Performance of Different Follow-Up Strategies and Genotype-Based Recurrence Risk After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

OBJECTIVE: Our aim was to evaluate the performance of different follow-up strategies after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3, including human papillomavirus (HPV) detection, cytology, or colposcopy, as well as their combinations. Additionally, we compared the influence of the persistence of HPV 16/18 versus that of other high-risk HPV genotypes (HR-HPV) in the recurrence risk. METHODS: Retrospective register-based study, including women who had an excision of the transformation zone for CIN2 or CIN3 at our institution, between January 2011 and December 2022. The outcome assessed was histopathological recurrence/persistence of CIN2 or worse. RESULTS: Of the 721 women included, 6.8% (49/721) had recurrence/persistence. The sensitivity, specificity, and positive and negative predictive values of the HPV test were 97.4%, 80%, 22.3%, and 99.8%, respectively, whereas for cotesting (HR-HPV and cytology), 86.8%, 90.1%, 34.4%, and 99.1%, respectively. The referral rates for colposcopy were 24.3% and 14.2%, respectively. The sensitivity of colposcopy was low (40.0%).Women who were initially positive for non-16/18 genotypes at baseline who became HPV16/18 positive during follow-up, had a statistically significant increased risk of CIN2 or worse, compared with those who tested positive only for other HR-HPV genotypes during both stages (hazard ratio = 4.98; 95% CI = 1.66-14.91). CONCLUSIONS: Human papillomavirus testing is the best strategy for follow-up after treatment of cervical HSIL. The addition of cytology triage decreases by more than 40% the referrals for colposcopy, without significantly missing cases of recurrence/persistence. Human papillomavirus 16/18 in the follow-up, regardless of being previously positive, is associated with higher risk of recurrence/persistence of HSIL.

Differentiated vulvar intraepithelial neoplasia long-term follow up and prognostic factors: An analysis of a large historical cohort.

INTRODUCTION: Differentiated vulvar intraepithelial neoplasia (dVIN) is a high-risk preinvasive vulvar lesion and precursor of human papillomavirus-independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN-VSCC) at first diagnosis. MATERIAL AND METHODS: A historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan-Meier method and log-rank test were used to estimate cancer risk or recurrent cancer risk differences and uni- and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN-VSCC. RESULTS: Seventy-six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN-VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5-128.0 months). VSCC recurrence absolute risk in treated dVIN-VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5-94.8 months). At uni- and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN-VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN-VSCC patients on both uni- and multivariate regression analyses. CONCLUSIONS: Patients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long-term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.

Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: A multicentric Italian study.

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high-grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin-fixed paraffin-embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2 and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2 and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2 and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2 and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine-valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia.

The International Society for the Study of Vulvovaginal Disease (ISSVD) Vulvar Awareness Day Campaign: Knowledge of Vulvovaginal Diseases Among Italian Obstetrics and Gynecology Residents.

OBJECTIVES: The objective of this study is to investigate vulvovaginal disease (VVD) awareness in Italian obstetrics and gynecology (Ob/Gyn) residents. MATERIALS AND METHODS: A 25-question survey on VVD basic knowledge (17 questions) and willingness to improve it (8 questions) was distributed through Ob/Gyn resident online group chats, from different Italian Universities in January 2023. A total number of 250 residents were invited to participate; 124 responses were obtained (response rate: 50%). Data were collected and analyzed using descriptive statistics through REDCap. RESULTS: Overall, 87 of the 124 respondents (70%) fully completed the questionnaire and represented the study group. Residents were distributed among years of residency: 15% first year, 31% second year, 23% third year, 11% fourth year, and 20% fifth year. Most (60%) never attended a VVD clinic during residency, with an increasing percentage of attendance in later residency years (15% at first year vs 65% at fifth).Participants reported low knowledge of vulvar precancerous lesions and vulvoscopy but better knowledge of vaginitis, vulvar self-examination, and lichen sclerosus. Of the respondents, 50% were not satisfied with the education provided during residency, and more than 60% lacked confidence in managing VVD.All participants expressed a strong desire to improve their knowledge and skills, with 100% agreeing that every gynecologist should know the "basics" and 98% wanting to improve their knowledge through webinars (45%), lessons (34%), newsletters, and videos (19%). CONCLUSION: Our findings indicate a significant need to improve VVD knowledge among Italian Ob/Gyn residents. Further efforts are necessary to provide information about VVD and comprehensive training programs in Italian Universities.

Uterine smooth muscle tumors: a multicenter, retrospective, comparative study of clinical and ultrasound features.

OBJECTIVE: To evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types. METHODS: This was a retrospective, multicenter study that included 285 patients diagnosed with uterine smooth muscle tumors (50 leiomyosarcomas, 35 smooth muscle tumors of uncertain malignant potential, and 200 leiomyomas). The patients were divided into three groups based on the histological type of their tumors, and the groups were compared according to the variables collected. RESULTS: Leiomyosarcomas were more common in older and post-menopausal women. Compared with leiomyomas, smooth muscle tumors of uncertain malignant potential and leiomyosarcomas had similar ultrasound features such as absence of normal myometrium, multilocular appearance, hyper-echogenicity in case of uniform echogenicity, absence of posterior shadows, echogenic areas, and hyperechoic rim. Leiomyosarcomas were larger, had more cystic areas, and were associated with a higher prevalence of pelvic free fluid. Smooth muscle tumors of uncertain malignant potential were characterized by a higher frequency of International Federation of Gynecology and Obstetrics (FIGO) type 6-7, the absence of internal shadows, and, in the case of cystic area, the presence of a regular internal wall. Tumor outline varied among the three histological types. A color score of 1 was typical of leiomyoma, a color score 2 was mainly observed in leiomyomas and smooth muscle tumors of uncertain malignant potential, a color score 3 did not differ among the tumors, while a color of score 4 was related to leiomyosarcomas. When combining color scores 3 and 4, leiomyosarcomas and smooth muscle tumors of uncertain malignant potential showed a high percentage of both circumferential and intra-lesional vascularization. A cooked appearance was not statistically different among the tumors. CONCLUSIONS: Based on our findings, specific ultrasonographic features as well as age and menopausal status are associated with different uterine smooth muscle tumor types. Integration of these data can help the pre-operative assessment of these lesions for proper management.

Recent advances in treating female genital human papillomavirus related neoplasms with topical imiquimod.

Human papillomavirus (HPV) encompasses a group of viruses that infect the skin and mucous membranes. In the presence of certain factors, persistent infection with high-risk HPVs can trigger a process of neoplastic transformation. Imiquimod is a topical agent that acts as a Toll-like receptor 7/8 agonist, stimulating the innate and adaptive immune system to exert antitumor and antiviral effects. It has been approved for the treatment of various skin conditions, however, its efficacy and safety in the management of HPV-related-neoplasms of the lower genital tract, such as vulvar, vaginal, and cervical neoplasia, are still under investigation. This review summarizes the current evidence on the use of imiquimod for the treatment of HPV-induced lesions of the female lower genital tract, focusing on its indications, mechanisms of action, outcomes, and predictors of response.

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.

Human papillomavirus infection in women undergoing in-vitro fertilization: effects on embryo development kinetics and live birth rate.

BACKGROUD: Several studies showed that human papillomavirus (HPV) affects male fertility, but its impact on female fertility and in vitro fertilization (IVF) outcome is not yet clear. METHODS: Objective of this observational, prospective, cohort study was to evaluate the prevalence of HPV infection in women candidate to IVF, and the effects of HPV infection on the kinetic of embryonic development and on IVF outcome. A total number of 457 women candidate to IVF were submitted to HR-HPV test; among them, 326 underwent their first IVF cycle and were included in the analysis on IVF results. RESULTS: 8.9% of women candidate to IVF were HPV-positive, HPV16 being the most prevalent genotype. Among the infertility causes, endometriosis was significantly more frequent in HPV-positive than in negative women (31.6% vs. 10.1%; p < 0.01). Granulosa and endometrial cells resulted HPV-positive in 61% and 48% of the women having HPV-positive cervical swab, respectively. Comparing HPV-positive and negative women at their first IVF cycle, no significant difference was observed in the responsiveness to controlled ovarian stimulation (COS) in terms of number and maturity of retrieved oocytes, and of fertilization rate. The mean morphological embryo score was comparable in the two groups; embryos of HPV-positive women showed a quicker development in the early stages, with a significantly shorter interval between the appearance of pronuclei and their fusion. In the following days, embryo kinetic was comparable in the two groups until the early blastocyst stage, when embryos of HPV-positive women became significantly slower than those of HPV-negative women. Overall, these differences did not affect live birth rate/started cycle, that was comparable in HPV-positive and negative women (22.2 and 28.1%, respectively). CONCLUSIONS: (a) the prevalence of HPV infection in women candidate to IVF is similar to that observed in the general female population of the same age range; (b) HPV infection migrates along the female genital apparatus, involving also the endometrium and the ovary, and perhaps participates in the genesis of pelvic endometriosis; (c) HPV slightly affects the developmental kinetic of in vitro-produced embryos, but does not exert an effect on live birth rate.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia.

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

HPV Tests Comparison in the Detection and Follow-Up after Surgical Treatment of CIN2+ Lesions.

BACKGROUND: HPV tests differ for technology, targets, and information on genotyping of high risk (HR) HPV. In this study, we evaluated the performance of 6 HPV DNA tests and one mRNA test in the detection of cervical intraepithelial lesions (CIN) and as a test-of-cure in the follow-up after surgical conservative treatment. METHODS: One hundred seventy-two women referred to the European Institute of Oncology, Milan, for surgical treatment of pre-neoplastic cervical lesions, were enrolled in this study (IEO S544) from January 2011 to June 2015. For all women, a cervical sample was taken before treatment (baseline) and at the first follow-up visit (range 3 to 9 months): on these samples Qiagen Hybrid Capture 2 (HC2), Roche Linear Array HPV Test (Linear Array), Roche Cobas 4800 HPV test (Cobas), Abbott RealTime High Risk HPV test (RT), BD Onclarity HPV assay (Onclarity), Seegene Anyplex II HPV HR Detection (Anyplex), and Hologic Aptima HPV Assay (Aptima) histology and cytology were performed at baseline, and the same tests and cytology were performed at follow-up. RESULTS: At baseline 158/172 (92%), histologies were CIN2+, and 150/172 (87%) women were recruited at follow-up. Assuming HC2 as a comparator, the concordance of HPV tests ranges from 91% to 95% at baseline and from 76% to 100% at follow-up (PABAK ranging from 0.81 to 0.90 at baseline and PABAK ranging from 0.53 to 1 at follow-up). All HPV showed a very good sensitivity in CIN2+ detection at baseline, more than 92%, and a very good specificity at follow-up, more than 89%. CONCLUSIONS: HPV tests showed a good concordance with HC2 and a very good and comparable sensitivity in CIN2+ detection. Hence, an HPV test represents a valid option as test-of-cure in order to monitor patients treated for CIN2+ lesions during follow-up.

Clinical and Histopathological Predictors of Recurrence in Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Multicenter Retrospective Cohort Study of Tertiary Centers.

BACKGROUND: The term uterine smooth muscle tumor of uncertain malignant potential (STUMP) indicates a rare, equivocal entity between benign leiomyomas and leiomyosarcomas. In the present study, we evaluated a comprehensive range of clinical, surgical, and pathological features in a large multicenter series of patients with STUMP to identify risk factors for recurrence. METHODS: This is a retrospective study performed by collecting consecutive cases diagnosed between January 2000 and December 2020 in five tertiary centers. Associations between STUMP recurrence and clinicopathological characteristics as well as surgical treatment modality were investigated. RESULTS: Eighty-seven patients affected by STUMP were considered. Of them, 18 cases (20.7%) recurred: 11 as leiomyosarcoma (LMS) and 7 as STUMP. The mean time to recurrence was 79 months. We found that fragmentation/morcellation, epithelioid features, high mitotic count, Ki-67 value > 20%, progesterone receptor (PR) < 83%, and p16 diffuse expression were associated with higher risk of recurrence and shorter recurrence-free survival (RFS). Furthermore, morcellation/fragmentation and mitotic count remained independent risk factors for recurrence and shorter RFS after multivariate analysis, while the presence of epithelioid features was an independent risk factor for recurrence only. CONCLUSIONS: Our results suggest that morcellation is associated with risk of recurrence and shorter RFS, thus it should be avoided if a STUMP is suspected preoperatively. Epithelioid features, high proliferation activity, low PR expression, and diffuse p16 expression are also unfavorable prognostic factors, so patients presenting these features should be closely followed up.

Vaginal Leptothrix: An Innocent Bystander?

Leptothrix are long bacteria of rare occurrence; although these bacteria have been implicated in causing vaginal symptoms identical to candidiasis, studies on prevalence and effect on overall vaginal health are lacking. In this study, we evaluated data of women referred to a private clinic for treating vulvovaginal symptoms (n = 1847) and reassessed data of our previous and ongoing studies (n = 1773). The overall rate of leptothrix was 2.8% (102/3620), and the mean age of affected women was 38.8 ± 10.65 years (range 18-76). The majority of the women with leptothrix had normal vaginal flora (63.7% [65/102]). Leptothrix was associated with a higher risk of candidiasis (relative risk (RR) 1.90, 95% confidence interval (CI) 1.1600-3.1013; p = 0.010) and a lower risk of bacterial vaginosis (RR 0.55, 95% CI, 0.3221-0.9398; p = 0.029) and cytolytic vaginosis (RR 0.11, 95% CI, 0.0294-0.4643; p = 0.002). No cases of trichomoniasis were observed. Human immunodeficiency virus infection increased the risk of leptothrix (RR 3.0, 95% CI, 1.6335-5.7245; p = 0.000). Among the women evaluated for vulvovaginal symptoms, 2.4% (45/1847) had leptothrix, and in 26.7% (12/45), leptothrix was considered the causative entity. This study suggests that leptothrix occurrence is rare; it remains unresolved if it can be a cause of vulvar symptoms.

Low-Grade Uterine Endometrial Stromal Sarcoma: Prognostic Analysis of Clinico-Pathological Characteristics, Surgical Management, and Adjuvant Treatments. Experience From Two Referral Centers.

Objective: Low-grade uterine endometrial stromal sarcoma (LG-ESS) is a rare tumor characterized by an overall good survival but showing a indolent behavior and a variable risk of recurrence. There is no clear consensus on the optimal management of these tumors and no prognostic or predictive factors have been established. With this study, we evaluated the prognostic relevance of several clinical, surgical, and pathological features in patients affected by LG-ESS to identify risk factors associated with recurrence. Methods: We retrospectively analyzed 52 LG-ESS cases, treated from January 1st, 1994, to May 31st, 2020, in two referral centers. The relationship between recurrence and clinicopathological characteristics as well as surgical treatment was investigated. Risk of recurrence and disease-free survival (DFS) were estimated by Cox regression and the Kaplan-Meier analysis, respectively. Results: Of 52 patients with LG-ESS, 8 experienced recurrence (15%). The median follow-up was 100 months (SD ± 96, range: 15-336). By univariate analysis, fragmentation/morcellation, tumor size, FIGO stage, higher mitotic count, presence of necrosis, and lymphovascular space invasion (LSVI) resulted associated with a poorer outcome. Conversely, the surgical modality (laparotomic vs laparoscopic and hysterectomy with bilateral salpingo-oophorectomy vs local excision) and pelvic lymphadenectomy were not. Even the different modalities of adjuvant therapy (hormonal therapy, radiotherapy, and chemotherapy) showed no prognostic significance. Tumor fragmentation/morcellation and higher mitotic count resulted independent prognostic variables at multivariate analysis. Conclusions: This data supports the avoidance of any type of morcellation if LG-ESS is suspected preoperatively. Higher mitotic count and, possibly, tumor size, advanced FIGO stage, necrosis, and LVSI could be exploited to tailor the adjuvant therapy, but these results need to be confirmed in larger prospective studies.