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

OBJECTIVES: To 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. METHODS: This 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). RESULTS: The 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). CONCLUSION: The 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.

Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort.

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification.

OBJECTIVE: Despite its generally favorable prognosis at primary diagnosis, recurrence of endometrial cancer remains an important clinical challenge. The aim of this study was to analyze the value of molecular classification in recurrent endometrial cancer. METHODS: This study included patients with recurrent endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort) with molecular classification of the primary tumor. RESULTS: Out of 594 molecularly classified endometrial cancer patients, 101 patients experienced recurrence, consisting of 2 POLEmut, 33 MMRd, 30 p53abn, and 36 NSMP tumors. Mean age at recurrence was 71 years and mean follow-up was 54 months. Overall, median time to first recurrence was 16 months (95% CI 12-20); with the shortest median time in MMRd patients, with 13 months (95% CI 5-21). The pattern of recurrence was distinct among molecular subgroups: MMRd tumors experienced more locoregional, while p53abn cases showed more abdominal recurrences (P = .042). Median survival after recurrence was best for MMRd cases (43 months, 95% CI 11-76), compared to 39 months (95% CI 21-57) and 10 months (95% CI 7-13) for the NSMP and p53abn cases respectively (log-rank, P = .001). CONCLUSION: Molecular classification is a significant indicator of survival after recurrence in endometrial cancer patients, and patterns of recurrence differ by molecular subgroups. While MMRd endometrial cancer show more locoregional recurrence and the best survival rates after recurrence, p53abn patients experience abdominal recurrence more often and had the worst prognosis of all recurrent patients.

Imaging in gynecological disease (24): clinical and ultrasound characteristics of ovarian mature cystic teratomas.

OBJECTIVE: To describe the clinical and ultrasound features of ovarian mature cystic teratomas (MCTs). METHODS: This was a retrospective study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histologically confirmed diagnosis of MCT who had undergone transvaginal ultrasound examination between 1999 and 2016 (IOTA phases 1, 2, 3 and 5) in one of five centers. Ultrasound was performed by an experienced examiner who used the standardized IOTA examination technique and terminology. In addition to extracting data from the IOTA database, available two-dimensional grayscale and color or power Doppler images were reviewed retrospectively to identify typical ultrasound features of MCT described previously and detect possible new features using pattern recognition. All images were reviewed by two independent examiners and further discussed with two ultrasound experts to reach consensus. RESULTS: Included in the study were 454 patients with histologically confirmed MCT. Median age was 33 (range, 8-90) years and 66 (14.5%) patients were postmenopausal. Most MCTs were described by the original ultrasound examiner as unilocular (262/454 (57.7%)) or multilocular (70/454 (15.4%)) cysts with mixed echogenicity of cystic fluid (368/454 (81.1%)), acoustic shadowing (328/454 (72.2%)) and no or little vascularization on color Doppler (color score 1, 240/454 (52.9%); color score 2, 123/454 (27.1%)). The median largest lesion diameter was 66 (range, 15-310) mm. A correct preoperative diagnosis of MCT was suggested by the original ultrasound examiner in 372/454 (81.9%) cases. On retrospective review of ultrasound images of 334 MCTs that had quality sufficient for assessment, 'dots and/or lines' and/or 'echogenic white ball' (typical features according to the literature) were present in 271/334 (81.1%) masses. We identified four new ultrasound features characteristic of MCT: 'cotton wool tufts', 'mushroom cap sign', 'completely hyperechogenic lesion' and 'starry sky sign'. At least one classical or novel ultrasound feature was present in 315/334 (94.3%) MCTs. Twenty-nine (8.7%) MCTs manifested vascularized solid tissue, of which seven exhibited no typical features. CONCLUSION: We provide a comprehensive overview of conventional and newly described ultrasound features of MCTs. Only a small proportion of MCTs did not manifest any of the typical features. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound features of endometrial pathology in women without abnormal uterine bleeding: results from the International Endometrial Tumor Analysis study (IETA3).

OBJECTIVES: The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB. METHODS: This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology. RESULTS: In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized. CONCLUSIONS: We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (23): clinical and ultrasound characteristics of ovarian carcinosarcoma.

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma. METHODS: This was a retrospective multicenter study. Patients with a histological diagnosis of ovarian carcinosarcoma, who had undergone preoperative ultrasound examination between 2010 and 2019, were identified from the International Ovarian Tumor Analysis (IOTA) database. Additional patients who were examined outside of the IOTA study were identified from the databases of the participating centers. The masses were described using the terms and definitions of the IOTA group. Additionally, two experienced ultrasound examiners reviewed all available images to identify typical ultrasound features using pattern recognition. RESULTS: Ninety-one patients with ovarian carcinosarcoma who had undergone ultrasound examination were identified, of whom 24 were examined within the IOTA studies and 67 were examined outside of the IOTA studies. Median age at diagnosis was 66 (range, 33-91) years and 84/91 (92.3%) patients were postmenopausal. Most patients (67/91, 73.6%) were symptomatic, with the most common complaint being pain (51/91, 56.0%). Most tumors (67/91, 73.6%) were International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV. Bilateral lesions were observed on ultrasound in 46/91 (50.5%) patients. Ascites was present in 38/91 (41.8%) patients. The median largest tumor diameter was 100 (range, 18-260) mm. All ovarian carcinosarcomas contained solid components, and most were described as solid (66/91, 72.5%) or multilocular-solid (22/91, 24.2%). The median diameter of the largest solid component was 77.5 (range, 11-238) mm. Moderate or rich vascularization was found in 78/91 (85.7%) cases. Retrospective analysis of ultrasound images and videoclips using pattern recognition in 73 cases revealed that all tumors had irregular margins and inhomogeneous echogenicity of the solid components. Forty-seven of 73 (64.4%) masses appeared as a solid tumor with cystic areas. Cooked appearance of the solid tissue was identified in 28/73 (38.4%) tumors. No pathognomonic ultrasound sign of ovarian carcinosarcoma was found. CONCLUSIONS: Ovarian carcinosarcomas are usually diagnosed in postmenopausal women and at an advanced stage. The most common ultrasound appearance is a large solid tumor with irregular margins, inhomogeneous echogenicity of the solid tissue and cystic areas. The second most common pattern is a large multilocular-solid mass with inhomogeneous echogenicity of the solid tissue. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound image analysis using deep neural networks for discriminating between benign and malignant ovarian tumors: comparison with expert subjective assessment.

OBJECTIVES: To develop and test the performance of computerized ultrasound image analysis using deep neural networks (DNNs) in discriminating between benign and malignant ovarian tumors and to compare its diagnostic accuracy with that of subjective assessment (SA) by an ultrasound expert. METHODS: We included 3077 (grayscale, n = 1927; power Doppler, n = 1150) ultrasound images from 758 women with ovarian tumors, who were classified prospectively by expert ultrasound examiners according to IOTA (International Ovarian Tumor Analysis) terms and definitions. Histological outcome from surgery (n = 634) or long-term (≥ 3 years) follow-up (n = 124) served as the gold standard. The dataset was split into a training set (n = 508; 314 benign and 194 malignant), a validation set (n = 100; 60 benign and 40 malignant) and a test set (n = 150; 75 benign and 75 malignant). We used transfer learning on three pre-trained DNNs: VGG16, ResNet50 and MobileNet. Each model was trained, and the outputs calibrated, using temperature scaling. An ensemble of the three models was then used to estimate the probability of malignancy based on all images from a given case. The DNN ensemble classified the tumors as benign or malignant (Ovry-Dx1 model); or as benign, inconclusive or malignant (Ovry-Dx2 model). The diagnostic performance of the DNN models, in terms of sensitivity and specificity, was compared to that of SA for classifying ovarian tumors in the test set. RESULTS: At a sensitivity of 96.0%, Ovry-Dx1 had a specificity similar to that of SA (86.7% vs 88.0%; P = 1.0). Ovry-Dx2 had a sensitivity of 97.1% and a specificity of 93.7%, when designating 12.7% of the lesions as inconclusive. By complimenting Ovry-Dx2 with SA in inconclusive cases, the overall sensitivity (96.0%) and specificity (89.3%) were not significantly different from using SA in all cases (P = 1.0). CONCLUSION: Ultrasound image analysis using DNNs can predict ovarian malignancy with a diagnostic accuracy comparable to that of human expert examiners, indicating that these models may have a role in the triage of women with an ovarian tumor. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Análisis de imágenes ecográficas utilizando redes neurales profundas para distinguir entre tumores ováricos benignos y malignos: comparación con la evaluación subjetiva de expertos OBJETIVOS: Desarrollar y probar el desempeño del análisis de imágenes ecográficas computarizadas utilizando redes neurales profundas (RNP) para distinguir entre tumores ováricos benignos y malignos y comparar su precisión en el diagnóstico con la de la evaluación subjetiva (ES) por especialistas expertos en ecografía. MÉTODOS: Se incluyeron 3077 (escala de grises, n=1927; power Doppler, n=1150) imágenes de ultrasonido de 758 mujeres con tumores ováricos, que fueron clasificadas prospectivamente por examinadores especialistas en ecografía, de acuerdo con los términos y definiciones de la IOTA (Análisis Internacional de Tumores Ováricos). El resultado histológico de la cirugía (n=634) o el seguimiento a largo plazo (≥3 años) (n=124) sirvieron como el estándar de referencia. El conjunto de datos se dividió en un subconjunto de formación (n=508; 314 benignos y 194 malignos), un subconjunto de validación (n=100; 60 benignos y 40 malignos) y un subconjunto de pruebas (n=150; 75 benignos y 75 malignos). Se utilizó el aprendizaje de transferencia en tres RNP pre-formadas: VGG16, ResNet50 y MobileNet. Cada modelo fue formado primero mediante escalas de temperatura, al igual que los la calibración de los outputs. A continuación, se utilizó una combinación de los tres modelos para estimar la probabilidad de que el tumor fuera maligno con base en la totalidad de las imágenes de un caso determinado. La combinación de RNP permitió clasificar los tumores como benignos o malignos (modelo Ovry-Dx1); o como benignos, no concluyentes o malignos (modelo Ovry-Dx2). Se comparó el desempeño para el diagnóstico de los modelos de RNP, en términos de sensibilidad y de especificidad, con el de la ES para la clasificación de los tumores ováricos en el subconjunto de formación. RESULTADOS: Con una sensibilidad del 96,0%, Ovry-Dx1 tuvo una especificidad similar a la de la ES (86,7% frente a 88,0%; P=1,0). Ovry-Dx2 tuvo una sensibilidad del 97,1% y una especificidad del 93,7%, y designaron un 12,7% de las lesiones como no concluyentes. Cuando se complementó Ovry-Dx2 con ES en los casos no concluyentes, la sensibilidad general (96,0%) y la especificidad (89,3%) no fueron significativamente diferentes de la utilización de ES en todos los casos (P=1,0). CONCLUSIÓN: El análisis de imágenes ecográficas mediante RNP puede predecir el cáncer de ovario con una precisión en el diagnóstico igual a la de los especialistas expertos humanos, lo que indica que estos modelos pueden jugar un papel en el triaje de mujeres con un tumor de ovario. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Combination of Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) with sonographic and demographic characteristics in preoperative prediction of recurrence or progression of endometrial cancer.

OBJECTIVE: To evaluate the ability of demographic and sonographic variables and the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) classification to predict preoperatively tumor recurrence or progression in women with endometrial cancer. METHODS: The study included 339 women with histologically confirmed endometrial cancer who underwent expert transvaginal ultrasound in a single center before surgery as part of the prospective International Endometrial Tumor Analysis 4 study or who were evaluated using the same protocol. The tumors were classified according to histotype, FIGO (International Federation of Gynecology and Obstetrics) grade and FIGO stage. In addition, molecular analysis was performed for classification into the four ProMisE subtypes: polymerase-ϵ exonuclease domain mutations (POLE EDM), mismatch repair proteins deficiency (MMR-D), protein 53 wild type (p53 wt) and protein 53 abnormal (p53 abn). Demographic and preoperative sonographic characteristics, tumor recurrence or progression and survival were compared between the ProMisE subgroups. Cox regression analysis was used to identify prognostic factors associated with recurrence or progression, using univariable models to study crude associations and multivariable models to study adjusted associations. Logistic regression and receiver-operating-characteristics (ROC)-curve analysis were used to assess the predictive ability of the preoperative prognostic factors regarding recurrence or progression of cancer within 3 years after surgery, and to compare their predictive ability to that of the European Society for Medical Oncology (ESMO) preoperative (based on depth of myometrial invasion, histotype and grade) and postoperative (based on histotype, grade, surgical stage and lymphovascular space invasion) risk classifications. In a separate subanalysis, cases were stratified according to ProMisE p53 abn status (present vs absent) and sonographic tumor size (anteroposterior (AP) diameter < 2 cm vs ≥ 2 cm). RESULTS: Median follow-up time from surgery was 58 months (interquartile range, 48-71 months; range, 0-102 months). Recurrence or progression of cancer occurred in 51/339 (15%) women, comprising 14% of those with MMR-D, 8% of those with POLE EDM, 9% of those with p53 wt and 45% of those with p53 abn ProMisE subtype. On multivariable analysis, age, waist circumference, ProMisE subtype and tumor extension and AP diameter on ultrasound were associated with tumor recurrence or progression. A multivariable model comprising ProMisE subtype, age, waist circumference and sonographic tumor extension and size (area under the ROC curve (AUC), 0.89 (95% CI, 0.85-0.93)) had comparable ability to predict tumor recurrence/progression to that of a multivariable model comprising histotype, grade, age, waist circumference and sonographic tumor extension and size (AUC, 0.88 (95% CI, 0.83-0.92)), and better predictive ability than both the preoperative (AUC, 0.74 (95% CI, 0.67-0.82); P < 0.01) and postoperative (AUC, 0.79 (95% CI, 0.72-0.86); P < 0.01) ESMO risk classifications. Women with a combination of non-p53 abn subtype and tumor size < 2 cm (164/339 (48%)) had a very low risk (1.8%) of tumor recurrence or progression. CONCLUSIONS: The combination of demographic characteristics, sonographic findings and ProMisE subtype had better preoperative predictive ability for tumor recurrence or progression than did the ESMO classification, supporting their use in the preoperative risk stratification of women with endometrial cancer. The combination of p53 status with ultrasound tumor size has the potential to identify preoperatively a large group of women with a very low risk of recurrence or progression. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Terms, definitions and measurements to describe sonographic features of lymph nodes: consensus opinion from the Vulvar International Tumor Analysis (VITA) group.

In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Interobserver agreement of transvaginal ultrasound and magnetic resonance imaging in local staging of cervical cancer.

OBJECTIVE: To evaluate interobserver agreement for the assessment of local tumor extension in women with cervical cancer, among experienced and less experienced observers, using transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI). METHODS: The TVS observers were all gynecologists and consultant ultrasound specialists, six with and seven without previous experience in cervical cancer imaging. The MRI observers were five radiologists experienced in pelvic MRI and four less experienced radiology residents without previous experience in MRI of the pelvis. The less experienced TVS observers and all MRI observers underwent a short basic training session in the assessment of cervical tumor extension, while the experienced TVS observers received only a written directive. All observers were assigned the same images from cervical cancer patients at all stages (n = 60) and performed offline evaluation to answer the following three questions: (1) Is there a visible primary tumor? (2) Does the tumor infiltrate > ⅓ of the cervical stroma? and (3) Is there parametrial invasion? Interobserver agreement within the four groups of observers was assessed using Fleiss kappa (κ) with 95% CI. RESULTS: Experienced and less experienced TVS observers, respectively, had moderate interobserver agreement with respect to tumor detection (κ (95% CI), 0.46 (0.40-0.53) and 0.46 (0.41-0.52)), stromal invasion > ⅓ (κ (95% CI), 0.45 (0.38-0.51) and 0.53 (0.40-0.58)) and parametrial invasion (κ (95% CI), 0.57 (0.51-0.64) and 0.44 (0.39-0.50)). Experienced MRI observers had good interobserver agreement with respect to tumor detection (κ (95% CI), 0.70 (0.62-0.78)), while less experienced MRI observers had moderate agreement (κ (95% CI), 0.51 (0.41-0.62)), and both experienced and less experienced MRI observers, respectively, had good interobserver agreement regarding stromal invasion (κ (95% CI), 0.80 (0.72-0.88) and 0.71 (0.61-0.81)) and parametrial invasion (κ (95% CI), 0.69 (0.61-0.77) and 0.71 (0.61-0.81)). CONCLUSIONS: We found interobserver agreement for the assessment of local tumor extension in patients with cervical cancer to be moderate for TVS and moderate-to-good for MRI. The level of interobserver agreement was associated with experience among TVS observers only for parametrial invasion. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (22): clinical and ultrasound characteristics of ovarian embryonal carcinomas, non-gestational choriocarcinomas and malignant mixed germ cell tumors.

OBJECTIVE: To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor. METHODS: This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition. RESULTS: One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14-77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38-216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours. CONCLUSIONS: A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Vessel morphology depicted by three-dimensional power Doppler ultrasound as second-stage test in adnexal tumors that are difficult to classify: prospective diagnostic accuracy study.

OBJECTIVES: To assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second-stage test in adnexal masses that are difficult to classify. METHODS: This was a prospective observational international multicenter diagnostic accuracy study. Consecutive patients with an adnexal mass underwent standardized transvaginal two-dimensional (2D) grayscale and color or power Doppler and 3D power Doppler ultrasound examination by an experienced examiner, and those with a 'difficult' tumor were included in the current analysis. A difficult tumor was defined as one in which the International Ovarian Tumor Analysis (IOTA) logistic regression model-1 (LR-1) yielded an ambiguous result (risk of malignancy, 8.3% to 25.5%), or as one in which the ultrasound examiner was uncertain regarding classification as benign or malignant when using subjective assessment. Even when the ultrasound examiner was uncertain, he/she was obliged to classify the tumor as most probably benign or most probably malignant. For each difficult tumor, one researcher created a 360° rotating 3D power Doppler image of the vessel tree in the whole tumor and another of the vessel tree in a 5-cm3 spherical volume selected from the most vascularized part of the tumor. Two other researchers, blinded to the patient's history, 2D ultrasound findings and histological diagnosis, independently described the vessel tree using predetermined vessel features. Their agreed classification was used. The reference standard was the histological diagnosis of the mass. The sensitivity of each test for discriminating between benign and malignant difficult tumors was plotted against 1 - specificity on a receiver-operating-characteristics diagram, and the test with the point furthest from the reference line was considered to have the best diagnostic ability. RESULTS: Of 2403 women with an adnexal mass, 376 (16%) had a difficult mass. Ultrasound volumes were available for 138 of these cases. In 79/138 masses, the ultrasound examiner was uncertain about the diagnosis based on subjective assessment, in 87/138, IOTA LR-1 yielded an ambiguous result and, in 28/138, both methods gave an uncertain result. Of the masses, 38/138 (28%) were malignant. Among tumors that were difficult to classify as benign or malignant by subjective assessment, the vessel feature 'densely packed vessels' had the best discriminative ability (sensitivity 67% (18/27), specificity 83% (43/52)) and was slightly superior to subjective assessment (sensitivity 74% (20/27), specificity 60% (31/52)). In tumors in which IOTA LR-1 yielded an ambiguous result, subjective assessment (sensitivity 82% (14/17), specificity 79% (55/70)) was superior to the best vascular feature, i.e. changes in the diameter of vessels in the whole tumor volume (sensitivity 71% (12/17), specificity 69% (48/70)). CONCLUSION: Vessel morphology depicted by 3D power Doppler ultrasound may slightly improve discrimination between benign and malignant adnexal tumors that are difficult to classify by subjective ultrasound assessment. For tumors in which the IOTA LR-1 model yields an ambiguous result, subjective assessment is superior to vessel morphology as a second-stage test. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding.

OBJECTIVE: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. RESULTS: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m2 (range, 16.0-72.1 kg/m2 ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2-1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6-3.4%)) cases with a single vessel without branching on unenhanced ultrasound. CONCLUSIONS: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Sonographic characteristics of post-molar gestational trophoblastic neoplasia at diagnosis and during follow-up, and relationship with methotrexate resistance.

OBJECTIVES: To describe the sonographic characteristics of post-molar gestational trophoblastic neoplasia (GTN) at diagnosis and during follow-up, and to assess their association with methotrexate (MTX) resistance (R) as first-line chemotherapy. METHODS: This was a retrospective study of all women treated for post-molar GTN at Karolinska University Hospital, Stockholm, Sweden, between October 2010 and December 2017, who had undergone expert transvaginal ultrasound assessment ≤ 2 weeks prior to, or ≤ 1 week after, the start of first-line MTX treatment. Women with a detectable uterine lesion were followed up with repeat scans during treatment, as well as after treatment in cases of persistent lesions. The association between MTX-R and sonographic findings at inclusion was assessed. RESULTS: Of 47 eligible women, 36 were included in the analysis after excluding those who had not undergone structured transvaginal ultrasound assessment and those who started treatment at another center. The median age at diagnosis was 33 (interquartile range (IQR), 27-43) years and 35/36 (97%) women were in the FIGO low-risk group (risk score, 0-6). At inclusion, no uterine lesions were found in eight (22%) women, focal lesions in 24 (67%) women and global lesions in four (11%) women. Median maximum lesion diameter was 40.4 (IQR, 31.3-49.4) mm and 26/28 (93%) lesions had a color score of 3 or 4. Arteriovenous fistulas were found in 9/28 (32%) women and theca lutein cysts in 4/36 (11%) women. Four women with GTN lesion at inclusion underwent hysterectomy prior to the first follow-up ultrasound scan and a fifth woman with a growing lesion underwent hysterectomy, which revealed persistent viable trophoblastic tissue. All remaining women reached complete remission and median time to human chorionic gonadotropin normalization was 2.7 (IQR, 1.4-3.7) months. During ultrasound follow-up, 88% (21/24) of lesions resolved completely. Two women with a persisting lesion remained in complete remission. Median time to disappearance of vascularity was 5.8 (IQR, 3.7-9.3) months and median time to resolution of the lesion was 6.8 (IQR, 3.7-9.3) months. MTX-R developed in 12/31 (39%) women. Uterine tumors ≥ 4 cm (73% vs 17%; P = 0.008) and global lesions (25% vs 0%; P = 0.03) were significantly more common in women with compared to those without MTX-R. CONCLUSION: Uterine lesions were detected at the time of diagnosis in 78% of women with post-molar GTN. The vast majority of the lesions resolved completely during follow-up, after a median of 7 months. MTX-R was more common in uterine tumors of 4 cm, or larger, and in global lesions. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Dynamic contrast-enhanced ultrasound improves diagnostic performance in endometrial cancer staging.

OBJECTIVES: To compare the sensitivity and specificity of conventional two-dimensional transvaginal ultrasound/power Doppler (2D-TVU/PD) alone and 2D-TVU/PD combined with dynamic contrast-enhanced ultrasound (DCE-US) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) in women with endometrial cancer (EC), and to assess the association of DCE-US semiquantitative and qualitative variables with International Federation of Gynecology and Obstetrics (FIGO) Stage ≥ IB and 'high-risk' cancer. METHODS: This was a prospective study of 101 consecutive women with biopsy-confirmed EC, undergoing expert ultrasound examination at Karolinska University Hospital, a tertiary referral center. All consenting women underwent DCE-US using a 1.5-2.5-mL intravenous bolus of SonoVue contrast agent, as well as conventional 2D-TVU/PD examination. DCE-US videoclips were analyzed with regard to filling (global or focal), wash-in (prior, simultaneous or after) and wash-out (global or focal) patterns of the contrast agent in the tumor compared with the surrounding tissue, as well as semiquantitative DCE-US parameters (wash-in slope, time-to-peak, peak intensity and area under the time-intensity curve (TIC)) obtained from a TIC. The study cohort was compared with a control cohort of women with EC examined at our center according to the International Endometrial Tumor Analysis protocol using 2D-TVU/PD only, matched at a ratio of 3:1 for FIGO stage and grade. The sensitivity and specificity of 2D-TVU/PD alone in the control cohort and in combination with DCE-US in the study cohort in the diagnosis of deep MI, CSI and high-risk cancer (defined as FIGO Stage ≥ IB and/or Grade 3 endometrioid and/or non-endometrioid histology) were compared, using pathological evaluation after hysterectomy as the 'gold standard'. RESULTS: After exclusions, 93 women were included in the study cohort and were matched to 279 women in the control cohort. The prevalence of FIGO Stage IA, Grade 1-2 EC was 52% in both cohorts. The sensitivity of 2D-TVU/PD with DCE-US in the study cohort was higher than that of 2D-TVU/PD alone in the control cohort in diagnosing both deep MI (0.74 vs 0.62; P = 0.036) and CSI (0.75 vs 0.51; P < 0.001), whereas the specificity was not significantly different (0.87 vs 0.85 and 0.96 vs 0.95, respectively). Compared with 2D-TVU/PD alone, the specificity of 2D-TVU/PD with DCE-US was higher in detecting high-risk cancer (0.94 vs 0.85; P = 0.024) but the sensitivity did not differ (0.73 vs 0.71). High-risk cancer and FIGO Stage ≥ IB were characterized by a 'focal' filling pattern, with a 'prior' wash-in pattern and a 'focal' wash-out pattern on subjective assessment of DCE-US videoclips. All semiquantitative DCE-US parameters were significantly predictive of FIGO Stage ≥ IB but not of high-risk cancer, despite a clear trend. CONCLUSIONS: Compared with 2D-TVU/PD alone, combining 2D-TVU/PD with DCE-US can significantly improve the detection of deep MI and CSI in women with EC, without increasing the false-positive rate. It can also improve the correct classification of high-risk disease, mainly by increasing specificity, thereby possibly reducing the number of unnecessarily extensive surgeries by almost 10%. Semiquantitative DCE-US parameters, as well as a 'focal' filling pattern, endometrial wash-in prior to the myometrium and a 'focal' wash-out pattern, are all associated with more advanced disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (17): ultrasound features of malignant ovarian yolk sac tumors (endodermal sinus tumors).

OBJECTIVE: To describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs). METHODS: In this retrospective multicenter study, we included 21 patients with a histological diagnosis of ovarian YST and available transvaginal ultrasound images and/or videoclips and/or a detailed ultrasound report. Ten patients identified from the International Ovarian Tumor Analysis (IOTA) studies had undergone a standardized preoperative ultrasound examination, by an experienced ultrasound examiner, between 1999 and 2016. A further 11 patients were identified through medical files, for whom ultrasound images were retrieved from local image workstations and picture archiving and communication systems. All tumors were described using IOTA terminology. The collected ultrasound images and videoclips were used by two observers for additional characterization of the tumors. RESULTS: All cases were pure YSTs, except for one that was a mixed tumor (80% YST and 20% embryonal carcinoma). Median age at diagnosis was 25 (interquartile range (IQR), 19.5-30.5) years. Seventy-six percent (16/21) of women had an International Federation of Gynecology and Obstetrics (FIGO) Stage I-II tumor at diagnosis. Fifty-eight percent (11/19) of women felt pain during the ultrasound examination and one presented with ovarian torsion. Median serum α-fetoprotein (S-AFP) level was 4755 (IQR, 1071-25 303) µg/L and median serum CA 125 level was 126 (IQR, 35-227) kU/L. On ultrasound assessment, 95% (20/21) of tumors were unilateral. The median maximum tumor diameter was 157 (IQR, 107-181) mm and the largest solid component was 110 (IQR, 66-159) mm. Tumors were classified as either multilocular-solid (10/21; 48%) or solid (11/21; 52%). Papillary projections were found in 10% (2/21) of cases. Most (20/21; 95%) tumors were well vascularized (color score, 3-4) and none had acoustic shadowing. Malignancy was suspected in all cases, except in the patient with ovarian torsion, who presented a tumor with a color score of 1, which was classified as probably benign. Image and videoclip quality was considered as adequate in 18/21 cases. On review of the images and videoclips, we found that all tumors contained both solid components and cystic spaces, and that 89% (16/18) had irregular, still fine-textured and slightly hyperechoic solid tissue, giving them a characteristic appearance. CONCLUSION: Malignant ovarian YSTs are often detected at an early stage, in young women usually in the second or third decade of life, presenting with pain and markedly elevated S-AFP. On ultrasound, malignant ovarian YSTs are mostly unilateral, large and multilocular-solid or solid, with fine-textured slightly hyperechoic solid tissue and rich vascularization. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology..

Imaging in gynecological disease (20): clinical and ultrasound characteristics of adnexal torsion.

OBJECTIVES: To describe the clinical and ultrasound characteristics of adnexal torsion. METHODS: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ. RESULTS: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1-88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30-349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion. CONCLUSION: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (19): clinical and ultrasound features of extragastrointestinal stromal tumors (eGIST).

OBJECTIVE: To describe the clinical and sonographic characteristics of extragastrointestinal stromal tumors (eGISTs). METHODS: This was a retrospective multicenter study. The data of patients with a histological diagnosis of eGIST who had undergone preoperative ultrasound examination were retrieved from the databases of nine large European gynecologic oncology centers. One investigator from each center reviewed stored images and ultrasound reports, and described the lesions using the terminology of the International Ovarian Tumor Analysis and Morphological Uterus Sonographic Assessment groups, following a predefined ultrasound evaluation form. Clinical, surgical and pathological information was also recorded. RESULTS: Thirty-five women with an eGIST were identified; in 17 cases, the findings were incidental, and 18 cases were symptomatic. Median age was 57 years (range, 21-85 years). Tumor marker CA 125 was available in 23 (65.7%) patients, with a median level of 23 U/mL (range, 7-403 U/mL). The vast majority of eGISTs were intraperitoneal lesions (n = 32 (91.4%)); the remaining lesions were retroperitoneal (n = 2 (5.7%)) or preperitoneal (n = 1 (2.9%)). The most common site of the tumor was the abdomen (n = 23 (65.7%)), and less frequently the pelvis (n = 12 (34.3%)). eGISTs were typically large (median largest diameter, 79 mm) solid (n = 31 (88.6%)) tumors, and were less frequently multilocular-solid tumors (n = 4 (11.4%)). The echogenicity of solid tumors was uniform in 8/31 (25.8%) cases, which were all hypoechogenic. Twenty-three solid eGISTs were non-uniform, either with mixed echogenicity (9/23 (39.1%)) or with cystic areas (14/23 (60.9%)). The tumor shape was mainly lobular (n = 19 (54.3%)) or irregular (n = 10 (28.6%)). Tumors were typically richly vascularized (color score of 3 or 4, n = 31 (88.6%)) with no shadowing (n = 31 (88.6%)). Based on pattern recognition, eGISTs were usually correctly classified as a malignant lesion in the ultrasound reports (n = 32 (91.4%)), and the specific diagnosis of eGIST was the most frequent differential diagnosis (n = 16 (45.7%)), followed by primary ovarian cancer (n = 5 (14.3%)), lymphoma (n = 2 (5.7%)) and pedunculated uterine fibroid (n = 2 (5.7%)). CONCLUSIONS: On ultrasound, eGISTs were usually solid, non-uniform pelvic or abdominal lobular tumors of mixed echogenicity, with or without cystic areas, with rich vascularization and no shadowing. The presence of a tumor with these features, without connection to the bowel wall, and not originating from the uterus or adnexa, is highly suspicious for eGIST. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Validation of ultrasound strategies to assess tumor extension and to predict high-risk endometrial cancer in women from the prospective IETA (International Endometrial Tumor Analysis)-4 cohort.

OBJECTIVES: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). METHODS: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. RESULTS: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver-operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. CONCLUSIONS: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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

OBJECTIVE: To 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. METHODS: A 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). RESULTS: Lymphadenectomy 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. CONCLUSIONS: Based 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.