Genital and extragenital oncological risk in women with vulvar lichen sclerosus: A multi-center Italian study.

Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. METHODS: A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. RESULTS: Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. CONCLUSIONS: Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.

SIIV position paper: clinical approach to vulval diseases. Need for quality standards.

This paper summarizes the position of the Italian Society of Vulvology on the clinical approach to vulval disease. A thorough history (general medical, gynaecological, and vulval history) is essential for a successful and fruitful vulvological examination. Characteristics of pruritus (itch) and pain, that are the two main vulval symptoms, should be collected and reported with precision, according to duration, temporal course, location, provocation, and intensity. Physical examination must consider both the general condition of the patient and the specific vulval region, that must be examined following a standardized methodology. The physical examination of the vulva is carried out with naked eye and adequate natural or halogen lighting. The subsequent use of instrumental magnification can be considered on particular parts of skin/mucosa, already highlighted with the first inspection. Also, palpation is essential, allowing to appreciate physical features of vulval lesions: consistency, surface, soreness, adherence to underlying plans. Finally, the five-step approach of the International Society for the Study of Vulvo-vaginal Disease about Terminology and Classification of Vulvar Dermatological Disorders (2012) is summarized. A vulval biopsy may be useful in the following situations: when clinical diagnosis is uncertain, lesion not responding to treatment; histologic confirmation for a clinical diagnosis and exclusion or confirmation of a suspected neoplastic intraepithelial or invasive pathology.

Women With Primary Sjögren Syndrome and With Non-Sjögren Sicca Syndrome Show Similar Vulvar Histopathologic and Immunohistochemical Changes.

The goal of this study was to evaluate the characteristics and the prevalence of histopathologic and immunohistochemical changes in vulvar biopsies, in women with Primary Sjögren Syndrome (pSS) and non-Sjögren Sicca Syndrome (nS-SS). Twenty-one women with pSS and 11 with nS-SS (investigated by xerophtalmia and xerostomia tests, biopsy of minor salivary glands, gynecological history, and gynecologic symptoms score) underwent vulvar biopsies, evaluated for histopathologic and immunohistochemicalchanges, and compared with those obtained from 26 patients with lichen sclerosus. An inflammatory infiltrate was present in 31/32 biopsies (96.9%); biopsies from pSS patients showed a mild infiltrate in 10 cases and a moderate infiltrate in 11 cases; and patients with nS-SS had a mild infiltrate in 8 biopsies and moderate infiltrate in the other 2 biopsies. By immunohistochemistry, the infiltrate was composed predominantly of T lymphocytes (CD3), CD20 B cells were sparse and mean CD4:CD8 T-cell ratio was 1.5. No differences were observed between the grading of the inflammatory infiltrate in nS-SS and pSS; no correlation was shown between vulvar inflammatory infiltrate score (mild or moderate) and salivary glands inflammatory score. No differences were found in gynecologic symptoms, as well as in clinical and demographical characteristics between patients with mild and those with moderate vulvar inflammatory score. A higher prevalence of moderate inflammatory infiltrate was observed in biopsies from women with lichen sclerosus than in pSS and nS-SS patients (61.5% vs. 27.5%, P=0.02). Women with pSS and nS-SS show a high and similar prevalence of vulvar inflammatory infiltrate. A gynecologic evaluation is needed both in pSS and nS-SS to assess genital involvement and, eventually, to address a therapy targeted to genital symptoms.

Two-team simultaneous total radical vulvectomy and inguino-femoral lymphadenectomy via separate incisions for locally advanced (FIGO stages IB ≥ 4 cm-III) squamous vulvar cancer.

AIM: To describe the feasibility, safety, and oncological outcomes of a modified triple-incision total radical vulvectomy and inguino-femoral lymphadenectomy in patients with locally advanced squamous vulvar cancer. PATIENTS AND METHODS: A modified triple-incision technique performed by two surgical teams operating simultaneously under regional anesthesia was performed on a consecutive series of 57 patients with Fédération Internationale de Gynécologie Ostétrique (FIGO) stages IB ≥ 4 cm to III squamous vulvar cancer. Adjuvant radiation therapy was delivered according to margin status and groin involvement. Surgical outcomes and follow-up data were retrospectively analyzed. RESULTS: The mean age of patients was 75.5 ± 10.7 years and 54 (94.7%) had at least one comorbidity. Fifteen (26.3%) had disease of clinical FIGO stage I ≥ 4 cm, 7 (12.3%) had stage II, and 35 (61.4%) had a stage III. All surgical procedures were completed as planned. The mean surgical duration was 108 ± 37 min. Major intraoperative complications were observed in two cases (3.5%). Twenty-one (36.8%) patients received adjuvant radiation therapy. During a mean follow-up of 51.6 ± 50.5 months, 29 (50.9%) patients developed local, regional or distant recurrence. The disease-free survival was 39.5 ± 20.9 months. Nineteen (33.3%) patients died of primary disease. Overall survival for the entire cohort was 65.4%, with 3-year and 5-year overall survival of 60.5% and 48.6%, respectively. CONCLUSION: Our results seem to reveal that the procedure is safe, with surgical and oncological outcomes comparable to classic sequential triple-incision technique. The shortening of surgical duration along with the use of regional anesthesia can have significant advantages for perioperative care, reducing the global burden of treatment and increasing the number of patients eligible for therapeutic surgery.

Vulvar paget disease: a large single-centre experience on clinical presentation, surgical treatment, and long-term outcomes.

OBJECTIVE: Our aim was to add information to the current literature on vulvar Paget disease by reviewing a consistent number of patients who have been all diagnosed, treated, and followed up by the same group of physicians at a single medical institution. METHODS: Clinical, surgical, histological, and follow-up data of 34 patients (mean [SD] age at diagnosis = 68.7 [10.1] years) with vulvar Paget disease were reviewed during a 27-year period. RESULTS: Primary symptoms were itching (76.5%) and burning (58.8%). Clinical manifestations were present for a mean (SD) of 17.8 (7.2) months before the diagnosis was made. Multifocal lesions were observed in 17 patients (50%) and were associated with a delay in diagnosis exceeding 12 months (p = .03). Of the patients, 10 (29.4%) presented a history of malignancy in other sites. Surgery with various extent of resection was performed as primary treatment in all patients. Definitive histological examination revealed positive surgical margins in 15 cases (44.1%), stromal invasion in 4 (11.7%), and associated adenocarcinoma in 2 (5.9%). Of the patients, 6 (17.6%) underwent reconstructive technique at their primary surgery or radicalization. During a mean (SD) follow-up of 76.9 (51.3) months, 15 patients (44.1%) experienced local recurrence (1 recurrence in 29.4%, 2 recurrences in 5.9%, and 3 recurrences in 8.8%). First recurrence appeared after a mean (SD) time of 45.7 (25.1) months and was associated with multifocal lesions (p = 0.005) and surgical margins involvement (p = 0.03). One patient (2.6%) died of the disease. CONCLUSIONS: Vulvar Paget disease is a chronic disease with high recurrence rate and low mortality. Early diagnosis, minimal surgery with free margins, and long-term follow-up are the cornerstones of treatment.

Dermoscopic features of mucosal melanosis.

BACKGROUND: Melanosis (lentiginosis, labial melanotic macula) is a benign pigmented lesion of mucosa characterized by pigmentation of basal keratinocytes with melanocytic normal or slightly increased in number. Melanosis, particularly when occurring on genitalia, can clinically mimic mucosal melanoma thus creating concern in both the patient and the physician. OBJECTIVE: In this study dermoscopic features from a series of clinically equivocal (n=11) or clinically typical (n=10) mucosal melanosis were analyzed. METHODS: All the women consecutively seen at the Vulva Clinic of the Department of Obstetrics and Gynecology, University of Florence, Italy, from May 1, 2002 to June 30, 2002, were examined. RESULTS: Three major dermoscopic patterns were identified: (1) a "structureless" pattern, predominantly found in clinically equivocal vulvar melanosis, with a blue hue, associated with the presence of melanophages in the upper dermis, present in the majority of these lesions; (2) a "parallel pattern," often found in clinically typical melanotyc macules of the lips and penis; and (3) a "reticular-like" pattern associated with clinically equivocal melanosis occurring at peculiar sites such as the areola (all the three cases occurred at that site) or, rarely, on the lip. CONCLUSIONS: Dermoscopy can play a role in the noninvasive classification of mucosal melanosis. The risk of misclassification with melanoma is probably dependent on dermoscopy pattern shown by the lesion. Prospective studies including early melanomas are needed to establish diagnostic performance of dermoscopy in pigmented lesions of the mucosa.

Topical mometasone furoate for vulvar lichen sclerosus.

OBJECTIVE: To assess the efficacy and safety of treating vulvar lichen sclerosus with mometasone furoate, a synthetic analogue of beclomethasone. STUDY DESIGN: Thirty-one consecutive patients with biopsy-proven vulvar lichen sclerosus (LS) seen at the Florence Vulvar Clinic were entered into the study. Each subject's symptoms and the gross appearance of the lesions were recorded using a severity score according to the authors' previous studies. The patients were treated with a regimen of 0.1% mometasone furoate cream applications to the affected areas once daily for 4 weeks and then twice weekly for 8 weeks. After 12 weeks of treatment, the subjects were asked to rate the changes in their symptoms and were reevaluated by the same examiner for the gross appearance of the lesions. In every patient the before/after treatment total severity scores were compared using Wilcoxon's signed-rank test for statistical significance. RESULTS: With mometasone furoate all the patients had a significant improvement (P < .001) in the gross aspects of the disease and a very dramatic decrease in symptoms (P < .001), with nearly all the subjects having complete symptomatic remission. Compliance was excellent, and no side effects were observed. CONCLUSION: The improved risk/benefit ratio of mometasone furoate may minimize the possible long-term side effects expected when using a very potent topical steroid. Therefore, momentasone furoate cream may be an alternative to clobetasol propionate for treatment of vulvar LS, with similar efficacy but higher levels of safety and tolerability.

Vulvar carcinoma associated with lichen sclerosus. Experience at the Florence, Italy, Vulvar Clinic.

OBJECTIVE: To compare demographic and clinical characteristics of patients with lichen sclerosus (LS)-associated squamous cell carcinoma (SCC) of the vulva with those of patients with tumors not histologically associated with LS in a series of patients with vulvar SCC not HPV correlated. STUDY DESIGN: We retrospectively reviewed histologic specimens and clinical files of all vulvar SCCs referred to the Vulvar Clinic, University of Florence, Florence, Italy, since 1990. RESULTS: Twenty-five out of the 72 cases in this study (34.7%) were LS associated. Among these cases, 8 (32%) were diagnosed with LS before occurrence of the cancer and received treatment for the disease. In 17 cases the diagnosis of LS was simultaneous with that of SCC; in 13 cases the diagnosis was achieved by clinical examination and confirmed afterwards histologically. In 4 cases this was confirmed only by means of histologic examination. The shared profile of patients with LS-associated vulvar SCC was a subject (mean age, 72 years) seldom with a past medical history of vitiligo (16% of cases), with invasive cancer (92% of cases), clinically characterized by an exophitic tumor (73%), seldom ulcerated (18%) or showing hyperkeratosis (9%). Labia majora (32%), labia minora (27%) and vestibule (23%) were the most frequently involved sites. In most cases (80%) the cancer was limited to 1/3 of the vulvar region. An itch was the most frequent symptom. However, for all of these variables, no overall statistically significant difference was found with patients who had SCCs not associated with LS. CONCLUSION: The experience of the Vulvar Clinic, University of Florence, confirms the suggested role of LS as a possible precursor of vulvar carcinoma since 32% of our cases not HPV related were LS associated. We demonstrated that the profile of patients with LS-associated cancer does not differ from that of patients with cancer not associated with LS, excluding HPV-related cases. The existence of accessory conditions, probably needed to promote the progression from LS to cancer in a minority of subjects remains to be established.