Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

BACKGROUND: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. METHODS: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). RESULTS: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. CONCLUSIONS: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Histopathological findings in hysterectomy for cervical stenosis in postmenopausal women: A retrospective case series.

OBJECTIVE: To analyze the histopathological findings in postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis, evaluating the incidental findings of preinvasive or invasive uterine and cervical disease. METHODS: Retrospective case series of postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis at Gynecological Oncology Unit of Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico Aviano-National Cancer Institute from January 2014 to January 2021. RESULTS: During the study period, 36 women underwent hysterectomy for postsurgical cervical stenosis at our institution. Cervical stenosis occurred 10.2 ± 5.6 years from the onset of menopause. In particular, 26 (72.2%) patients underwent a single loop electrosurgical excision procedure or carbon dioxide (CO2)-laser conization before the onset of stenosis. The remaining 10 (27.8%) women had multiple surgical excision before the onset of stenosis. At the final histopathological analysis, 17 (47.2%) patients had a preinvasive or invasive gynecological disease. In particular, 9 cases of cervical disease (including 1 case of endocervical squamous cell carcinoma pT1a) and 6 cases of endometrial hyperplasia emerged. Also, 2 cases of tubo-ovarian diseases were found. CONCLUSIONS: Postsurgical cervical stenosis is a challenging clinical condition, especially in women treated for cervical intraepithelial neoplasia or microinvasive cervical cancer. As shown, cervical stenosis can prevent an adequate gynecological follow-up and a prompt diagnosis of malignancies. Therefore, postmenopausal women with cervical stenosis should be carefully counseled, and hysterectomy could be a reasonable option, especially in those cases in which a conservative approach is not feasible, failed, or is not accepted by the patient.

Spontaneous angular dichorionic diamniotic twin pregnancy: a case report.

OBJECTIVE: To report a peculiar case of ultrasound diagnosis of spontaneous angular twin pregnancy. In literature, the terms "angular," "interstitial," and "cornual" pregnancies are often used inappropriately. Confusion in terminology may have contributed to difficulties in developing diagnostic ultrasound criteria to differentiate these ectopic pregnancies. DESIGN: Case report. SETTING: Obstetrics and Gynecology, Community Hospital "S. Maria delle Croci." PATIENT: A 28-year-old patient with a previous cesarean delivery was admitted to our hospital for management of a presumed angular ectopic pregnancy. Transvaginal ultrasound confirmed an ectopic dichorionic diamniotic twin pregnancy eccentrically located in the right superior angle of the uterine cavity: the first gestational sac appeared to have right angular implantation, whereas the second gestational sac seemed to deepen inside the myometrium, with a thin myometrial margin of only 3 mm. INTERVENTIONS: After discussing the risks, the patient requested to proceed with termination. A single intramuscular injection of 75 mg of methotrexate was administered, followed by ultrasound-guided hysterosuction after 19 days due to severe vaginal bleeding. MAIN OUTCOME MEASURES: An early and accurate ultrasound diagnosis of a high-risk condition allowed for conservative medical treatment. RESULTS: The serum beta-human chorionic gonadotropin levels progressively decreased. After 1 month, a clinical and ultrasound examination showed a regular endometrial line with a regular reappearance of menstrual bleeding. CONCLUSIONS: Although there are remarkable advances in ultrasound techniques, angular pregnancy remains a condition of difficult diagnosis and management; it is potentially dangerous and may lead to severe complications. An early and accurate diagnosis of this condition is necessary to avoid complications and individualize the subsequent management.

Atypical Endometrial Hyperplasia and Unexpected Cancers at Final Histology: A Study on Endometrial Sampling Methods and Risk Factors.

BACKGROUND: Up to 40% of women with atypical endometrial hyperplasia (AEH) can reveal endometrial cancer (EC) at hysterectomy. The pre-operative endometrial sampling method (ESM) and some independent cancer predictors may affect this outcome. The present study aimed to compare the rate of EC at hysterectomy in women with AEH undergoing dilation and curettage (D&C), hysteroscopically-guided biopsy (HSC-bio), or hysteroscopic endometrial resection (HSC-res). The secondary outcome was to compare the reliability of ESMs in women showing independent variables associated with EC. METHODS: Two-hundred-and-eight consecutive women with AEH and undergoing hysterectomy between January 2000 and December 2017 were analyzed retrospectively. Based on pre- and post-test probability analysis for EC, three ESMs were compared: D&C, HSC-bio, and HSC-res. Univariate and multivariate analyses were performed to assess risk factors predicting cancer on final histology. Finally, the patient's characteristics were compared between the three ESM groups. RESULTS: D&C and HSC-bio included 75 women in each group, while HSC-res included 58 women. Forty-nine women (23.6%) revealed cancer at hysterectomy (pre-test probability). Post-test probability analysis showed that HSC-res had the lowest percentage of EC underestimation: HSC-res = 11.6%; HSC-bio = 19.5%; D&C = 35.3%. Patient characteristics showed no significant differences between the three ESMs. Multivariate analysis showed that body mass index ≥40 (Odds Ratio (OR) = 19.75; Confidence Intervals (CI) 2.193-177.829), and age (criterion > 60 years) (OR = 1.055, CI 1.002-1.111) associated significantly with EC. In women with one or both risk factors, post-test probability analysis showed that HSC-res was the only method with a lower EC rate at hysterectomy compared to a pre-test probability of 44.2%: HSC-res = 19.96%; HSC-bio = 53.81%; D&C = 63.12%. CONCLUSIONS: HSC-res provided the lowest rate of EC underestimation in AEH, also in women showing EC predictors. These data may be considered for better diagnostic and therapeutic planning of AEH.

HPV Vaccination: The Position Paper of the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV).

Human papillomavirus (HPV) related cervical cancer represents an issue of public health priority. The World Health Organization recommended the introduction of HPV vaccination in all national public programs. In Europe, vaccines against HPV have been available since 2006. In Italy, vaccination is recommended and has been freely offered to all young girls aged 11 years since 2008. Three prophylactic HPV vaccines are available against high- and low-risk genotypes. The quadrivalent vaccine contains protein antigens for HPV 6, 11, 16, and 18. The bivalent vaccine includes antigens for HPV 16 and 18. The nonavalent vaccine was introduced in 2014, and it targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Clinical trials demonstrated the effectiveness of the three vaccines in healthy young women. Likewise, all vaccines showed an excellent safety profile. The bivalent vaccine provides two doses in subjects aged between 9 and 14 years and three doses in subjects over 14 years of age. The quadrivalent vaccine provides two doses in individuals from 9 to 13 years and three doses in individuals aged 14 years and over. The nonavalent vaccine schedule provides two doses in individuals from 9 to 14 years of age and three doses in individuals aged 15 years and over at the time of the first administration. Preliminary results suggest that the HPV vaccine is effective in the prevention of cervical squamous intraepithelial lesions even after local treatment. Given these outcomes, in general, it is imperative to expand the vaccinated target population. Some interventions to improve the HPV vaccine's uptake include patient reminders, physicians-focused interventions, school-based vaccinations programs, and social marketing strategies. The Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV) is committed to supporting vaccination programs for children and adolescents with a catch-up program for young adults. The SICPCV also helps clinical and information initiatives in developing countries to decrease the incidence of cervico-vaginal and vulvar pathology.

Comparison of uterine fibroids' growth pattern during pregnancy according to fetal sex: an observational study.

BACKGROUND: To investigate the effect of fetal sex on fibroids' growth during pregnancy according to the hCG serum levels METHODS: Observational study conducted from January 2007 to December 2016 on women with ultrasound identification of uterine fibroids who had a pregnancy within 1 year from diagnosis. The fibroids diameter was determined during the pre-pregnancy ultrasound, early first trimester (5-7 weeks), late first trimester (11-13 weeks), second trimester (19-21 weeks), and third trimester (31-33 weeks). The diameter growth was calculated in each interval between two ultrasounds. The hCG serum levels were determined both in early and late first trimester. The correlation between hCG levels and fibroid diameter was evaluated. Obstetric outcomes collected were gestational weeks at birth and the rate of cesarean section. Neonatal outcomes were birthweight and Apgar score at 1 min. RESULTS: Eighty-seven of the included women had a male fetus, and 70 had a female fetus. A progressive increase of fibroid diameter was observed from pre-pregnancy to second trimester for both fetal sexes. In third trimester, the mean ± SD fibroid diameter of female fetuses showed a slowdown, while the mean ± SD fibroid diameter of male fetuses continued to grow. Women carrying a female fetus presented a higher fibroid diameter in early first trimester (33.5 ± 13.3 mm vs 27.4 ± 11.0 mm, p < 0.01), late first trimester (40.2 ± 13.9 mm vs 34.6 ± 11.7 mm, p < 0.01), and second trimester (40.5 ± 14.9 mm vs 34.7 ± 10.3 mm, p < 0.01). The hCG serum levels resulted higher in women with a female fetus: 61406 (50554-71760) mU/ml vs 46016 (37160-56744) mU/ml (p < 0.01). A positive correlation between hCG levels and fibroid diameter was found both for male and female fetuses (male r = 0.77, 95% CI 0.71-0.82, p < 0.01 and female r = 0.82, 95% CI 0.76-0.86, p < 0.01). CONCLUSION: Women with female fetus seem to have a higher growth of fibroids up to second trimester of pregnancy. This process may be mediated by the higher serum hCG levels found in women expecting a female fetus.

The association between childbirth, breastfeeding, and uterine fibroids: an observational study.

The aim of this study was to investigate the effect of childbirth and breastfeeding on uterine fibroids and to identify the factors associated with size variations. This was a monocenter observational study carried on women with a sonographic diagnosis of uterine fibroids from January 2007 to December 2016, with no indication for immediate treatment, and who became pregnant within one year from diagnosis. All patients were re-evaluated six months after delivery. Fibroid diameters were compared between pre-pregnancy period, first, second, third trimester and post-delivery. The rate of "regressed" (growth of diameter <-40%), "unchanged" (growth of diameter between -40% and +40%) or "increased" (growth of diameter >+40%) fibroids at the post-delivery evaluation with respect to the pre-pregnancy state was calculated. One-hundred fifty-seven women were included in the final analysis. At the post-delivery ultrasound, a significant reduction of the fibroid diameter with respect to all previous examinations was observed, and there was no evidence of 67 (37.2%) fibroids. Ongoing breastfeeding was positively associated with an "unchanged" or "regressed" fibroid diameter (adOR 3.23, 95%CI: 1.35-7.70, p < 0.01). Smaller pre-gravidic fibroids were more likely to return to pre-pregnancy dimensions or to regress, with a cut-off of 32 mm for lactating women and of 26 mm for non-lactating women. In conclusion, fibroids seem to return to pre-pregnancy dimensions or to regress in the post-partum period. This process may be sustained by uterine involution and hormonal variations, with an additional role of breastfeeding.

Long-term observational approach in women with histological diagnosis of cervical low-grade squamous intraepithelial lesion: an Italian multicentric retrospective cohort study.

OBJECTIVE: To evaluate the risk of progression to high-grade squamous intraepithelial lesion (HSIL) (CIN2-3) or invasive cancer in women with histopathological diagnosis of low-grade squamous intraepithelial lesion (LSIL) (CIN1), managed in a long-term observational approach up to 5 years. DESIGN: Retrospective cohort study. SETTING: Four tertiary referral hospital. PARTICIPANTS: 434 women with adequate colposcopy and complete colposcopic charts were included in the present analysis. Women with glandular lesions on the referral cytology or previous diagnosis of cervical dysplasia or invasive cervical cancer or with synchronous vaginal, or with HIV infection or immunodepression were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The main study outcome was the rate of progression to histopathological HSIL (CIN2-3) or invasive cancer at any time during 5 years of follow-up. The possible risk factors were also evaluated. As secondary outcome, we analysed the possible risk factors at the 24-month evaluation for histopathological HSIL (CIN2-3) or invasive cancer progression between 2 and 5 years from initial diagnosis. RESULTS: A progression to histopathological HSIL (CIN2-3) was found in a total of 32 (7.4%) cases during 5 years of follow-up. A histopathological diagnosis of HSIL (CIN3) was found in four patients (0.9%) and no case of invasive cancer was detected. High-grade cytology at inclusion and the presence of a positive high-risk human papillomavirus (HR-HPV) DNA test at 2 years from inclusion maintained a significant correlation with the risk of histopathological progression to HSIL (CIN2-3). CONCLUSIONS: The results of our study showed a low rate (7.4%) of histopathological progression to HSIL (CIN2-3) in women with LSIL (CIN1) diagnosis during long-term follow-up up to 5 years. In case of positive HR-HPV DNA test at the 2 years evaluation an excisional treatment could be the preferred choice to prevent progression to HSIL (CIN2-3) in the following years, preferring a continuation of follow-up in case of HR-HPV DNA negative result.

Data on post-partum evaluation of women with abnormal cervical cytology in pregnancy.

During pregnancy, the only diagnosis that may alter management is invasive cancer. Thus, the primary aim of the cytological screening and subsequent colposcopy performed during pregnancy should be the exclusion of invasive cancer, "Practice Bulletin No. 140: management of abnormal cervical cancer screening test results and cervical cancer precursors," (American College of Obstetricians and Gynecologists, 2013) [1]. However, the impact of the delivery on the regression of the cervical lesions is still debated. This data article concerns the post-partum evaluation of colposcopic patterns, cytological and histopathology findings in women diagnosed with abnormal cervical cytology in pregnancy, included in the paper entitled "Reliability of colposcopy during pregnancy" (Ciavattini et al., 2018). Data about the rates of persistence, progression and regression of CIN after delivery are reported.

Reliability of colposcopy during pregnancy.

OBJECTIVE: To investigate the reliability of colposcopy during pregnancy and to evaluate the concordance between colposcopic patterns and histopathological findings in these women. STUDY DESIGN: Multicenter observational study of women diagnosed with an abnormal cervical cytology, who subsequently underwent a colposcopic evaluation with cervical biopsy during pregnancy. The "colpo-histopathological concordance‿ was evaluated. The "colposcopic overestimation and underestimation‿ were evaluated as well. RESULTS: 69 women, fulfilling the study inclusion/exclusion criteria, constituted the study cohort. Among them, on colposcopic examination, 14 women (20.3%) showed "grade I abnormal colposcopic findings‿, 52 (75.4%) showed "grade II abnormal colposcopic findings‿ and the remaining 3 women (4.3%) had a "suspicious for invasion‿ colposcopy. The histopathological diagnosis showed 2 negative biopsies, 12 (17.4%) cases of CIN1, 50 (72.5%) cases of CIN2 and 5 (7.2%) cases of invasive cervical cancer. We found a colposcopic overestimation in 10 cases (14.5%), underestimation in 12 cases (17.4%), and a concordance in 47 cases (68.1%). A better reliability of colposcopy in women in the firsts two trimesters and in particular in women ≤20 weeks pregnant was found (Cohen's weighted kappa: 0.65). CONCLUSIONS: When performed by gynecologists with expertise, colposcopy is a reliable diagnostic tool, even during pregnancy. Whenever possible, a colposcopic evaluation during the first half of pregnancy is preferable.

Follow up in women with biopsy diagnosis of cervical low-grade squamous intraepithelial lesion (LSIL): how long should it be?

AIM: To analyse the regression rate and the risk of persistence or progression of the lesions in women with a histopathological diagnosis of cervical low-grade squamous intraepithelial lesion (LSIL). MATERIALS AND METHODS: Retrospective cohort study of women with biopsy diagnosis of cervical LSIL, from January 2010 to December 2013. After the initial diagnosis of LSIL, all the women underwent scheduled follow-up examinations with cytology every 6 months for 2 years and an HPV test after 1 year. RESULTS: At the 24 -month follow-up, the regression of cervical LSIL was observed in 88.5% of the women. 10.8% of the women had a persistent lesion, while a progression towards cervical HSIL was reported in 0.7% of the women. The risk of persistence or progression of histological LSIL was higher in women with ASC-H or HSIL on the referral cytology and in tobacco users. CONCLUSION: In women with biopsy diagnosis of cervical LSIL, preceded by ASCUS or LSIL on cytology, a high rate of regression was observed and, in most of the cases, the regression occurred in the first year of follow-up. In women with cervical LSIL, preceded by ASC-H or HSIL on cytology, and in tobacco users, a higher risk of persistence and progression was observed. Thus, in these cases, repeated follow-up examinations, even with the HR-HPV test, are advisable.