Evaluating the Effectiveness of a Novel Skin Barrier Protectant in a Patient with Acute Radiodermatitis of the Vulva: A Case Report.

OBJECTIVE: To evaluate the use of a novel skin barrier protectant in a patient treated with radiotherapy for vulvar cancer. METHODS: This case report was conducted in a radiotherapy department with two women undergoing radiotherapy for vulvar carcinoma. A novel skin barrier protectant was evaluated in one patient; the other underwent the institutional standard skin care protocol. Skin reactions and pain were evaluated using the Radiotherapy Oncology Group Criteria. MAIN RESULTS: The patient who was treated with the skin protectant showed accelerated healing toward the end of radiotherapy, and this was accompanied with a decrease in pain (maximum pain score 6/10). In comparison, the patient treated with the standard skin care protocol had an extended healing process, experienced a higher pain level (maximum pain score 9/10), and required more nursing care. CONCLUSIONS: This case report is the first to suggest that this novel skin barrier protectant could effectively manage acute radiodermatitis in patients with cancer. This case report hopes to lay the foundation for future randomized controlled trials with a larger and broader patient population.

Common Benign Chronic Vulvar Disorders.

Common benign chronic vulvar conditions include genitourinary syndrome of menopause (formerly called vulvovaginal atrophy), lichen sclerosus, lichen planus, lichen simplex chronicus, and vulvodynia. Genitourinary syndrome of menopause results from the hypoestrogenic state that leads to atrophy of normal vulvar and vaginal tissues. It is typically treated with lubricants, moisturizers, and intravaginal estrogen. Lichen sclerosus is an inflammatory condition characterized by intense vulvar itching. It is treated with topical steroids or, in some cases, topical calcineurin inhibitors. Patients with lichen sclerosus are at risk of vulvar squamous cell carcinoma and should be monitored closely for malignancy. Lichen planus is an inflammatory autoimmune disorder that can affect the vulva and vagina in addition to other skin and mucosal surfaces. The first-line treatment is topical steroids, and significant scarring can occur if left untreated. Lichen simplex chronicus manifests as persistent itching and scratching of the vulvar skin that leads to thickened epithelium. Breaking the itch-scratch cycle, often with topical steroids, is the key to treatment. Vulvodynia is a common vulvar pain disorder and is a diagnosis of exclusion. A multimodal treatment approach typically includes vulvar hygiene, physical therapy, psychosocial interventions, and antineuropathy medications.

A single-arm clinical trial investigating the effectiveness of a non-hormonal, hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors.

OBJECTIVE: To assess the efficacy of non-hormonal, hyaluronic acid (HLA)-based vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in women with a history of endometrial cancer. METHODS: For this single-arm, prospective, longitudinal trial, we enrolled disease-free women with a history of endometrial cancer who underwent surgery (total hysterectomy) and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1]; 4-6 weeks [T2]; 12-14 weeks [T3]; 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). RESULTS: Of 43 patients, mean age was 59 years (range, 38-78); 54% (23/43) were partnered; and 49% (21/43) were sexually active. VAS, VuAS, MSCL, and SAQ (Sexual Activity Questionnaire) scores significantly improved from baseline to each assessment point (all p < .002). FSFI total mean scores significantly increased from T1 to T2 (p < .05) and from T1 to T4 (p < .03). At T1, 41% (16/39) felt confident about future sexual activity compared to 68% (17/25) at T4 (p = .096). Severely elevated vaginal pH (>6.5) decreased from 30% (13/43) at T1 to 19% (5/26) at T4 (p = .41). CONCLUSION: The HLA-based gel improved vulvovaginal health and sexual function of endometrial cancer survivors in perceived symptoms and clinical exam outcomes. HLA administration 1-2×/week is recommended for women in natural menopause; a 3-5×/week schedule appears more effective for symptom relief in cancer survivors.

Patient interest in the Lowdown on Down There: attendance at a vulvovaginal and sexual health workshop post-cancer treatment.

PURPOSE: Sexual difficulties and vulvovaginal changes are common for women undergoing, and following, cancer treatments. These changes have significant impacts on quality of life and significant relationships. The current study aimed to (1) evaluate women's interest and attendance in a group-based educational workshop to address changes in vulvovaginal health and sexuality after cancer, and (2) describe participant characteristics and presenting concerns. METHODS: Two hundred eighteen women with a history of cancer expressed interest in receiving information about the workshop and completed phone screening. Interested women (n = 156) completed an online questionnaire package examining vulvovaginal health and sexual function prior to attending the workshop. RESULTS: Approximately 75% of the women who completed screening attended the workshop. Clinically significant sexual distress was reported by 91% of participants, and 97% of sexually active participants exceeded the threshold for sexual dysfunction (per FSFI). Women within 1-2 years of diagnosis tended to report less sexual distress, less severe vulvovaginal symptoms, and less impact from these symptoms compared to women farther out from diagnosis. While the majority of women reported vaginal dryness and pain during intercourse, only a minority reported engaging in health promotion strategies sufficient to expect symptom improvement. CONCLUSIONS: The current study suggests that group-based educational workshops for vulvovaginal and sexual concerns are utilized by patients and should be offered to women well into disease survivorship. Workshops targeting vulvovaginal symptoms and sexual concerns may be a cost-effective method of reducing sexual distress and improving patients' sexual function and quality of life.

Reduced Trichomonas vaginalis viability in mice pretreated with parasite DNA.

Trichomonas vaginalis is an extracellular parasite that colonizes the human urogenital tract leading to trichomoniasis, the most common sexually-transmitted non-viral disease worldwide. The immune response plays a critical role in the host defense against this parasite. Trichomonas' DNA contains unmethylated CpG motifs (CpGDNA) that in other microorganisms act as modulators of the immune response. However, the molecular mechanisms responsible for CpGDNA immune modulation are still unclear. As macrophages participate in the first line of defense against infection, we investigated the type of immune response of murine macrophages to T. vaginalis DNA (TvDNA). We observed high expression of the proinflammatory cytokines IL-6 and IL-12p40 in macrophages stimulated with TvDNA. In contrast, the anti-inflammatory response, assessed by IL-10 and IL-13 mRNA expression was delayed. This suggests that the immune response induced by TvDNA is modulated through cytokine production, mediated partly by NADPH-oxidase activity, as TvDNA induced reactive species of oxygen production and a rounded morphology in macrophages indicative of an M1 phenotype. Furthermore, infected mice pretreated with TvDNA displayed persistent vulvar inflammation and decreased parasite viability consistent with higher proinflammatory cytokine levels during infection compared to untreated mice. Overall, our findings suggest that TvDNA pretreatment modulates the immune response favouring parasite elimination.

Refinamentos estéticos na aparência da vulva na cirurgia de adequação genital / Esthetic refinements to the appearance of the vulva in sex reassignment surgery

Introdução: A cirurgia de adequação genital tem se mostrado uma opção segura e confiável, com redução drástica na disforia e melhora da qualidade de vida das pessoas transgênero. A técnica mais estudada e utilizada é a inversão peniana com suas modificações, com aparência estética e funcionalidade adequadas, porém sem padronização da técnica cirúrgica. Índices de até 38% de satisfação parcial e 15% de insatisfação podem levar até 66% dos casos a realizar procedimentos adicionais. O objetivo é sugerir refinamentos estéticos na aparência da vulva e comparar com algumas das técnicas descritas, buscando aumentar a satisfação estética e funcional pós-operatória. Métodos: Estudo retrospectivo com 7 pacientes submetidas à cirurgia de readequação sexual entre agosto de 2017 e fevereiro de 2018. O clitóris é feito com a glande em formato de tridente, utilizando a coroa para construir os corpos cavernosos do clitóris e aumentar a área de sensação erógena. Faixa de prepúcio é usada para aumentar a cobertura do clitóris e cobrir a face interna dos pequenos lábios, que são definidos com o uso de suturas. Resultados: Sensibilidade adequada e satisfação com o resultado e capacidade de orgasmo em todas as pacientes observadas. Não houve estenose, fístula ou necrose do clitóris com essa técnica. Somente 1 caso precisou de procedimento adicional para melhor definição estética. Conclusão: A técnica apresentada tem alta satisfação das pacientes e sensibilidade erógena, com algumas vantagens em relação a outras técnicas. Porém, estudos prospectivos com número maior de pacientes são necessários para definir a técnica cirúrgica mais efetiva.

Introduction: Sex reassignment surgery is a reliable and safe option, which has drastically reduced dysphoria and improved the quality of life of transgender individuals. The most studied and used technique is penile inversion with modifications, which results in appropriate esthetic appearance and functionality, but the surgical technique has not been standardized. Partial satisfaction rates up to 38% and dissatisfaction rates of 15% may cause up to 66% of cases to undergo additional procedures. The objective is to suggest esthetic refinements to the appearance of the vulva and compare some of the techniques described, seeking to increase the postoperative esthetic and functional satisfaction. Methods: A retrospective study with 7 patients undergoing sex reassignment surgery between August 2017 and February 2018 was conducted. The clitoris is constructed with the glans in the form of a trident, using the corona to build the corpus cavernosa of the clitoris and increase the area of erogenous sensation. A section of the prepuce is used to increase the coverage of the clitoris and cover the inner surface of the labia minora, which are defined with the use of sutures. Results: Adequate sensitivity and satisfaction with the result and capacity of orgasm in all patients were observed. There was no stenosis, fistula, or necrosis of the clitoris with this technique. Only 1 case needed an additional procedure for better esthetic definition. Conclusion: The technique presented leads to high patient satisfaction and erogenous sensitivity, with some advantages compared to other techniques. However, prospective studies with larger numbers of patients are needed to define a more effective surgical technique.

Should Genital Hiatus/Perineal Body Be Measured at Rest or on Valsalva?

OBJECTIVE: Genital hiatus (Gh) and perineal body (Pb) are part of the Pelvic Organ Prolapse Quantification assessment system, but it is unclear whether measurements should be taken at rest or on Valsalva. This study was designed to assess the predictive value of Gh and Pb measurements obtained at rest and on Valsalva for signs and symptoms of pelvic organ prolapse (POP). METHODS: This is a retrospective study involving 416 women who presented to a tertiary urogynecology unit with symptoms of pelvic floor dysfunction. Genital hiatus and Pb were measured at rest and on maximal Valsalva. The strength of association between binary markers of POP and measurements of Gh/Pb was estimated using logistic regression analysis. Receiver operator characteristic statistics were used to compare predictive values of Gh and Pb measurements obtained at rest and on Valsalva. RESULTS: A total of 451 women were seen during the study period. Thirty-five were excluded owing to missing data, leaving 416. Fifty-four percent (n = 223) complained of POP symptoms. On examination, 80% (n = 332) had significant POP (stage 2+ in anterior or posterior compartments or stage 1+ in the central compartment). On imaging, significant POP was diagnosed in 66% (n = 275). Mean hiatal area was 22 cm (SD, 7; range, 5-49 cm) at rest and 30 cm (SD, 10; range, 11-69 cm) on Valsalva. Genital hiatus and Pb measured on Valsalva were consistently stronger predictors of prolapse symptoms and objective prolapse (by clinician examination and by ultrasound) than at Gh and Pb measured at rest. The corresponding area under the curve values were significantly larger for Gh/Pb measures on Valsalva after adjusting for multiple confounders. CONCLUSIONS: Genital hiatus/Pb measured on maximal Valsalva is a superior predictor of symptoms and signs of POP compared with Gh/Pb at rest.

Primavera: A new therapeutical approach to vulvo-vaginal atrophy.

Vulvovaginal atrophy is a condition that affects women, although it is mainly associated with the onset of menopause mainly due to hormonal changes vulvovaginal laxity and mucosal atrophy can also affect women at different life stages such as after pregnancy or for cancer patients who have undergone chemo or endocrine therapy. This condition negatively influence quality of life, sexual desire, and self-confidence. Many therapies have been considered mainly with inconclusive or transient results in terms of benefit factor. Recently, a new non-invasive product, containing hyaluronic acid, oligopeptides, and antioxidants was introduced to the market. Its name is "Primavera," by Renaissance, Italy. The aim of this product is to allow a vulvo-vaginal biostimulation and considered simple, safe, and satisfactory.

Managing vulvovaginal atrophy after breast cancer.

Cancer treatment may result in loss of ovarian function through surgical removal of the ovaries, chemotherapy or radiation. While menopausal symptoms, such as hot flushes, night sweats, sleep disturbance, memory concerns and mood issues can be extremely bothersome to some women going through menopause naturally, women who undergo an induced menopause usually experience more sudden and severe symptoms. Pain and vaginal dryness can occur whether a woman has a sexual partner or not. In women with breast cancer, the aetiology of impaired sexual functioning, and lowered sexual desire, is often multifactorial, and may be related to physical and/or psychological reasons. Pain and vaginal dryness in women without a history of breast cancer can usually be safely treated with vaginal estrogens, in the form of a cream, pessary or ring, and simple lubricants or vaginal moisturisers. Safe usage of vaginal estrogen replacement therapy in breast cancer patients has not been studied within randomised clinical trials of long duration; the guidelines below reflect a clinical consensus.

Childhood Asymmetry Labium Majus Enlargement (CALME): Description of Two Cases.

Background: Childhood asymmetry labium majus enlargement (CALME) is an uncommon, benign condition that occurs in pre- and early pubertal girls and is characterized by a painless, fluctuating, non-tender labial swelling with normal overlying skin. Recognition of this benign condition is essential. Differentiation with several other diseases that mimic CALME and require different diagnostic and therapeutic approaches is mandatory. Two cases of CALME are described in this report. Differential diagnoses and therapeutic approaches are highlighted. Case presentation: The first case was an 11-year-old Caucasian girl referred to our hospital for the evaluation of right labium majus, which showed a palpable, painless, soft, non-tender, non-erythematous enlargement measuring approximately 2 cm with indistinct borders. Ultrasound showed a mass 23 × 18 × 12 mm in diameter. Surgical excision of the mass was performed and in the histopathological evaluation, the tissue specimens were composed of haphazardly arranged vascular channels, adipose tissue and nervous elements that were components of the vulvar soft tissue and were compatible with the diagnosis of CALME. Case 2 was a 6-year-old Caucasian girl who presented a post-traumatic painless mass of left labium majus swelling that progressively increased in volume. Ultrasound study evidenced an ill-defined heterogeneous echotexture mass 26 × 15 × 10 mm in diameter and magnetic resonance imaging confirmed these findings. Histopathological examination was performed after bioptic sampling evidencing normal constituents of vulvar soft tissue, including fibroblast, collagen, adipose tissue, blood vessels and nerves compatible with CALME. Conclusions: CALME is a particular clinical condition that occurs mainly in pre-pubertal girls and has a benign course but poses numerous problems in differential diagnosis that can be solved only with careful clinical observation and with a careful use of radiological imaging techniques. Our cases, in agreement with recent literature, suggest that radical excision is not recommended and that surgical biopsy should be taken into consideration only in cases of doubt.

Validation of Clinical Tools for Vaginal and Vulvar Symptom Assessment in Cancer Patients and Survivors.

INTRODUCTION: Health care professionals can play a pivotal role in promoting vulvovaginal health through assessment and appropriate intervention. AIM: To develop and validate brief clinical measurements to facilitate the identification of vulvovaginal symptoms in patients with and survivors of cancer. METHODS: One hundred seventy-five women survivors of cancer attending a Female Sexual Medicine and Women's Health Program from September 26, 2012 through October 31, 2014 completed the Vaginal Assessment Scale (VAS) and the Vulvar Assessment Scale (VuAS)-a modified version of the VAS that targets vulvar symptoms. Pelvic examination results were recorded using a clinical examination checklist. MAIN OUTCOME MEASURES: Internal consistency of the two scales was assessed using Cronbach α, and the correlation between scales and other outcomes was reported. RESULTS: The internal consistency measurements of the VAS and VuAS at the first visit were 0.70 and 0.68, which decreased to 0.53 and 0.66 at the last visit. The VAS composite and VuAS composite scores were moderately correlated with each other (0.42 and 0.45 at first and last visits, respectively). A strong correlation was observed between VAS pain with intercourse and Female Sexual Function Index (FSFI) pain with intercourse (-0.63 and -0.71 at the first and last visits, respectively). Worse pain with examination, worse functioning on the FSFI pain, lubrication, and total scores, and worse vulvar irritation were correlated with more severe symptoms on the VAS and VuAS. CONCLUSION: The VAS and VuAS are simple tools that can be used by clinicians to assess health concerns in women diagnosed with and treated for cancer. Validation is needed across diverse settings and groups of women.

Is vulvovaginal atrophy due to a lack of both estrogens and androgens?

OBJECTIVE: The aim of this study was to review the preclinical data showing the role of both estrogens and androgens in the physiology of the vagina, and, most likely, in vulvovaginal atrophy of menopause. METHODS: Mass spectrometry-based assays (validated according to the FDA guidelines) for the measurement of sex steroids, their precursors, and metabolites were used. In addition to fixation of the vagina for morphological examination, histomorphometry, immunocytochemistry, immunofluorescence, and quantitative reverse transcription polymerase chain reaction were performed. RESULTS: The vaginal epithelium of the animals receiving dehydroepiandrosterone (DHEA) was made of large multilayered columnar mucous cells showing distended cytoplasmic vacuoles representative of an androgenic effect. DHEA also stimulates collagen fiber compactness of the lamina propria (second layer)-an effect essentially due to an androgenic effect, whereas stimulation by DHEA of the muscularis in the third vaginal layer is approximately 70% due to the androgenic conversion of DHEA. Stimulation of the surface area of the nerve endings, on the contrary, is exclusively androgenic. Vaginal weight stimulation by DHEA is about 50% androgenic and 50% estrogenic. CONCLUSIONS: Practically all studies on the influence of steroid hormones in the vagina have focused on luminal epithelial cells. Since all estrogens and androgens in postmenopausal women are made intracellularly and derive from the conversion of circulating DHEA, it is of interest to observe from these preclinical data that DHEA exerts both estrogenic and androgenic activity in the three layers of the vagina, the stimulatory effect on nerve density being 100% androgenic. Taking vaginal weight as a global parameter, the stimulatory effect of DHEA in the rat vagina is about equally estrogenic and androgenic, thus illustrating the importance of androgens in vaginal morphology and function, and the likely importance of androgens in vulvovaginal atrophy of menopause.

Psychological characteristics and motivation of women seeking labiaplasty.

BACKGROUND: Labiaplasty is an increasingly popular surgical intervention but little is known about the characteristics and motivation of women who seek the procedure or the psychosexual outcome. METHOD: A total of 55 women seeking labiaplasty were compared with 70 women who did not desire labiaplasty. Various general measures of psychopathology as well as specific measures (Genital Appearance Satisfaction; Cosmetic Procedure Screening for labiaplasty) were used. Labia measurements of the women seeking labiaplasty were also obtained. RESULTS: Women seeking labiaplasty did not differ from controls on measures of depression or anxiety. They did, however, express increased dissatisfaction towards the appearance of their genitalia, with lower overall sexual satisfaction and a poorer quality of life in terms of body image. Women seeking labiaplasty reported a significantly greater frequency of avoidance behaviours on all the domains assessed, and greater frequency of safety-seeking behaviours for most of the domains. Key motivations reported for labiaplasty were categorized as cosmetic, functional or sexual. Of the 55 women seeking labiaplasty, 10 met diagnostic criteria for body dysmorphic disorder. CONCLUSIONS: This is the first controlled study to describe some of the characteristics and motivations of women seeking labiaplasty. We identified a wide range of avoidance and safety-seeking behaviours, which occurred more frequently in the labiaplasty group than the control group. These could be used clinically as part of a psychological intervention for women seeking labiaplasty.

Sexual function in adult life following Passerini-Glazel feminizing genitoplasty in patients with congenital adrenal hyperplasia.

PURPOSE: We assessed external genitalia sensitivity and sexual function in adults with congenital adrenal hyperplasia who had undergone Passerini-Glazel feminizing genitoplasty as children, and compared them to a control group of healthy counterparts. MATERIALS AND METHODS: Inclusion criteria were congenital adrenal hyperplasia, Passerini-Glazel feminizing genitoplasty, adult age and penetrative vaginal intercourse. Thermal and vibratory sensitivity of the clitoris, vagina and labia minora were analyzed using the Genito Sensory Analyzer (Medoc Ltd., Minnetonka, Minnesota). Psychosexual outcome was assessed with the Beck Depression Inventory, Zung Self-Rating Anxiety Scale, Female Sexual Distress Scale and Female Sexual Function Index. Matched analyses were performed to compare outcomes in patients to controls (healthy medical students). All statistical tests were performed using SPSS®, version 18.0 RESULTS: A total of 12 patients (10%) entered the study. Thermal and vibratory clitoral sensitivity was significantly decreased in all patients compared to healthy controls (p <0.01). There was no difference in thermal or vibratory vaginal sensitivity between patients and controls. On the Female Sexual Distress Scale 11 patients (91.6%) and 11 controls (91.6%) described a stable satisfactory relationship. All patients reported active sexual desire, good arousal, adequate lubrication and orgasm. No significant difference in Female Sexual Function Index global score or single domain scores was observed between patients and controls. CONCLUSIONS: Although clitoral sensitivity in sexually active patients with congenital adrenal hyperplasia treated with Passerini-Glazel feminizing genitoplasty is significantly reduced compared to controls, sexual function in those patients is not statistically or clinically significantly different from their healthy counterparts. Finally, 1-stage Passerini-Glazel feminizing genitoplasty seems to allow normal adult sexual function.

New findings and concepts about the G-spot in normal and absent vagina: precautions possibly needed for preservation of the G-spot and sexuality during surgery.

AIM: The aim of this study was to extend the clinicohistological study to involve the whole normal and absent vagina for confirming the presence of the G-spot and its relation to the surrounding organs and sexuality and to identify certain precautions for its preservation during surgery. MATERIAL AND METHODS: This study was a descriptive randomized prospective study conducted at Kasr El Aini School of Medicine, Cairo University, Egypt. The G-spot was examined in 1500 women, 500 of them having vaginal and vulval surgery done for gynecological reasons. The G-spot was examined for its clinical and histological features and for determining the effect of surgery on its state and function. RESULTS: The G-spot was found to be present in all women. It was a localized spot in 58% and diffuse in 42% of cases. Associated ejaculation was reported in all cases of the localized type and in 24.5% of the diffuse types. Clinical examination was found to be associated with certain local response in 52.7% of the local types. The G-spot was also found to be connected to the hymen in 100%, the urethra in 52.7%, the vulva in 82.2% and the cervix in 10.8% of cases. The mean of the sex scores and sexuality were significantly decreased in surgery involving the G-spot area. Recorded figures were 93.6 ± 3.4 and 88.2 ± 3.3 before and after surgery, respectively. The corresponding figures in the cases having a general spot were 86.4 ± 4.4 and 84.5 ± 2.4, respectively. The G-spot was found in cases of absent vagina to be localized in 59%, generalized in 28.2% and absent in 12.8% of cases. CONCLUSIONS: The G-spot is actually present in all women. It is originally related to the lower urinary tract and it is connected to different parts of the genital tract. It may be localized or generalized. Its integrity is essential for obtaining normal physiological sexuality. Surgery may affect the integrity of the G-spot, so surgical precautions must be carried out to maintain the integrity of this spot and the patient's sexuality.

Genitofemoral and perineal neuralgia after transobturator midurethral sling.

BACKGROUND: Midurethral slings successfully treat stress urinary incontinence through a minimally invasive vaginal approach. Postoperative pain related to sling placement can occur and poses both diagnostic and treatment dilemmas. CASE: Four years after transobturator midurethral sling placement, the patient presented with complaints of left labial pain and dyspareunia since surgery. Using sensory mapping and a nerve stimulator, the problem was identified in the distribution of the genitofemoral nerve. Conservative therapy with a centrally acting neuromodulatory drug and nerve block relieved the pain. CONCLUSION: Postsling neuralgia diagnosis using sensory mapping and a nerve stimulator aids in indentifying the nerve involved and in successful conservative treatment with a nerve block.

KIT pathway alterations in mucosal melanomas of the vulva and other sites.

PURPOSE: A significant proportion of mucosal melanomas contain alterations in KIT. The aim of this study was to characterize the pattern of KIT, NRAS, and BRAF mutations in mucosal melanomas at specific sites and to assess activation of the KIT downstream RAF/MEK/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT pathways in mucosal melanoma specimens. EXPERIMENTAL DESIGN: Seventy-one primary mucosal melanomas from various sites were studied. Mutation analysis was done by DNA sequencing. Expression of KIT, phosphorylated (p)-ERK, and p-AKT was evaluated by immunohistochemistry. RESULTS: KIT mutations were detected in 35% (8 of 23) of vulvar, 9% (2 of 22) of anorectal, 7% (1 of 14) of nasal cavity, and 20% (1 of 5) of penile melanomas. No KIT mutations were found in 7 vaginal melanomas. The difference in KIT mutation frequency between vulvar and nonvulvar cases was statistically significant (P = 0.014). The overall frequencies of NRAS and BRAF mutations were 10% and 6%, respectively. Notably, vaginal melanomas showed a NRAS mutation rate of 43%. KIT gene amplification (≥4 copies), as assessed by quantitative real-time PCR, was observed in 19% of cases. KIT expression was associated with KIT mutation status (P < 0.001) and was more common in vulvar than nonvulvar tumors (P = 0.016). Expression of p-ERK and p-AKT was observed in 42% and 59% of tumors, respectively, and occurred irrespective of KIT/NRAS/BRAF mutation status. NRAS mutation was associated with worse overall survival in univariate analysis. CONCLUSIONS: Results show that KIT mutations are more common in vulvar melanomas than other types of mucosal melanomas and that both the RAF/MEK/ERK and PI3K/AKT pathways are activated in mucosal melanoma specimens.