A. C. Testa

Ultrasound‐based risk model for preoperative prediction of lymph‐node metastases in women with endometrial cancer: model‐development study

ABSTRACTObjectiveTo develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph‐node metastases in women with endometrial cancer.MethodsA mixed‐effects logistic regression model for prediction of lymph‐node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph‐node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave‐center‐out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high‐risk defined as endometrioid cancer Grade 3/non‐endometrioid cancer) or combined endometrial biopsy and ultrasound (high‐risk defined as endometrioid cancer Grade 3/non‐endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread).ResultsLymphadenectomy was performed in 691 women, of whom 127 had lymph‐node metastases. The model for prediction of lymph‐node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68–0.78), the calibration slope was 1.06 (95% CI, 0.79–1.34) and the calibration intercept was 0.06 (95% CI, –0.15 to 0.27). Using a risk threshold for lymph‐node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high‐risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold.ConclusionsBased on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph‐node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (30): clinical and ultrasound characteristics of usual‐type and variants of leiomyoma

ABSTRACT Objective To characterize the clinical and ultrasound features of usual‐type leiomyoma and variants of leiomyoma. Methods This retrospective, single‐center study included patients with a histologically confirmed diagnosis of benign mesenchymal uterine tumor, prospectively collected between January 2019 and December 2021 in the MYometrial Lesion UltrasouNd And mRi (MYLUNAR) study. Tumors were classified according to the Morphological Uterus Sonographic Assessment criteria and grouped according to the 2020 World Health Organization (WHO) classification of female genital tumors into usual‐type and variant leiomyomas. The variants of leiomyoma were further classified into specific histological subtypes as defined in the WHO classification. Two ultrasound examiners independently reviewed all available ultrasound images to identify patterns associated with usual‐type leiomyoma and variants of leiomyoma. Results A total of 1766 patients were included, of whom 1383 (78.3%) had usual‐type leiomyoma and 383 (21.7%) had a variant of leiomyoma. The median age at diagnosis was 45 (range, 15–88) years, with no statistically significant difference between the two groups. Most patients were premenopausal, although the variant group had a higher proportion of postmenopausal patients compared with the usual‐type group (21.5% vs 12.6%; P  < 0.001). On ultrasound examination, leiomyoma variants were larger than usual‐type leiomyomas (median maximum diameter, 82.5 mm vs 70.0 mm; P  < 0.001) and more frequently exhibited cystic areas (33.2% vs 12.8%; P  < 0.001). Acoustic shadows were present in 79.1% of variants, compared with 90.4% in usual‐type leiomyomas (P  < 0.001). Some variant subtypes appeared only in premenopausal women and had distinct morphological characteristics. Epithelioid leiomyomas were the largest variant, with a median diameter of 139.5 mm. Mitotically active leiomyomas showed regular margins and uniform echostructure, and lacked cystic areas in almost all cases. Lipoleiomyomas contained calcifications in some cases. After reviewing the ultrasound images, 13 patterns were identified, some of which were distinctive of specific variant subtypes. Conclusion Patients with usual‐type vs variant leiomyomas presented with some distinct clinical and ultrasound characteristics. Among variants of leiomyomas, some histotypes exhibited distinctive clinical and ultrasound features. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound examiners' ability to describe ovarian cancer spread using preacquired ultrasound videoclips from a selected patient sample with high prevalence of cancer spread

ABSTRACTObjectivesTo assess the ability, as well as factors affecting the ability, of ultrasound examiners with different levels of ultrasound experience to detect correctly infiltration of ovarian cancer in predefined anatomical locations, and to evaluate the inter‐rater agreement regarding the presence or absence of cancer infiltration, using preacquired ultrasound videoclips obtained in a selected patient sample with a high prevalence of cancer spread.MethodsThis study forms part of the Imaging Study in Advanced ovArian Cancer multicenter observational study (NCT03808792). Ultrasound videoclips showing assessment of infiltration of ovarian cancer were obtained by the principal investigator (an ultrasound expert, who did not participate in rating) at 19 predefined anatomical sites in the abdomen and pelvis, including five sites that, if infiltrated, would indicate tumor non‐resectability. For each site, there were 10 videoclips showing cancer infiltration and 10 showing no cancer infiltration. The reference standard was either findings at surgery with histological confirmation or response to chemotherapy. For statistical analysis, the 19 sites were grouped into four anatomical regions: pelvis, middle abdomen, upper abdomen and lymph nodes. The videoclips were assessed by raters comprising both senior gynecologists (mainly self‐trained expert ultrasound examiners who perform preoperative ultrasound assessment of ovarian cancer spread almost daily) and gynecologists who had undergone a minimum of 6 months' supervised training in the preoperative ultrasound assessment of ovarian cancer spread in a gynecological oncology center. The raters were classified as highly experienced or less experienced based on annual individual caseload and the number of years that they had been performing ultrasound evaluation of ovarian cancer spread. Raters were aware that for each site there would be 10 videoclips with and 10 without cancer infiltration. Each rater independently classified every videoclip as showing or not showing cancer infiltration and rated the image quality (on a scale from 0 to 10) and their diagnostic confidence (on a scale from 0 to 10). A generalized linear mixed model with random effects was used to estimate which factors (including level of experience, image quality, diagnostic confidence and anatomical region) affected the likelihood of a correct classification of cancer infiltration. We assessed the observed percentage of videoclips classified correctly, the expected percentage of videoclips classified correctly based on the generalized linear mixed model and inter‐rater agreement (reliability) in classifying anatomical sites as being infiltrated by cancer.ResultsTwenty‐five raters participated in the study, of whom 13 were highly experienced and 12 were less experienced. The observed percentage of correct classification of cancer infiltration ranged from 70% to 100% depending on rater and anatomical site, and the median percentage of correct classification for the 25 raters ranged from 90% to 100%. The probability of correct classification of all 380 videoclips ranged from 0.956 to 0.975 and was not affected by the rater's level of ultrasound experience. The likelihood of correct classification increased with increased image quality and diagnostic confidence and was affected by anatomical region. It was highest for sites in the pelvis, second highest for those in the middle abdomen, third highest for lymph nodes and lowest for sites in the upper abdomen. The inter‐rater agreement of all 25 raters regarding the presence of cancer infiltration ranged from substantial (Fleiss kappa, 0.68 (95% CI, 0.66–0.71)) to very good (Fleiss kappa, 0.99 (95% CI, 0.97–1.00)) depending on the anatomical site. It was lowest for sites in the upper abdomen (Fleiss kappa, 0.68 (95% CI, 0.66–0.71) to 0.97 (95% CI, 0.94–0.99)) and highest for sites in the pelvis (Fleiss kappa, 0.94 (95% CI, 0.92–0.97) to 0.99 (95% CI, 0.97–1.00)).ConclusionsUltrasound examiners with different levels of ultrasound experience can classify correctly predefined anatomical sites as being infiltrated or not infiltrated by ovarian cancer based on video recordings obtained by an experienced ultrasound examiner, and the inter‐rater agreement is substantial. The likelihood of correct classification as well as the inter‐rater agreement is highest for sites in the pelvis and lowest for sites in the upper abdomen. However, owing to the study design, our results regarding diagnostic accuracy and inter‐rater agreement are likely to be overoptimistic. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pearls and Potential Pitfalls for Correct Diagnosis of Ovarian Cystadenofibroma in MRI: A Pictorial Essay

Ovarian cystadenofibroma is a benign ovarian tumor that is characterized by a consistent percentage of masses, which remain indeterminate in ultrasonography and require magnetic resonance (MR) investigation; they may mimic borderline or malignant lesions. Three main morphologic patterns, resembling different ovarian neoplasms, can be identified in cystadenofibromas: multilocular solid lesions, unilocular cystic lesions with parietal thickening, and purely cystic masses. However, a cystoadenofibroma has typical features, such as T2-weighted hypointensity associated with no restrictions in diffusion-weighted imaging (the so-called "dark-dark appearance") and progressive post-contrast enhancement (type I perfusion curve). The purpose of this study was to review the features of ovarian cystadenofibromas in MR imaging and to suggest pearls and pitfalls regarding their correct diagnosis.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on pre-operative diagnosis of ovarian tumors

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumors

ABSTRACTThe European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence‐based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models.ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence‐based, the current literature was reviewed and critically appraised.Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements.This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

Imaging in gynecological disease (29): clinical and ultrasound features of primary ovarian immature teratoma

ABSTRACT Objective To describe the clinical and ultrasound characteristics at the time of diagnosis of primary ovarian immature teratoma with no other germ cell tumor components described on histopathology. Methods This was a retrospective study of women with a histological diagnosis of primary ovarian immature teratoma who had undergone a preoperative ultrasound examination between 1998 and 2024. Cases were identified from the databases of 17 contributing ultrasound centers and the International Ovarian Tumor Analysis (IOTA) database. The descriptions of the ultrasound images of the tumors made by the original ultrasound examiners using IOTA terminology were reported. In addition, grayscale and color or power Doppler ultrasound images or videoclips were retrieved for all tumors. Two independent ultrasound examiners reviewed the retrieved material and searched for specific ultrasound characteristics of immature teratomas using pattern recognition. We present their agreed description of the tumors. Results In total, 64 patients with ovarian immature teratoma were included, of which 38 (59.4%) were obtained from the IOTA database (IOTA studies phase 1, 1b, 2, 3, 5 and 7). The median age of the patients at diagnosis was 24.5 (interquartile range (IQR), 18.8–31.0; range, 12–50) years. The most common presenting symptoms were abdominal or pelvic pain (38/60, 63.3%) and abdominal swelling (30/60, 50.0%). All immature teratomas were unilateral. The median largest diameter of the tumor was 149.5 (IQR, 125.0–183.8; range, 27–400) mm. Using IOTA terminology, most tumors were described as multilocular‐solid (32/64, 50.0%) or solid lesions (22/64, 34.4%). When present, the solid component had a median largest diameter of 98.5 (IQR, 59.8–146.8; range 6–400) mm. Most masses showed minimal (19/63, 30.2%) or moderate (35/63, 55.6%) vascularization on color or power Doppler ultrasound examination. Using pattern recognition, the most typical ultrasound feature was heterogeneous, bizarre echogenicity of the solid components, with hyperechogenic areas, cystic spaces and acoustic shadows. This feature, which we consider pathognomonic, was present in 48/57 (84.2%) immature teratomas in which the solid components were adequately assessable. Conclusions The typical ultrasound appearance of an ovarian immature teratoma is a large unilateral adnexal mass with large solid components that is poorly or moderately vascularized. The pathognomonic feature is heterogeneous echogenicity of the solid components with hyperechogenic areas, cystic spaces and acoustic shadows. Preoperative suspicion of immature teratoma can guide treatment, such as offering fertility‐sparing surgery. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of ultrasound with computed tomography and whole‐body diffusion‐weighted MRI in prediction of surgical outcome using ESMO ‐ ESGO criteria in patients with tubo‐ovarian carcinoma: prospective ISAAC study

ABSTRACT Objective To test the non‐inferiority of extended abdominopelvic ultrasound examination compared with contrast‐enhanced computed tomography (CT) and whole‐body diffusion‐weighted magnetic resonance imaging (WB‐DWI/MRI) in discriminating preoperatively between resectable and non‐resectable disease based on the European Society for Medical Oncology (ESMO) and European Society of Gynecological Oncology (ESGO)‐defined criteria in patients with tubo‐ovarian carcinoma. Methods The Imaging Study on Advanced ovArian Cancer was a prospective multicenter observational study conducted in five European gynecological oncology centers. All centers had ESGO accreditation to perform advanced ovarian cancer surgery, and ultrasound examinations were performed by a European Federation of Societies for Ultrasound in Medicine and Biology level‐III examiner in a standardized manner. Included in the analysis were patients enrolled between 2020 and 2022 with suspected or histologically proven primary tubo‐ovarian (including peritoneal) carcinoma who, for the purposes of the study, underwent ultrasound and CT imaging, as well as WB‐DWI/MRI if available, prior to surgery. The index tests, which included the preoperative imaging modalities as well as intraoperative exploration at the start of surgery, supplemented by biopsy or follow‐up imaging for extra‐abdominal locations, evaluated the presence of disease at eight anatomical sites that, if infiltrated, would indicate non‐resectability of the tumor according to the ESMO‐ESGO criteria. Surgical outcome, described by the surgeons at the end of the procedure, was used as the reference standard and non‐resectability was defined as the presence of residual disease > 1 cm or when debulking surgery was not feasible. The area under the receiver‐operating‐characteristics curve (AUC) and F 1  score were used to assess the performance of the preoperative imaging methods and surgical exploration in discriminating between patients with resectable and those with non‐resectable disease, based on the ESMO‐ESGO criteria. We also calculated the percentage agreement between imaging findings and surgical exploration findings at the start of surgery, supplemented when applicable by biopsy or follow‐up imaging for extra‐abdominal locations, regarding the presence of tumor infiltration at each of the eight anatomical sites associated with non‐resectability. Results Of 279 patients enrolled during the study period, 242 were included in the final analysis. In the subgroup of 167 patients who underwent surgery and had been examined by all three imaging methods, the AUC of the three imaging modalities and surgical exploration for discriminating between resectable and non‐resectable disease based on the ESMO‐ESGO criteria was 0.835 (95% CI, 0.756–0.915) for ultrasound, for CT it was 0.754 (95% CI, 0.664–0.843), for WB‐DWI/MRI it was 0.720 (95% CI, 0.626–0.814) and for surgical exploration it was 0.952 (95% CI, 0.915–0.988). Ultrasound was not inferior to CT or WB‐DWI/MRI, based on the AUC and F 1 score, in discriminating between patients with resectable and those with non‐resectable tubo‐ovarian carcinoma. At surgical exploration, at least one non‐resectability criterion was present in 32.2% cases. The criteria observed most frequently at surgical exploration were small‐bowel involvement (23.6% of cases), diffuse deep infiltration of the root of the small‐bowel mesentery (18.2% of cases) and hepatic hilum involvement (5.4% of cases). The percentage agreement between ultrasound and surgical exploration in assessing the presence of disease in at least one of the eight anatomical sites that, if infiltrated, would indicate non‐resectability of tumor, was 83.9%, surpassing the percentage agreement with surgical exploration of both CT (77.7%) and WB‐DWI/MRI (75.8%). Conclusion When performed by an experienced examiner, ultrasound is not inferior to either CT or WB‐DWI/MRI in discriminating between resectable and non‐resectable disease in patients with tubo‐ovarian carcinoma, based on evaluation of the presence of the disease in at least one of eight anatomical sites that, if infiltrated, would indicate non‐resectability of the tumor. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA‐1 multinomial regression model: validation study

ABSTRACTObjectivesTo assess the ability of the International Endometrial Tumor Analysis (IETA)‐1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding.MethodsThis was a retrospective study, in which we validated the IETA‐1 model on the IETA‐3 study cohort (n = 1745). The IETA‐3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow‐up of non‐endometrial pathology, in the work‐up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow‐up of at least 1 year if endometrial sampling was not performed. The IETA‐1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non‐uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver‐operating‐characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio).ResultsThe median age of the women in the IETA‐3 cohort was 51 (range, 20–85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA‐1 model had an AUC of 0.81 (95% CI, 0.73–0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32–0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62–0.73) (n = 1532). The IETA‐1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95–0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75–0.91), compared with 0.62 (95% CI, 0.52–0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08–0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA‐1 model gave an AUC of 0.81 (95% CI, 0.71–0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60–0.81) (difference in AUC, 0.11; 95% CI, 0.01–0.20).ConclusionThe IETA‐1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging Study in Advanced Ovarian Cancer

The aim of the study is the assessment of tumour sites critical for the achievement of optimal cytoreduction in patients with advanced ovarian cancer using Ultrasound, CT and WB-DWI/MRI. The study uses an equivalence design with a hypothesis that cases with non-resectable disease identified by Index test (Ultrasound, CT and WB-DWI MRI) are equivalent to a portion of cases identified during surgery.