Enhancing precision in hysteroscopic surgery: The role of intraoperative ultrasound.

Hysteroscopy stands as the gold-standard approach for managing intrauterine pathology. However, in complex clinical cases, hysteroscopic evaluation alone may prove insufficient for the safest and successful patient management. Intraoperative ultrasound (IOUS) has emerged as a valuable adjunct to hysteroscopic surgery, offering real-time visualization of endometrial cavity, uterine walls and instruments within the uterine cavity, enabling precise delineation of anatomical structures, and helping to assess the extent of pathology during intricate interventions. This review aims to comprehensively assess the applications, efficacy and utility of IOUS in hysteroscopic surgery. Available evidence indicates that in hysteroscopic myomectomy, IOUS significantly reduces the risk of uterine perforation, particularly in submucosal FIGO 2 myomas, and enhances the likelihood of a single-step procedure. During hysteroscopic metroplasty, ultrasound guidance decreases the chance of incomplete uterine septum resection. In the hysteroscopic management of severe Asherman syndrome, IOUS reduces the risk of uterine perforation or false passage. For cesarean scar pregnancy (CSP), ultrasound is crucial in defining the most appropriate surgical approach and is effective in guiding the hysteroscopic treatment of endogenic CSP. The use of IOUS in hysteroscopy proves valuable in complex cases where the risk of uterine perforation or incomplete procedure is increased.

Reproductive and oncologic outcomes in young women with uterine sarcoma undergoing fertility-sparing treatment: a systematic review.

Background: Uterine sarcomas (US) are rare cancer of possible occurrence even in women of childbearing age. To date, total hysterectomy is the standard treatment in the early stages. The possibilities of carrying out fertility-sparing treatments (FST) to save the fertility of women with unfulfilled reproductive desires are described in the literature, but to date, they can only be considered experimental. Objective: The aim of this systematic review was to evaluate the oncological and reproductive outcomes of women with different histological types of US undergoing FST. Design: Systematic review. Data sources and methods: Electronic databases were searched for English-language studies describing FST for US until January 31, 2024. Results: Forty-five papers which met the abovementioned inclusion criteria, were included in the qualitative analysis. Quantitative analysis was not possible because of the heterogeneity of the data. A descriptive summary of the results according to the histotype of US was provided. Six hundred forty-one patients of childbearing age with US and undergoing FST. After treatment with FST, 89 (13.9%) disease recurrences and 107 (16.7%) pregnancies were recorded. Conclusion: In selected cases of early-stage US, FST may be proposed. However, the patient must be informed of the real possibility of recurrence and potentially difficult achievement of pregnancy. Additional well-designed prospective studies and clinical trials are needed to address the knowledge gaps and enhance clinical decision-making in this population. Trial registration: PROSPERO ID: CRD42024509356.

Conservative treatment of cesarean scar pregnancy with the combination of methotrexate and mifepristone: A systematic review.

BACKGROUND: Cesarean scar pregnancy (CSP) has become more frequent as a direct consequence of the increased number of cesarean deliveries and the advances in imaging. Although some cases are characterized by spontaneous resolution, unrecognized or mishandled CSP has the potential to cause both fetal and maternal morbidity and mortality. However, due to its infrequency, there is no agreement on the best management. OBJECTIVE: The purpose of this study was to evaluate the safety, the risks and effectiveness of medical therapy with methotrexate and mifepristone to better understand its role in CSP therapy. DESIGN: This study is a systematic review. DATA SOURCES AND METHODS: The electronic databases PubMed, Medline, and Scopus were comprehensively searched until December 2023. Medical Subject Headings terms (Cesarean scar pregnancy) AND (Methotrexate) AND (Mifepristone) AND (Medical Therapy) were used to identify the relevant records. Due to the rarity of this pathology, the studies included are all case reports or case series. The methodological quality of the included studies was assessed using the JBI Critical Appraisal Checklist for case reports. RESULTS: We included in our review a total of seven cases reported in five manuscripts at the end of the screening process. Our review suggests that this type of combination treatment can be considered. The success rate is 71.4%. Treatment seems to be most effective when beta human chorionic gonadotropin (B-hCG) is below 5,000 mUi/ml and when the gestational sac is less than 20 mm. The absence of fetal heartbeat seems to be a positive prognostic factor for a positive outcome. CONCLUSION: Methotrexate and mifepristone administration can be considered as an alternative first-line effective treatment, especially in case of pregnancy with B-hCG <5,000 mUi/ml and when the gestational sac is less than 20 mm. It is important to individualize the management and treatment according to the clinical condition, the patient's age, number of previous cesarean deliveries, willingness to have other children, and the physicians' experience.

Unrecognized Cesarean Scar Pregnancy has the potential to cause both fetal and maternal morbidity and mortality. Methotrexate (MTX) and Mifepristone administration can be considered as an alternative first-line effective treatment especially in case of pregnancy with a low BHCG and when the gestational sac is less than 20 mmCesarean scar pregnancy (CSP) has become more frequent as a direct consequence of the increased number of Cesarean deliveries and the advances in imaging. Unrecognized CSP has the potential to cause both fetal and maternal morbidity and mortality. However, there is no agreement on the best management. The purpose of this study was to evaluate the safety, the risks, and effectiveness of medical therapy with methotrexate and mifepristone. The electronic databases PubMed, Web of Science, and Scopus were comprehensively searched until December 2023. We included in our review a total of seven cases reported in five5 manuscripts at the end of the screening process. Our review suggests that this type of combination treatment can be considered. The success rate is 71.4%. Treatment seems to be most effective when B-hCG is below 5000 mUi/ml and when the gestational sac is less than 20 mm. methotrexate (MTX) and mifepristone administration can be considered as an alternative first-line effective treatment.

Rapid and random-start endometrial preparation before outpatient hysteroscopic polypectomy in patients of perimenopausal age.

OBJECTIVE: This study aimed to assess the efficacy of randomly started oral dienogest/ethinylestradiol (DNG/EE) for swift endometrial preparation prior to outpatient hysteroscopic polypectomy in perimenopausal women. METHOD: A multicenter, prospective, randomized controlled trial was conducted in university hospitals. Eighty perimenopausal women scheduled for outpatient hysteroscopic polypectomy between January 2023 and March 2024 were randomly assigned to either intervention (n = 40) or control (n = 40) groups. Exclusion criteria included concomitant endometrial pathologies, recent therapy and adnexal diseases. The intervention group received oral DNG/EE 2 mg/0.03 mg/day started on any day of the menstrual cycle for 14 days. The control group underwent polypectomy between menstrual cycle days 8 and 11 without pharmacological treatment. RESULTS: Pre-procedure (p < 0.001) and post-procedure (p < 0.001) endometrial thickness were significantly reduced in the intervention group, along with a higher incidence of hypotrophic/atrophic endometrial patterns (p < 0.001). Surgical parameters also differed significantly between groups. CONCLUSION: DNG/EE treatment offers rapid, cost-effective endometrial preparation, enhancing surgical outcomes and patient satisfaction during outpatient polypectomy. TRIAL REGISTRATION: ClinicalTrials.gov NCT06316206.

Susceptibility to Infection and Impact of COVID-19 Vaccines on Symptoms of Women with Endometriosis: A Systematic Review and Meta-Analysis of Available Evidence.

Women with endometriosis were deemed more prone to COVID-19 infection in some reports. Considering that endometriosis-related aberrant immune response, understanding how COVID-19 vaccination influences its clinical status is crucial. The aim of this meta-analysis was the evaluate the susceptibility to COVID-19 infection and modifications of symptoms following COVID-19 vaccination in women with endometriosis. Electronic searches on EMBASE, MEDLINE, Scopus, Cochrane at CENTRAL, Scielo.br, LILACS and other databases were searched from inception to March 2024. Studies were eligible if they analyzed the incidence of infection in endometriosis women or the changes in symptoms after two doses of COVID-19 vaccine and had a control group. Four studies (2249 women) were included. No increased susceptibility to COVID-19 infection due to presence or absence of endometriosis was retrievable (risk ratio (RR) 1.42 [95% CI 0.88 to 2.27]; I2 = 33%). Patients with endometriosis did not experience an overall worsening of symptomatology relative to controls (RR 1.58 [95% CI 0.67 to 3.75]; I2 = 94%). An increase in the risk of dysmenorrhea worsening was noted (RR 1.88 [95% CI 1.11 to 3.17]; I2 = 63%). No other differences regarding menstrual flow (RR 1.25 [95% CI 0.70 to 2.23]; I2 = 78%), intermenstrual bleeding (RR 1.14 [95% CI 0.83 to 1.56]; I2 = 39%) and pelvic pain (RR 2.55 [95% CI 0.65 to 10.05]; I2 = 80%) compared to controls was retrievable. Therefore, mRNA vaccines do not seem to lead to worsening of symptomatology in endometriotic women. However, a slight temporary increase in dysmenorrhea may be present. Moreover, endometriosis does not seem to increase the risk of contracting COVID-19.

Efficacy and Diagnostic Reliability of Intraoperative Frozen Section in the Surgical Management of Early-Stage Cervical Cancer.

OBJECTIVES: The aim of this study of this study was to evaluate preoperative radiology and histopathology findings in cervical cancer lymphadenopathy detection, allowing targeted frozen section examination (FSE). DESIGN: A retrospective analysis was conducted of 203 early-stage cervical cancer patients between 2010 and 2019 in a tertiary centre. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: All patients had histologically confirmed cervical cancer and underwent magnetic resonance imaging (MRI) prior to intraoperative FSE. The primary objectives of the study were to determine the diagnostic accuracy of intraoperative FSE in the identification of lymph node metastases (LNM) in early-stage cervical cancer by correlation with final results obtained using standard histopathology techniques and to examine different preoperative, intraoperative, demographic, radiological, and histopathological factors that could identify those at greatest risk of nodal disease and hence predict those most likely to benefit from FSE, enabling more selective and targeted use. RESULTS: Nineteen patients were found to have LNM (9.36%) at FSE. Patients were at increased risk of LNM by 6-fold with positive LVSI, 3-fold with MRI lymphadenopathy, and 3.5-fold with MRI-visible disease. The presence of lymphadenopathy on MRI and positive LVSI in combination increased the risk of LNM by 19-fold. LIMITATIONS: We acknowledge that FSE is expensive and time intensive, exposing patients to increased surgery duration and associated risk. We also recognize that it may not be feasible for all patients. Finally, the analysis is limited by retrospective nature of the study. CONCLUSIONS: By application of the preoperative risk stratification algorithm, we may suggest that FSE can be a useful tool in high-risk patients.

Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review.

Objective: To evaluate the reproductive outcomes of patients bearing BRCA-1 and BRCA-2 mutations. Methods: In this retrospective observational cohort study, we assessed data from BRCA-1 and BRCA-2 carriers, analyzing demographics, oncological history, and reproductive outcomes. Statistical analysis compared BRCA-1 and BRCA-2 carriers. A thorough review of the literature was carried out. Results: Fifty-eight patients were included. BRCA-1 and BRCA-2 mutations were equally distributed. Eighty-nine pregnancies occurred in our series, hesitated in 73 live births and 19 miscarriages. Mean age at first and last pregnancy was 27.8 ± 4.8 and 31.6 ± 4.8 years old. Thirty-nine patients have had at least one live birth (67.2%). Mean number of live births was 1.9 ± 0.6. Live birth rate (LBR) was 81.1% and miscarriage rate was 32.8%. Spontaneous fertility was unaltered, as evidenced by high LBR. Subgroup analysis revealed no significant differences between BRCA-1 and BRCA-2 carriers. Conclusions: Our results shows that spontaneous reproductive outcomes in BRCA-mutated patients are reassuring. Despite evidence indicating a decrease in ovarian reserve among BRCA patients, this factor seems to not impact spontaneous fertility negatively. Further research is needed, and individuals with BRCA mutations should consider early family planning and fertility preservation in case of partner absence.

Evaluation of the benefit of indocyanine green as an educational and practical tool for ureteral identification in laparoscopic pelvic surgery: a cross-sectional study.

BACKGROUND: Indocyanine green (ICG) is a visible near-infrared fluorescent dye. Several studies have reported its benefit in identifying important anatomical structures, tissue vascularization, and sentinel lymph nodes in the case of tumors. Studies have shown that ICG is critical and safe in gynecologic surgeries. However, research on how ICG dye can help surgeons in laparoscopic surgeries correctly identify the course of the ureter has yet to be further investigated. METHOD: This cross-sectional study enrolled 62 gynecology attending and resident surgeons who were asked to identify the course of the ureter on images of laparoscopic surgeries. The results were then compared with images in which ICG dye highlighted the course of the ureter. The purpose of this study was to detect the ability of surgical assistants and residents to adequately identify the course of the ureter in laparoscopic pelvic surgeries. RESULTS: No statistically significant differences were found in terms of year of residency, years of experience, number of laparoscopic procedures attended, and correct identification of ureter course. ICG proved useful in identifying the correct ureteral trajectory. CONCLUSIONS: ICG can be a valuable tool to improve the correct identification of ureters and improve surgical outcomes.

Sleep disorders and hyperarousal among patients with endometriosis: A case-control survey study.

BACKGROUND: Endometriosis has been associated with sleep disorders, and hyperarousal appears to be involved in their pathogenesis; however, the presence of hyperarousal in the endometriosis population was never investigated. METHODS: We conducted a case-control survey study by sending a questionnaire to all endometriosis patients followed up at our Centers. Controls were recruited among the general population. The questionnaire included demographic information, symptoms and history of endometriosis, the Hyperarousal Scale (H-Scale), the Pittsburgh Sleep Quality Index (PSQI), and the Insomnia Severity Index (ISI). RESULTS: A total of 847 women completed the questionnaires: 430 (50.8 %) had endometriosis, and 417 (49.2 %) were controls. Endometriosis was associated with higher H-scale score (OR 2.9, 95 % CI 2.4-3.8, p = 0.000), higher PSQI score (OR 4.3, 95 % CI 3.2-5.7, p = 0.000), and higher ISI score (OR 4.6, 95 % CI 3.5-6.1, p = 0.000) in multivariable ordinal logistic regressions analysis. With path analysis, hyperarousal (H-Scale) reported a partial mediating role in the association between endometriosis and sleep disorders. The mediation effect represented 22.3-27.8 % of the entire association between endometriosis and sleep disturbances. CONCLUSION: Endometriosis patients complaining sleep disorders may benefit by investigating the presence of hyperarousal given cognitive behavioral therapy was reported effective in improving hyperarousal and associated sleep disorders.

Efficacy of letrozole for the treatment of tubal ectopic pregnancy: A meta-analysis.

BACKGROUND: Tubal ectopic pregnancy (EP) is a life-threatening condition, especially if undiagnosed or misdiagnosed, tipically in low income countries and/or where women have limited access to health care. The current management protocol of tubal EP consists of either surgical management, or medical management with methotrexate. Recent studies, while few, have suggested that letrozole, an aromatase inhibitor, may play a role in the medical treatment of tubal EP. OBJECTIVES: To evaluate the effectiveness of letrozole alone in the medical treatment of tubal EP. SEARCH STRATEGY: Electronic databases were searched until 31 December 2023. SELECTION CRITERIA: Retrospective or prospective studies reporting the treatment of tubal EP with letrozole alone were considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: Pooled results were expressed as OR with 95 %CI. Heterogeneity was assessed using Higgins I2. Subgroup analysis was performed to compare outcomes according to time after intervention. Subgroup differences were checked through χ2 test. RESULTS: A total of 152 patients were included. Seventy-nine patients (51.97 %) were treated with letrozole, 39 patients (16.54 %) with methotrexate, and 34 patients (31.49 %) underwent surgical treatment. Pooled data analysis supports the consistency of the effect of letrozole in reducing ß-hCG over time at a comparable rate among studies, and that treatment with letrozole is superior to surgery and has the same efficacy as methotrexate. However, all the included studies were judged at high risk of bias in terms of study design, sample representativeness, and sampling technique. Furthermore, short and long term side effects were not reported in any of the included studies. CONCLUSIONS: Letrozole is a promising alternative to methotrexate and surgical therapy in the treatment of tubal EP. Although this meta-analysis suggests efficacy and low hazard of the drug and encourages its application, the data available today remain extremely sparse, which weakens any claims that can be made, and is not sufficient to assert that letrozole is safe and effective in the treatment of EPs. There is an absolute need for randomized studies with accurate patient selection, fixed doses, large sample sizes, and reporting of short- and long-term side effects to refute or confirm this assumption.

Inositol Restores Appropriate Steroidogenesis in PCOS Ovaries Both In Vitro and In Vivo Experimental Mouse Models.

Androgen excess is a key feature of several clinical phenotypes of polycystic ovary syndrome (PCOS). However, the presence of FSH receptor (FSHR) and aromatase (CYP19A1) activity responses to physiological endocrine stimuli play a critical role in the pathogenesis of PCOS. Preliminary data suggest that myo-Inositol (myo-Ins) and D-Chiro-Inositol (D-Chiro-Ins) may reactivate CYP19A1 activity. We investigated the steroidogenic pathway of Theca (TCs) and Granulosa cells (GCs) in an experimental model of murine PCOS induced in CD1 mice exposed for 10 weeks to a continuous light regimen. The effect of treatment with different combinations of myo-Ins and D-Chiro-Ins on the expression of Fshr, androgenic, and estrogenic enzymes was analyzed by real-time PCR in isolated TCs and GCs and in ovaries isolated from healthy and PCOS mice. Myo-Ins and D-Chiro-Ins, at a ratio of 40:1 at pharmacological and physiological concentrations, positively modulate the steroidogenic activity of TCs and the expression of Cyp19a1 and Fshr in GCs. Moreover, in vivo, inositols (40:1 ratio) significantly increase Cyp19a1 and Fshr. These changes in gene expression are mirrored by modifications in hormone levels in the serum of treated animals. Myo-Ins and D-Chiro-Ins in the 40:1 formula efficiently rescued PCOS features by up-regulating aromatase and FSHR levels while down-regulating androgen excesses produced by TCs.

Role of V-Y flap reconstruction in vulvar cancer patients: multicenter retrospective study.

OBJECTIVE: To assess if the use of a V-Y reconstructive flap after excisional radical surgery positively influences the surgical outcomes in patients with vulvar cancer. METHODS: This was a multicenter, retrospective, controlled study. Surgical outcomes and complication rates of women with invasive vulvar cancer who underwent radical surgery and vulvar reconstruction and those who underwent radical surgery without the reconstruction step were compared. Only patients who underwent bilateral or unilateral V-Y advancement fascio-cutaneous flaps were included in the reconstruction group. Univariate and multivariate logistic regression models were used to analyze predicting variables for their association with complication rates. RESULTS: Overall, 361 patients were included: 190 (52%) underwent the reconstructive step after the excisional radical procedure and were compared with 171 (47.4%) who did not undergo the reconstructive step. At multivariate analysis, body mass index >30 kg/m2 (odds ratio (OR) 3.36, p=0.007) and diabetes (OR 2.62, p<0.022) were independently correlated with wound infection. Moreover, increasing age (OR 1.52, p=0.009), body mass index >30 kg/m2 (OR 3.21, p=0.002,) and International Federation of Gynecology and Obstetrics (FIGO) stages III-IV (OR 2.25, p=0.017) were independent predictors of wound dehiscence. A significant reduction in the incidence of postoperative wound complications among patients who underwent V-Y reconstructive flaps was demonstrated. This was correlated more significantly in women with lesions >4 cm. CONCLUSIONS: The adoption of V-Y flaps in vulvar surgery was correlated with reduced surgical related complications, particularly in vulnerable patients involving large surgical defects following excisional radical procedures.

Diagnosis and Management of Pelvic Congestion Syndrome: Comprehensive Review.

BACKGROUND: Pelvic congestion syndrome (PCS) is a poorly understood condition that can be associated with chronic pelvic pain and could impact quality of life. The diagnosis is often made by exclusion of other causes of pelvic pain. OBJECTIVE: The purpose of our review was to provide an update on the etiology, anatomy, physiology, identification, and the therapeutic management of PCS. METHOD: We conducted a literature review involving publications from 2003 to 2024 in PubMed, Elsevier, MEDLINE, as well as manual searches of primary and review articles using keywords such as "pelvic veins", "embolization", "venography", "pelvic congestion syndrome", and "chronic pelvic pain". CONCLUSION: PCS remains poorly understood. Symptoms can be non-specific and difficult to distinguish from other diseases; yet it is an important cause of chronic pelvic pain in women. To date, there have been only a small number of randomized trials and high-level evidence is still lacking. OUTLOOK: We call for an increased awareness of PCS and additional clinical studies in a large number of patients.

Lower limb lymphedema after surgical staging for endometrial cancer: Current insights and future directions.

Lower extremity lymphedema (LEL) is a common complication following surgical staging of endometrial cancer. LEL is a chronic condition associated with significant impact on patient morbidity and quality of life (QoL). This review aimed to report the current evidence in the literature on secondary LEL after surgical staging for endometrial cancer, focusing on the incidence based on different approaches to lymph node staging, diagnosis, risk factors, and the impact on QoL. Due to the absence of a standardized agreement regarding the methodology for evaluating LEL, the documented frequency of occurrence fluctuates across different studies, ranging from 0% to 50%. Systematic pelvic lymphadenectomy appears to be the primary determinant associated with the emergence of LEL, whereas the implementation of sentinel lymph node biopsy has notably diminished the occurrence of this lymphatic complication after endometrial cancer staging. LEL is strongly associated with decreased QoL, lower limb function, and negative body image, and has a detrimental impact on cancer-related distress reported by survivors. Standardization of lymphedema assessment is needed, along with cross-cultural adaptation of subjective outcome measures for self-reported LEL. The advent of sentinel lymph node mapping represents the ideal approach for accurate nodal assessment with less short- and long-term morbidity. Further research is needed to definitively assess the prevalence and risk factors of LEL and to identify strategies to improve limb function and QoL in cancer survivors with this chronic condition.

The effect of ulipristal acetate on tumor necrosis factor α, insulin-like growth factor 1, and plasminogen activator inhibitor-1 serum levels in patients with symptomatic uterine fibroids.

Introduction: Uterine fibroids (UFs) are benign tumors of the female reproductive system originating from the smooth muscle of the uterus. Currently, progesterone is known to play a key role in the differentiation of the myometrial tissue to form UFs and their abnormal growth. The mechanism of action of progesterone in UF tumorigenesis involves its effect on increasing the concentrations and dysregulation of selected growth factors. Material and methods: A retrospective cohort study was performed to evaluate and compare tumor necrosis factor α (TNF-α), insulin-like growth factor 1 (IGF-1), plasminogen activator inhibitor-1 (PAI-1) serum concentrations in patients with UFs without prior hormonal treatment, patients with UFs treated with a 3-month standard ulipristal acetate (UPA - a type of selective progesterone receptor modulator) scheme (5 mg/day) and in control patients without UFs. A total of 120 patients were divided into 3 groups (controls, UFs with UPA treatment, UFs without UPA treatment). Results: There were no significant differences in TNF-α serum concentrations between patients with UFs who underwent UPA treatment and patients who did not. Serum concentrations of IGF-1 and PAI-1 did not show significant intergroup differences. Conclusions: No significant differences were found between TNF-α concentrations in the serum of patients with UFs treated with UPA, and patients without UPA treatment. In addition, our data analysis did not show significant differences in the concentrations of IGF-1 and PAI-1 between patients with UFs and the control group. Further studies on the dependence of specific symptoms on selected growth factors are mandatory.

Impact of surgery on reproductive outcomes in women with deep endometriosis and proven presurgical infertility: Facts and controversies.

In women with proven infertility and deep endometriosis (DE), optimal management is controversial. To date, there is no clear evidence on the association between infertility and different stages of rASRM, nor is there clear guidance from leading scientific societies for surgical treatment of DE patients. A comprehensive literature search was conducted on the main databases for English-language trials describing the effectiveness of surgery for DE in patients with proven infertility; 16 studies were deemed eligible for inclusion in this systematic review (CRD42024498888). Quantitative analysis was not possible because of the heterogeneity of the data. A descriptive summary of the results according to location of pathology, surgical technique used, and whether assisted reproductive technology (ART) was needed or not was provided. A total of 947 infertile women were identified, 486 of whom became pregnant, with an average pregnancy rate of 51.3%. Our review suggests that surgery can be of valuable help in improving reproductive outcomes by improving the results of ART. It has not been possible to reach robust conclusions on the outcomes of surgery based on the location of DE because of the heterogeneity of evidence available to date. Overall, although some data encourage first-line surgical management, further investigation is needed to determine its effective application before or after ART failure.

Uterine perivascular epithelioid cell tumors (PEComa) and the accuracy of proposed classification systems in predicting the malignant versus non-malignant behavior.

OBJECTIVE: To compare the accuracy of available classification systems (Folpe, modified Folpe, Bennet, and Schoolmester) in predicting the behavior of uterine Perivascular Epithelioid Cell tumors (PEComas). METHODS: We reviewed the pathology registry to identify all uterine PEComas treated at our center. We conducted a systematic literature review searching electronic databases from inception to November 2023. We included all references reporting at least one case of uterine PEComa; cases associated with tuberous sclerosis complex were excluded. Patient-level data were extracted by identified records. Survival analysis was used to assess the accuracy of all proposed classification systems to classify uterine PEComas as malignant versus non-malignant. RESULTS: Six uterine PEComas were treated at our center. The literature search identified 101 uterine PEComas from 32 studies. Eighty-five out of 107 PEComas (28 studies and our series) reported enough follow-up data and details to apply all four classifications. The modified Folpe classification demonstrated the highest hazard ratio (HR) for relapse (HR:8.63; 95% confidence interval [CI] 2.06-36.1) and death due to PEComa (HR:6.8, 95%CI:0.89-51.6) for malignant versus non-malignant PEComas. Changing the cut-off of PEComa size to ≥8 cm and mitotic figures per 50 high power fields to ≥5, the HR for recurrence lowered (HR:6.26; 95% CI 2.20-17.80), but HR for death increased (HR:10.3; 95% CI 1.35-77.80). CONCLUSIONS: The modified Folpe classification was the most accurate in predicting the PEComa behavior. Changing the cut-off of PEComa size and number of mitotic figures may improve the accuracy in predicting death due to disease.