BRAF and KIT somatic mutations are present in amelanotic melanoma.

The genotypic profile of rare amelanotic melanomas (AMs) has been poorly investigated, thus preventing either an accurate identification as a distinctive melanoma subtype or therapy stratification. Here, we investigated the presence of the BRAF(V600E) mutation by real-time quantitative PCR and KIT mutations (exons 11 and 17) by sequencing analysis in 33 AMs. AMs included 'truly' amelanotic lesions (n = 19), with no melanin pigmentation upon dermoscopic inspection and hypomelanotic lesions (n = 14), by definition partially pigmented lesions showing a melanin pigmentation area of less than 25% of the total surface area. The frequency of the BRAF(V600E) mutation was 70.3% in the 33 cases, a percentage that increased to 89% when only the subgroup of thin melanomas (≤ 1 mm in thickness, n = 9) was considered. KIT mutations were found in 12.1% of AMs, all of which developed in nonacral sites. The identification of a relatively high frequency of BRAF(V600E) and KIT mutations in AMs may have important consequences for implementation of the novel targeted therapies now available to treat this life-threatening disease.

Histological evidence of urethral involvement in male patients with genital lichen sclerosus: a preliminary report.

PURPOSE: Using pathological examination we evaluated the involvement of lichen sclerosus in urethral strictures in men. MATERIALS AND METHODS: We performed an observational, descriptive, retrospective study of patients treated for genital lichen sclerosus who had at least 1 biopsy positive for lichen sclerosus. Study exclusion criteria were malignant penile lesions, incomplete data on personal charts and biopsies negative for lichen sclerosus. Preoperative evaluation included clinical history, physical examination, urine culture, post-void residual urine measurement, uroflowmetry and urethrography. Biopsies were taken from the foreskin, penile skin, glans, urethral meatus, mucosa of the navicularis, and penile and bulbar urethra to confirm the lichen sclerosus diagnosis and spread of the disease through the urethra. Patients were classified into 5 groups by surgical procedure. RESULTS: Included in the study were 99 patients with a median age of 46 years who were diagnosed with genital lichen sclerosus. Of 274 biopsies 234 (85.4%) were positive for lichen sclerosus. Group 1 included 39 patients who underwent circumcision, group 2 included 15 who underwent meatotomy, group 3 included 15 who underwent navicularis urethroplasty, group 4 included 17 who underwent penile urethroplasty and group 5 included 13 who underwent perineal urethrostomy. Lichen sclerosus was documented by histology in the meatus in 91.5% of cases, in the navicularis in 84.4% and in the penile urethra in 70.6%. All biopsies from the bulbar urethra were negative. CONCLUSIONS: Involvement of lichen sclerosus through the navicularis and penile urethra was documented. No sign of lichen sclerosus was found in the bulbar urethra.

Human papillomavirus infection and risk factors in a cohort of Tuscan women aged 18-24: results at recruitment.

BACKGROUND: There is conclusive evidence that human papillomavirus (HPV) infections of the cervix are a necessary cause of cervical cancer. In Italy there are consistent data of HPV prevalence in women aged 25 - 64 years, but there is limited data for younger women. The objective of this on-going 3-year prospective cohort study is to investigate the prevalence, acquisition, clearance and persistence of HPV infections in young Tuscan women and the risk factors correlated with such events. METHODS: One thousand and sixty-six women aged between 18 and 24 years were enrolled and received an initial HPV test. They were asked to return to the clinic over the study period for further tests every 12 months, if their HPV HR result was negative, or every 6 months, if positive. Additionally, women with an HPV positive result were given a cytological examination and if the cytological diagnosis was ASC-US or more severe, only women with HPV HR, were referred for colposcopy. RESULTS: We present here data for the enrollment phase of the study. At baseline, within the study sample, just under 30% of women were infected by HPV and 19.3% of women were infected with oncogenic types. A relationship was highlighted between HPV infection, number of sexual partners (in particularly in the last 3 years) and the lifetime number of partner's partners. Condom use showed a slight protective effect in univariate analysis but these data were not statistically significant in multivariate analysis. The association between HPV infection and demographic and behavioural variables were tested by crude odds ratio (OR). Multivariate logistic regression was applied to compute the adjusted odds ratios. CONCLUSIONS: The prevalence of oncogenic HPV types was high in young Tuscan women. The 3-year follow-up of this cohort may provide a better understanding of the processes of acquisition, clearance and persistence of infection and the correlated risk factors.

Lichen sclerosus of the male genitalia and urethra: surgical options and results in a multicenter international experience with 215 patients.

BACKGROUND: Surgical options in male patients with genital lichen sclerosus (LS) involving the anterior urethra still represent a challenging issue. OBJECTIVE: To review the outcome of surgical treatment in patients with genital and urethral LS. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, international, retrospective, observational descriptive study performed in two specialized centers. Two hundred fifteen male patients underwent surgery for histologically proven genital LS involving the foreskin and/or the anterior urethra. INTERVENTION: Circumcision (34 cases), meatotomy (15 cases), circumcision and meatotomy (8 cases), one-stage penile oral mucosal graft urethroplasty (8 cases), two-stage penile oral mucosal graft urethroplasty (15 cases), one-stage bulbar oral mucosal graft urethroplasty (88 cases), and definitive perineal urethrostomy (47 cases). MEASUREMENTS: Primary outcome was considered a failure when any postoperative instrumentation was needed, including dilation, or when recurrence was diagnosed. RESULTS AND LIMITATIONS: The average follow-up was 56 mo (range: 12-170 mo). Circumcision showed 100% success rate with no recurrence of the disease; meatotomy, 80% success rate; circumcision and meatotomy, 100% success rate; one-stage penile oral mucosal graft urethroplasty, 100% success rate; two-stage penile oral mucosal graft urethroplasty, 73% success rate; one-stage bulbar oral mucosal graft urethroplasty, 91% success rate; and definitive perineal urethrostomy, 72% success rate. Limitations include short follow-up for recording neoplastic degeneration and no instrument to investigate quality of life. CONCLUSIONS: Patients with LS disease restricted to the foreskin and/or external urinary meatus showed a high surgery success rate. In patients with penile urethral strictures or panurethral strictures, the use of one-stage oral graft urethroplasty showed greater success than the staged procedures.

Resurfacing and reconstruction of the glans penis.

OBJECTIVES: To describe the techniques and results of surgical reconstruction of glans penis lesions. METHODS: Seventeen patients (mean age: 53.2 yr) were treated by resurfacing or reconstruction of the glans penis for benign, premalignant and malignant penile lesions. The aetiology of the lesions was one Zoon's balanitis, four lichen sclerosus, one carcinoma in situ, five squamous cell carcinomas, and six squamous cell carcinomas associated with lichen sclerosus. Five cases were treated by glans skinning and resurfacing; five cases by glans amputation and reconstruction of the neoglans, and seven cases by partial penile amputation and reconstruction of the neoglans. Glans resurfacing and reconstruction were performed with the use of a skin graft harvested from the thigh. RESULTS: The mean follow-up was 32 mo. All patients were free of local premalignant/malignant recurrence. Patients who underwent glans resurfacing reported glandular sensory restoration and complete sexual ability. Patients who underwent glansectomy or partial penectomy with neoglans reconstruction maintained sexual function and activity, although sensitivity was reduced as a consequence of glans/penile amputation. CONCLUSIONS: In selected cases of benign, premalignant or malignant penile lesions, glans resurfacing or reconstruction can ensure a normal appearing and functional penis, without jeopardizing cancer control.

Digital images for interobserver variability comparison in cervicovaginal cytology.

OBJECTIVE: To assess whether digital images can be useful in evaluating interobserver variability in cervical-vaginal cytology. STUDY DESIGN: In phase 1 of the study, to measure interobserver variability, a set of 160 digital images was submitted to 192 cytologists with experience ranging from 2 to > 30 years. The set was preceded by two days of immersion in lessons and practical exercises with digital images. In phase 2, to compare different procedures of interobserver variability, two different sets of slides and one set of digital images were used. RESULTS: In phase 1, kappa and weighted kappa w values computed against both the consensus and the target diagnosis showed good agreement, with few exceptions. In phase 2, the consensus and target diagnoses obtained on the slide sets and digital set were compared. Mean k and kw values obtained with the digital images in phase 2 were significantly lower as compared to those in phase 1. CONCLUSION: A set of digital images can be a useful tool for evaluating and improving interobserver reproducibility. A two-day course on digital images could be an ideal modality for introducing this new technology.