{"paper_id":"8124c9cf-72b1-4cda-81bd-595a7637384b","body_text":"Adnexal masses are common findings in clinical practice ( 1 , 2 ) . The vast majority of adnexal masses are\nbenign, malignant masses accounting for only a small proportion ( 3 , 4 ) . In 2020, the estimated number of cases\nof ovarian cancer worldwide was only 313,000 ( 5 ) . Excluding malignancy of an adnexal mass\nthrough preoperative examinations is crucial for proper screening and treatment\nplanning. It is recommended that a woman with a suspicious adnexal mass be referred\nto a surgeon specializing in gynecologic oncology ( 6 ) .\nIn most cases, screening for the risk of malignancy of an adnexal mass can be\nperformed effectively by transvaginal ultrasound and the use of targeted algorithms,\nespecially if the simple rules established by the International Ovarian Tumor\nAnalysis (IOTA) group are applied ( 7 , 8 ) .\nHowever, approximately 20% of adnexal masses are considered indeterminate on\nultrasound ( 9 , 10 ) .\nAdnexal masses that are considered indeterminate represent a dilemma for the entire\nteam that treats the affected patient, because such patients are at risk of\nunnecessary surgery. However, if the watchful waiting approach is adopted, the\n“window” of opportunity to diagnose cancer at an early stage may be missed. There is\nalso a risk that the patient will be subjected to a surgical procedure performed by\na non-specialist, if there is a false-negative test result or a lesion of\nnon-ovarian origin ( 6 , 11 ) . According to the European Society of Urogenital\nRadiology ( 12 , 13 ) , magnetic resonance imaging (MRI) of the pelvis is\nindicated to assess an adnexal tumor that is considered indeterminate on\ntransvaginal ultrasound.\nIn 2013, Thomassin-Naggara et al. ( 14 )  presented a diagnostic algorithm for adnexal lesions\nthat combines morphological features and functional MRI aspects to assign a\nnumerical score. The system was initially called the ADNEX MR SCORING system and had\nfive distinct categories (corresponding to scores from 1 to 5): categories 1, 2, and\n3 were related to (probably) benign masses; and categories 4 and 5 were related to\nadnexal masses considered indeterminate or suspicious for malignancy. At cutoff\nscores of 4 and 5, the score had excellent accuracy (with a sensitivity of 93.5% and\na specificity of 96.6%) for the detection of malignancy in an adnexal\nmass ( 14 ) .\nHowever, some technical aspects, such as the time-intensity of dynamic\ncontrast-enhanced (DCE) studies of contrast-enhanced sequences (perfusion studies),\nwhich constituted one of the central elements of the ADNEX MR SCORING system, likely\nwould have limited its use on a larger scale ( 15 ) . Studies have shown that it is possible\nto use less complex contrast-enhanced sequences, with no loss of\naccuracy ( 16 ) .\nRecently, the ADNEX MR SCORING system was validated in a large prospective\nmulticenter study conducted by the original authors ( 17 ) ; some MRI aspects and parameters were\nimproved, after which the score was adopted by the American College of Radiology, at\nwhich point it was renamed the Ovarian-Adnexal Reporting and Data System MRI (O-RADS\nMRI) score ( 18 , 19 ) . Some modifications\nwere made; the new score incorporated the possibility of using lower temporal\nresolution in the DCE studies and even of performing a visual analysis of the\nenhancement pattern when a DCE study is not feasible ( 18 ) .\nThe O-RADS MRI score was designed to simplify and standardize the reporting of MRI of\nadnexal masses, in order to provide the clinician with the information necessary for\nthe most appropriate management of patients, similar to the Breast Imaging Reporting\nand Data System, the result of which is linked to the clinical management of breast\nlesions ( 20 ) . In the O-RADS MRI score ( 18 ) , the absence of a suspicious adnexal\nlesion receives a score of 1; an adnexal lesion that is almost certainly benign\nreceives a score of 2; a low-risk lesion receives a score of 3; an intermediate-risk\nlesion receives a score of 4; and a high-risk lesion receives a score of 5. In their\nsubsequent study, Thomassin-Naggara et al. ( 17 )  found that, for the detection of malignancy, a\nscore of 4 or 5 had a sensitivity of 93.0% (95% CI: 89-96) and a specificity of\n91.0% (95% CI: 89-93).\nIn this article, we evaluate the accuracy of the O-RADS MRI for evaluating adnexal\nmasses in a large sample of lesions. We also provide technical notes on the updates\nin relation to the original score ( 14 ) .\n\nThis was a prospective study conducted at the Centro de Atenção\nIntegral à Saúde da Mulher/Hospital da Mulher Prof. Dr. J. A. Pinotti,\na tertiary cancer center operated by the Faculdade de Ciências Médicas\nda Universidade Estadual de Campinas (Unicamp), in the city of Campinas, SP, Brazil.\nThe study was approved by the Unicamp Research Ethics Committee (Reference nos.\n1092/2009 and 008/2010). All participating patients gave written informed\nconsent.\nWe randomly recruited women who were referred to our hospital for investigation of an\nadnexal mass between February 2014 and December 2020. To avoid any selection biases,\nwe ensured that the recruiter had no knowledge of the clinical data (e.g., time of\nevolution), laboratory test results (serum levels of CA-125), or findings on imaging\n(pelvic ultrasound) for any given patient. An ultrasound evaluation of the pelvis\nwas scheduled for each of the women enrolled. After ultrasound, 257 cases were\nscheduled for MRI, which was performed at the Hospital Estadual Sumaré, in\nthe city of Sumaré, SP, Brazil, a Unicamp-affiliated hospital located near\nthe Hospital da Mulher Prof. Dr. J. A. Pinotti. When indicated, diagnostic or\ntherapeutic surgical procedures were performed. The indication for surgery was based\non the results of the clinical examination; preoperative biomarker levels; the\nultrasound findings, evaluated with the IOTA simple rules, as described by Timmerman\net al. ( 7 ) ; and the MRI\nresults (practitioners did not have access to MRI scoring results).  Figure 1  shows the patient selection process. Of\nthe 257 women initially enrolled, 14 were lost to follow-up. Therefore, data for 243\nwomen, with a total of 287 adnexal masses, were included in the study. Of the 169\npatients (with 190 adnexal masses) for whom a histological diagnosis was made, 62\nwere found to have a single malignant adnexal tumor, 14 were found to have bilateral\nmalignant adnexal tumors, 86 were found to have a single benign adnexal tumor, and 7\nwere found to have bilateral benign adnexal tumors. A team of pathologists\nspecializing in pelvic neoplasms made the final histological diagnosis, in\naccordance with the guidelines established by the WHO Classification of Tumours of\nFemale Reproductive Organs ( 21 ) . Of the 74 patients (with 97 adnexal masses) who did not\nundergo an invasive procedure and were followed to evaluate their clinical\nevolution, one had four adnexal masses, two had three adnexal masses, 16 had two\nadnexal masses, and 55 had a single adnexal mass. The last follow-up evaluation was\nin December 2020.\nFigure 1 Flow chart of the patient selection process.\nFlow chart of the patient selection process.\nThe MRI scans, surgical procedures, and histopathological analyses were performed at\nthe Hospital da Mulher Prof. Dr. J. A. Pinotti. More than one tumor was found in 40\nwomen, and the O-RADS MRI score was calculated for each mass separately, as\nsuggested by its authors ( 17 ) . All MRI assessments were performed before the\nhistological diagnosis was known or the decision for clinical follow-up had been\nmade.\nThe reference standard was the histopathological diagnosis in the adnexal masses\nsubmitted to surgery (n = 178) and in those submitted to percutaneous biopsy (n =\n12). For the adnexal masses not subjected to histopathological examination (n = 97),\nthe criteria for benign disease were based on clinical and imaging data obtained\nover a period of at least 12 months, following the usual clinical care protocols of\nthe institution.\nAll MRI scans were acquired in a 1.5-T scanner (Signa HDxt; GE Healthcare,\nMilwaukee, WI, USA) with a pelvic phased-array coil. Prior the MRI scans,\npatients fasted for 3 h. No antispasmodic agents were used; nor was vaginal or\nrectal contrast administered. We used a protocol aimed at assessing adnexal\nmasses, which consisted of T2-weighted multiplanar (axial, sagittal, and\ncoronal) sequences, in-phase and out-of-phase T1-weighted sequences,\ndiffusion-weighted sequences ( b  = 0, 500, and 1,000\ns/mm 2 ), and T1-weighted sequences, with and without fat\nsaturation, before and after intravenous contrast administration by power\ninjection at 3.5 mL/sec. The DCE study consisted of five sequential\nacquisitions, with an interval of 30 s between them and acquisition times\nranging from 10 s to 13 s. The first sequence began 21 s after the intravenous\ninjection of contrast. An additional upper abdomen diffusion-weighted sequence\nwas performed in order to identify distant metastases (to solid organs or lymph\nnodes).\nThe MRI scans were analyzed by two radiologists, one specializing in MRI of the\npelvis and the other specializing in MRI of the upper abdomen, who were working\nseparately and were blinded to the histological diagnosis, as well as to the\nfollow-up data. Both radiologists had vast prior experience (10 and 9 years,\nrespectively) in the analysis of pelvic MRI scan. For all of the adnexal masses,\neach radiologist calculated the O-RADS MRI score independently. Disagreements\nregarding the final classification were resolved by consensus.\nAdnexal masses were described with terms established in the literature and\nendorsed by the American College of Radiology ( 14 , 19 ) , involving morphological features on MRI and\nthe DCE standards necessary for applying the O-RADS MRI score.  Table 1  illustrates the categories and main\nfindings of the O-RADS MRI score.\nO-RADS MRI scoring system.\nSolid tissue is defined as a lesion component that enhances and\nconforms to one of these morphologies: papillary projection; mural\nnodule; irregular septation/wall; or other larger solid\nportions.\nMinimal enhancement of Rokitansky nodules in a lipid-containing\nlesion does not change the classification to O-RADS MRI 4.\nData were analyzed using the R Environment for Statistical Computing\nSoftware ( 22 ) . We calculated the sensitivity, specificity,\npositive predictive value, and negative predictive value for O-RADS MRI scores,\nusing ≥ 4 as the cutoff score for malignancy ( 17 , 18 ) . For statistical purposes,\nborderline ovarian tumors were classified as malignant.\n\nThe histological subtypes of benign and malignant adnexal masses are shown in  Table 2 . A final histopathological diagnosis\nwas made in 190 (66.20%) of the 287 masses evaluated in the present study. Because\nour hospital is a tertiary cancer center, the malignancy rate was high, 90 (47.37%)\nof those 190 masses being classified as malignant in the histopathological analysis.\nOf the remaining 97 masses, which were followed clinically, none showed signs of\nmalignant transformation, maintaining an O-RADS MRI score of 2 (almost certainly\nbenign) or 3 (low risk).  Figure 2  illustrates\nan adnexal mass in the right ovary, with an O-RADS MRI score of 3 (low risk), which\nwas resected surgically. In that case, the final histopathological diagnosis was\nbenign mucinous cystadenoma.\nFigure 2 A 43-year-old woman with chronic pelvic pain and a right adnexal mass\nidentified on ultrasound, with an indeterminate result based on the IOTA\nsimple rules. A: T2-weighted sagittal sequence showing a cystic adnexal\nmass with multiple septa (red arrows) centered in the right adnexal\nregion, near the bladder (asterisk). B: Contrast-enhanced axial\nfat-saturated T1-weighted sequence (acquisition at 30 s after contrast\nadministration) showing enhancement of some septa (yellow arrowheads),\nwith no solid portions. The final O-RADS MRI score was 3 (low risk). The\npatient underwent surgery (right oophorectomy), and the final\nhistological diagnosis was mucinous cystadenoma.\nA 43-year-old woman with chronic pelvic pain and a right adnexal mass\nidentified on ultrasound, with an indeterminate result based on the IOTA\nsimple rules. A: T2-weighted sagittal sequence showing a cystic adnexal\nmass with multiple septa (red arrows) centered in the right adnexal\nregion, near the bladder (asterisk). B: Contrast-enhanced axial\nfat-saturated T1-weighted sequence (acquisition at 30 s after contrast\nadministration) showing enhancement of some septa (yellow arrowheads),\nwith no solid portions. The final O-RADS MRI score was 3 (low risk). The\npatient underwent surgery (right oophorectomy), and the final\nhistological diagnosis was mucinous cystadenoma.\nCharacteristics and final diagnoses of adnexal masses (n = 287).\nTable 3  shows the final O-RADS MRI score for\nall adnexal masses, together with the sensitivity, specificity, positive predictive\nvalue, negative predictive value, positive likelihood ratio, and negative likelihood\nratio, with cutoff O-RADS MRI scores of 4 and 5 for malignancy. The O-RADS MRI score\nshowed a sensitivity and specificity of 91.11% and 94.92%, respectively, with an\noverall accuracy of 93.73%.\nDiagnostic performance of the O-RADS MRI score in adnexal masses (n =\n287). *\nTrue-positive results = 87; false-positive results = 10; true-negative\nresults = 188; false-negative results = 8.\nThe sensitivity, specificity, positive predictive value, and negative\npredictive value were computed for dichotomized scores: scores of 1, 2,\nand 3 (benign) vs. scores of 4 and 5 (malignant).\nTable 4  shows the adnexal masses for which\nthe O-RADS MRI score produced a false-positive or false-negative result, together\nwith the key imaging findings responsible for the diagnostic error. Among the eight\ncases of false-negative results, there were five malignant masses that did not\npresent an identifiable solid portion, which resulted in an O-RADS MRI score of 2 or\n3, and three malignant masses with a solid component that had a low-risk (type 1)\ntime-intensity curve, which resulted in an O-RADS MRI score of 3. Among the ten\ncases of false-positive results, there was a moderate-risk (type 2) time-intensity\ncurve, resulting in an O-RADS MRI score of 4, in all of the masses. None of the\nmasses presented a high-risk (type 3) time-intensity curve.\nDetails of adnexal masses erroneously categorized with the O-RADS MRI score\n(false positives and false negatives).\nFigure 3  illustrates an adnexal mass in the\nleft ovary, showing the visible enhancement pattern at 35 s after injection of the\ncontrast and the high-risk (type 3) time-intensity curve. For that mass, the O-RADS\nMRI score was 5 and the final histological diagnosis was high-grade serous\ncystadenocarcinoma with peritoneal carcinomatosis.  Figure 4  shows a solid-cystic mass, centered in the left adnexal region\nand extending to the upper abdomen, with lipid content and a large volume of\nenhancing solid tissue. The O-RADS MRI score for such masses is 4 ( 18 ) , and the final\nhistological diagnosis in that case was immature teratoma accompanied by gliomatosis\nperitonei.\nFigure 3 A 39 year-old woman with a family history of breast and ovarian cancer\nwho presented with pelvic pain and a left adnexal mass. A: Axial\nT2-weighted sequence showing a multilocular cystic mass with solid\nportions (yellow arrows) centered in the left adnexal region. B: Axial\nT2-weighted sequence showing the multilocular cystic mass and multiple\nperitoneal implants (red stars) near the uterus (blue asterisk). C:\nContrast-enhanced sagittal fat-saturated T1-weighted sequence (DCE\nstudy) showing visible enhancement of the solid component of the mass,\ngreater than that of the myometrium, at 35 s after contrast\nadministration. Note the region of interest over the uterus (blue\ncircle) and the other over the adnexal mass (red circle). D: Relative\nenhancement ratio curve showing that the initial increase in the\nenhancement of the mass was greater than was that of the uterus. The\nfinal O-RADS MRI score was 5 (high risk). The patient underwent surgery,\nand the final histological diagnosis was high-grade serous\ncystadenocarcinoma with peritoneal carcinomatosis.\nA 39 year-old woman with a family history of breast and ovarian cancer\nwho presented with pelvic pain and a left adnexal mass. A: Axial\nT2-weighted sequence showing a multilocular cystic mass with solid\nportions (yellow arrows) centered in the left adnexal region. B: Axial\nT2-weighted sequence showing the multilocular cystic mass and multiple\nperitoneal implants (red stars) near the uterus (blue asterisk). C:\nContrast-enhanced sagittal fat-saturated T1-weighted sequence (DCE\nstudy) showing visible enhancement of the solid component of the mass,\ngreater than that of the myometrium, at 35 s after contrast\nadministration. Note the region of interest over the uterus (blue\ncircle) and the other over the adnexal mass (red circle). D: Relative\nenhancement ratio curve showing that the initial increase in the\nenhancement of the mass was greater than was that of the uterus. The\nfinal O-RADS MRI score was 5 (high risk). The patient underwent surgery,\nand the final histological diagnosis was high-grade serous\ncystadenocarcinoma with peritoneal carcinomatosis.\nFigure 4 A 28-year-old woman with a left adnexal mass, extending to the upper\nabdomen, which had been considered indeterminate on ultrasound with the\napplication of the IOTA simple rules. A: Axial T2-weighted sequence\nshowing a solid-cystic mass (red arrows) centered in the left adnexal\nregion. Note the ascites (asterisk). B,C: In-phase and out-of-phase\nT1-weighted sequences showing multiple foci of fat (signal drop in the\nout-of-phase sequence; red arrows), consistent with a germ cell tumor.\nD: Contrast-enhanced sagittal fat-saturated T1-weighted sequence\n(acquisition at 35 s after contrast administration) showing enhancement\nof the solid portions of the mass (red arrowheads) less than that of the\nmyometrium (green arrows). Note the ascites (white star) and the\nlocation of the bladder (white circle). The final O-RADS MRI score was 4\n(intermediate risk). The patient underwent surgery, and the final\nhistological diagnosis was immature teratoma accompanied by gliomatosis\nperitonei.\nA 28-year-old woman with a left adnexal mass, extending to the upper\nabdomen, which had been considered indeterminate on ultrasound with the\napplication of the IOTA simple rules. A: Axial T2-weighted sequence\nshowing a solid-cystic mass (red arrows) centered in the left adnexal\nregion. Note the ascites (asterisk). B,C: In-phase and out-of-phase\nT1-weighted sequences showing multiple foci of fat (signal drop in the\nout-of-phase sequence; red arrows), consistent with a germ cell tumor.\nD: Contrast-enhanced sagittal fat-saturated T1-weighted sequence\n(acquisition at 35 s after contrast administration) showing enhancement\nof the solid portions of the mass (red arrowheads) less than that of the\nmyometrium (green arrows). Note the ascites (white star) and the\nlocation of the bladder (white circle). The final O-RADS MRI score was 4\n(intermediate risk). The patient underwent surgery, and the final\nhistological diagnosis was immature teratoma accompanied by gliomatosis\nperitonei.\n\nThe sensitivity, specificity, and overall accuracy of the O-RADS MRI score in the\npresent study were similar to those reported for the original score ( 17 ) , which further supports\nits use in the assessment of adnexal masses, especially those considered\nindeterminate on ultrasound. In the O-RADS MRI protocol, it is necessary to include\nsequences aimed at evaluating the morphology of the adnexal mass—at least two\nT2-weighted multiplanar sequences (axial and sagittal or coronal) and T1-weighted\nsequences, with and without fat saturation, in order to stratify fat and blood\ncomponents—and advanced sequences—diffusion-weighted sequences with\n b  values of 800-1200 s/mm 2  (enough\n b  to suppress the T2 shine-through effect, thus ensuring that\nthe urine in the bladder is black) and a DCE study, with a time resolution ≤\n15 s and a total time after gadolinium injection of 180 s. If DCE is unavailable\n(because of limitations of the magnet or software), the contrast uptake can be\nanalyzed visually (at 30-40 s after gadolinium injection). In addition, the use of\ngadolinium can be foregone if no suspicious adnexal lesion is identified in the\nanalysis of the conventional (T1- and T2-weighted) sequences, such as when only\nfollicles or the corpus luteum are identified in a premenopausal patient.\nThe contrast uptake (DCE) study is the cornerstone of the O-RADS MRI score, defining\nthe cutoff scores of 4 and 5. A moderate or marked increase in the signal intensity\nof an ovarian mass, in relation to that of the uterus, after gadolinium injection is\nassociated with borderline and malignant tumors, correlating directly with the\nangiogenic status of a tumor ( 23 - 25 ) . In the initial study of the ADNEX MR SCORING\nsystem ( 14 ) ,\nthe DCE study images were obtained sequentially at intervals of 2.4 s, starting from\n10 s after injection of the contrast, over a total of 320 s, with consequent\npost-processing on a workstation. That technical requirement was very rigid and\ncomplex, which could limit its use in clinical practice, a difficulty acknowledged\nby the authors ( 15 ) . The\nO-RADS MRI score allows the use of lower temporal resolution in the DCE study, with\nintervals of ≤ 15 s and a total acquisition time of 180 s, as well as\nincluding the option of performing a comparative visual analysis between the pattern\nof enhancement of the adnexal mass and that of the myometrium (at 30-40 s after\ngadolinium injection) when a DCE study is not available ( 18 ) . Those changes will\nallow the dissemination of the O-RADS MRI score to a greater number of MRI\ndiagnostic centers, even those using low-field scanners, which is still a reality in\nlow- and middle-income countries ( 26 ) .\nAnother update was the classification of adnexal masses with lipid content and a\nlarge volume of enhancing solid tissue as deserving of an O-RADS MRI score of\n4 ( 18 ) . That\nis important because some malignant tumors with a fat component, such as immature\nteratomas, can mimic benign lesions and need to be carefully\nevaluated ( 27 ) . However, minimal enhancement of Rokitansky nodules in a\nlesion containing lipid does not change the classification to an O-RADS MRI score of\n4 ( 18 ) .\nTherefore, according to the O-RADS MRI scoring system, not every adnexal mass with\nfat content is benign, especially in women under 20 years of age, with or without\nchanges in serum biomarkers, lactic dehydrogenase, and\nalpha-fetoprotein ( 28 , 29 ) .\nCertain diagnostic challenges persist, especially in cases of borderline tumors or\ninvasive malignant tumors with type 1 time-intensity curves or without clearly solid\nportions, which were the main causes of the false-negative O-RADS MRI score results\nin the present study. The use of new diagnostic parameters and imaging concepts,\nespecially radiogenomics studies ( 30 )  and tailored imaging protocols for borderline\nmalignancy ( 31 ) , could facilitate the stratification of such tumors.\nOur study has some limitations. First, it was conducted at a tertiary cancer center,\nwhich increased the positive predictive value for malignancy in our sample. In\naddition, MRI reporting was performed by experienced examiners, whereas it is\nrecommended that the reporting be performed by less experienced examiners or\ngeneralist radiologists. Furthermore, we did not assess the accuracy of the use of a\nsingle analysis of enhancement at 30-40 s after gadolinium injection in determining\nO-RADS MRI scores of 4 and 5, which could have altered our findings. Other authors\nhave even evaluated the use of unenhanced images to construct the O-RADS MRI score,\nespecially when clinical conditions, such as nephropathy or severe\nallergy ( 32 ) , preclude the use of contrast.\nIn summary, our data support the use of the O-RADS MRI score to assess adnexal\nmasses, especially those considered indeterminate on ultrasound. The latest updates\nto the O-RADS MRI score facilitate its interpretation and will allow its use to\nbecome more widespread, with no loss of diagnostic accuracy.","source_license":"CC-BY-4.0","license_restricted":false}