urethra and clitoris as these structures act as one unit. Clitoral anatomy has been demonstrated in a small number of retrospective pelvic MRI studies in patients and in healthy premenopausal volunteers. To date there are no published studies on the use of ultrasound in delineating the clitoris in affected women. This prospective study describes the use of 2-D ultrasound in delineating the clitoral complex in an ongoing small series of affected women prior to revision surgery and division of anterior midline adhesions.
Methods: To date 4 women with significant anterior architectural change and psychosexual morbidity have been identified in a dedicated vulvar clinic. A 2-D ultrasound scan has been performed by the modality lead sonographer using a GE LOGIQ E9 ultrasound machine, with a ML6-15 MHz linear probe in the presence of a chaperone.
Results: The scan took approximately 5 minutes to perform and showed preservation of all clitoral structures apart from the prepuce. Two women have been reviewed following surgery and show good visibility of the glans and improved psychosexual functioning. Other patients are under review.
Conclusions: Delineating the clitoral complex using ultrasound is a safe, relatively cheap modality to use and well tolerated. A clitoral ultrasound scan is completed in approximately 5 minutes, in comparison to approximately 30 minutes for a pelvic MRI scan which is contraindicated for some (claustrophobics, pacemakers, aneurysm clips etc.) patients.
A Comparison Between Focused Ultrasound and Halcinonide Cream in Treatment of Vulvar Lichen Sclerosus
Chengzhi Li, MD, PhD, Yi Liu, MS, Liping Chen, MS, Zhibiao Wang, PhD. The College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing, China.
Objectives: To evaluate the efficacy and safety of focused ultrasound in treatment of vulvar lichen sclerosus.
Methods: Sixty patients with pathologically diagnosed vulvar lichen sclerosus were randomly allocated into the focused ultrasound group (30 patients) and halcinonide cream group (30 patients).The signs, symptoms and the life quality of patients were assessed before treatment, 1 month and 3 months after treatment. The effect and the adverse reaction of treatment between the two groups were evaluated respectively after treatment.
Results: The signs, symptoms and life quality of patients were improved in both groups after 1 and 3 months.The focused ultrasound therapy showed superior results in lesion amelioration at 1 month (P < 0.05),as well as lesion amelioration and therapeutic effect after 3 months (P < 0.05).The therapeutic effect of focused ultrasound was better in those with > 10 years disease after 3 months treatment (P < 0.05).There was no paravaginal tissue injury in the focused ultrasound group.
Conclusions: Focused ultrasound is one of the safe and effective methods in the treatment of vulvar lichen sclerosus. Compared with drugs, focused ultrasound treatment has the characteristics of significantly improving skin lesions and improving the cure rate.
The Bioeffects of Focused Ultrasound on Proliferation of Endothelial Cells for the Treatment of Lichen Sclerosus
Chengzhi Li, MD, PhD, Yi Liu, MS, Liping Chen, MS, Zhibiao Wang, MD, PhD. The College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing, China
Background: Lichen sclerosus is a chronic inflammatory disease, which presents a therapeutic challenge. Focused ultrasound (FU) therapy has shown promise in the disease management.
Objectives: To study the bioeffects of FU near field with commonly used exposure parameters on the endothelial cells.
Methods: FU near field of different frequency (10.1MHz and11.2MHz) and power (4.3W and 5W) was performed to stimulate in vitro human umbilical vein endothelial cells ( ECV304 ) cell lines for 5, 10, 15, 20, 25, and 30 seconds; and the cell proliferation was measured by MTT assay after 24 hours. One-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis SDS-PAGE) was performed to separate proteins from irradiated and normal endothelial cells. Different proteins (pre- and post- irradiation) were identified by liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI-IT MS/MS).
Results: The relative survival ratio of ECV304 measured by MTT assay showed a high value and statistically significant increase when focused ultrasound was applied at 11.2 MHz and 4.3 W for 10 s. The frequency and irradiation duration, but not the power, had significant influence on cell relative survival. Protein difference banding, decolorizing, and enzyme solution processing after LC-ESI-IT MS/MS and data retrieval in the SWISSPROT protein database successfully identified seven different proteins: AP - 2 complex subunit β – 1 (AP-2Compound), zinc finger protein 649 (ZNF649) cells, ubiquitin-like modifier activating enzyme 1 (UBA1), transitional endoplasmic reticulum ATPase (TER ATPase), α-actinin - 1 (Actn1), actin, and proenkephalin A precusor. 43% participated in cell signal transduction, 29% were cytoskeletal protein, and 28% participated in cell motility.
Conclusions: FU can stimulate the proliferation of endothelial cells by induced cell skeleton system and activated related signal path. Further studies are recommended to understand and confirm the involvement of various mechanisms in cellar signaling and proliferation.
Vitamin D and Lichen Sclerosus: Preliminary Findings
Allan B MacLean, MD, Maxine Chan, MBBS, John Barry, PhD, Michael Thomas, PhD. Departments of Gynaecology and Chemical Pathology, Royal Free Campus, University College, London, UK.
Objectives: Lichen sclerosus (LS) has features of an autoimmune disorder. It shows clustering with other autoimmune disorders (e.g. thyroid disease), and extracellular matrix protein antibodies have been identified. It is found more frequently in Europe, North and South America and Oceania than in equatorial countries, suggesting that diet and climate might be important factors. Vitamin D deficiency has been associated with autoimmune disorders and some cancers, and is caused by inadequate dietary intake and sun exposure. We measured vitamin D1 in women with LS.
Methods: Patients attending a Vulval Clinic with LS were asked about country of birth, duration of residence in England, ethnic origin, timing of diagnosis of LS / new or follow-up visit, other illnesses including autoimmune disorders, intake of oily fish, egg yolk, cod liver oil or vitamin D supplements (daily, weekly, monthly), and holidays or time spent in the sun (how long ago, duration and use of sun protection). Blood was taken for serum levels of 25-hydroxyvitamin D (25OHD) using the E170 Roche Module platform and measured as nmol/l. Ethics Committee approval was obtained.
Results: 117 women with LS had levels of 25OHD measured: only 21% had optimal levels >75, and 42% had moderate to severe deficiency (<40). Only 23 “control patients” were recruited, but some of these also had moderate-severe deficiency.
Conclusions: We have identified some LS patients with vitamin D deficiency, but similar findings among the controls. The fact that the 3 lowest levels (9,10 &19) in the controls had biopsy diagnoses of lichen simplex chronicus and lichen planus may indicate that controls need to be distinctly different clinically. Further analysis of levels is required with the month of sampling, and correlation with adequate / inadequate diet and sun exposure, before we can suggest that LS is associated with vitamin D deficiency.
Autologous Platelet Rich Plasma (PRP) Intradermal Injections for the Treatment of Vulvar Lichen Sclerosus
Michelle King, MSc, Hillary Tolson, Charles Runels, MD, Meghan Gloth, MD, Richard Pfau, MD, Andrew T Goldstein, MD. Center for Vulvovaginal Disorders, Washington, DC.
Objectives: Exploratory study designed to evaluate the efficacy and safety of autologous Platelet Rich Plasma (PRP) injections for the treatment of vulvar lichen sclerosus.
Methods: Nine patients with biopsy proven active vulvar lichen sclerosus were recruited. This study consists of a 2 week screening period and a 12-week treatment period. Patients receive two separate treatments of PRP separated by 6 weeks. Each treatment consists 5 ml of autologous PRP (Magellan® Autologus Platelet Separator System. Arteriocyte Medical Systems. Hopkinton, MA) injected sub-dermally and intra-dermally. A repeat biopsy was performed 6 weeks after the second PRP injection. The primary efficacy variable as measured by two blinded pathologists is the change in inflammation between pre and post treatment biopsies. Secondary endpoints included changes from baseline in pruritus and vulvar burning using VAS scales and change of Investigator’s Global Assessment (IGA) of the severity of the disease (0 to 3 scale).
Results: Seven out of the 9 participants completed the protocol and 2 participants were lost to follow up prior to having post-treatment biopsies. Of the 7 patients who completed the protocol, two blinded pathologists determined that 4 women had decreased inflammation on their post treatment biopsies, one woman had no change in inflammation, and 2 women had “minimal” increase in inflammation on their post treatment biopsies. A T-test compared the IGA scores for the patients pre and post treatment and showed a significant difference between the pre (mean 2.4) and post (mean=1.6) p = 0.016.
Conclusions: The effectiveness of PRP is based on its high level of growth factors such as PDF, TGF-β, and EGF. These growth factors are important in modulating mesenchymal cell proliferation, and extracellular matrix synthesis during healing. The vast majority of published literature shows that autologous PRP has minimal risk of scar tissue formation or serious adverse events. The results of this exploratory study suggest that PRP injections decreased histopathologic inflammation in women with vulvar LS without the potential side effects associated with topical or systemic immunomodulators.
Clinico-pathologic And Molecular Characteristics Of Vaginal Melanoma
Tay Sun Kuie, Professor, Department of Obstetrics & Gynecology, Singapore General Hospital, Singapore.
Objectives: This study reported the clinical, pathologic and molecular characteristics of seven vaginal melanoma managed in a single institute.
Methods: Vaginal melanoma treated and followed up between January 2008 and December 2014 was studied. Descriptive analysis was performed on patient demography, tumor presenting symptoms and pathologic and molecular characteristics, treatment modality and current disease status.
Results: Seven cases of vaginal melanoma were managed with comprehensive radiological studies with MRI, CT and/or PET-CT scans. Five (71.4%) patients had definitive surgeries: anterior pelvic exenteration with groin and pelvic lymphadenectomy (n=2), hysterectomy/vaginectomy and groin and pelvic lymphadenectomy (n=1), and local wide excision with lymphadenectomy (n=2). The median age of the patients was 46 (range 38–58) years. The presenting symptoms were vaginal bleeding or brown discharge (n=6) and a vaginal lump (n=1). The median largest tumor dimension was 4-cm (range 2–10). One tumor was darkly pigmented, 5 were light brown and one was non-pigmented. The cases included FIGO stage-I (n=1), stage-II (n=1), stage-III (n=4) and stage-IVB (n=1). Histopathology showed round/oval tumor cells with prominent nucleoli and sparse brown or dark intra-cytoplasmic pigments, and obvious mitosis. Immunohistochemical staining was positive for S100, HMB45 and Melan-A. CKIT mutation was positive for c.1727 T–>C (p.L576P, Exon 11 substitution) in one case. The median follow-up period was 6 (range 1–78) months. One patient with an untreated metastatic 10-cm tumor died at 3 months and one patient treated with Darcabacine and cisplatin for a metastatic 10-cm tumor was alive at 18 months with progressive disease. Five patients remained disease free.
Conclusions: Vaginal melanoma presents in middle-aged women with vaginal bleeding and advanced disease. Dark tumor pigmentation is uncommon, though brown intra-cytoplasmic pigmentation is present. Positive immunohistochemical staining with S100, HMB45 and Melan-A is diagnostic. Optimal treatment is adequate surgical clearance. Prognosis is poor for large tumor with metastasis.