Likelihood Ratio of Sonohysterographic Findings for Discriminating Endometrial Polyps From Submucosal Fibroids
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1 ORIGINAL RESEARCH Likelihood Ratio of Sonohysterographic Findings for Discriminating Endometrial Polyps From Submucosal Fibroids Mousumi Bhaduri, MBBS, DMRD, DNB, DABR, George Tomlinson, PhD, Phyllis Glanc, MD, FRCPC Received November 7, 2012, from the Department of Medical Imaging, Schulich School of Medicine and Dentistry, University of Western Ontario, London Health Sciences Center Victoria Hospital, London, Ontario, Canada (M.B.); Departments of Medicine (G.T.), Radiology (P.G.), and Obstetrics and Gynecology (P.G.), University of Toronto, Toronto, Ontario, Canada; and Obstetric Ultrasound Unit, Department of Medical Imaging, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada (P.G.). Revision requested December 28, Revised manuscript accepted for publication May 28, Address correspondence to Mousumi Bhaduri, MBBS, DMRD, DNB, DABR, Department of Medical Imaging, Schulich School of Medicine and Dentistry, University of Western Ontario, London Health Sciences Center Victoria Hospital, 800 Commissioners Rd E, Room D1-106, London, ON N6A 5W9, Canada. Abbreviations CI, confidence interval; LR, likelihood ratio doi: /ultra Objectives The purpose of this study was to determine which combination of sonohysterographic features has the highest likelihood ratios (LRs) in discriminating polyps from submucosal fibroids. Methods This retrospective study included 200 consecutive patients who underwent both sonohysterography and a procedure resulting in a positive pathologic diagnosis. A reader, masked to the imaging and pathologic findings, independently reviewed the 200 sonograms and recorded the findings using a standardized checklist for sonographic features on sonohysterography. The features assessed included angle, echogenicity, endometrial-myometrial interface, and vascular pattern, among others. The reader chose one final diagnosis from the list of possibilities, which included normal, hyperplasia, polyp, submucosal fibroid, cancer, adhesions, and clots. Sonographic observations were then compared to pathologic findings. Results The LR of 13.4 was achieved for polyps when there was a combination of an intact endometrial-myometrial interface, a single vessel, an acute angle, and homogeneous echogenicity. The highest LR of 27.8 was achieved for submucosal fibroids when the combination of sonographic features included an absent endometrial-myometrial interface, an arborized/multiple vascular pattern, an obtuse angle, and heterogeneous echogenicity. Conclusions A combination of sonographic findings may provide high LRs for discriminating endometrial polyps from submucosal fibroids. Key Words fibroids; gynecologic ultrasound; likelihood ratio; polyps; sonohysterographic features The most common endometrial abnormalities in women of any age group are fibroids and polyps. 1 Fibroids are extremely common and are found in 70% to 80% of women by 50 years of age. 2 The prevalence of endometrial polyps varies between 6% and 32%, depending on the definition of a polyp, the diagnostic method used, and the population studied. 3 The distinction between these two entities is important, as a submucosal or an intracavitary fibroid is a benign condition, which is typically treated conservatively. Patients with intractable symptoms may undergo uterine artery embolization or surgical resection to obtain symptomatic relief. Endometrial polyps, although also typically benign, are surgically resected, as imaging is unable to distinguish those with benign versus those with malignant histologic characteristics. Thus it is important for imaging to accurately discriminate between these two entities by the American Institute of Ultrasound in Medicine J Ultrasound Med 2014; 33:
2 Multiple studies have described various sonohysterographic features associated with endometrial polyps and submucosal fibroids. The described features for polyps include a pedicle artery sign, 4 6 a uniform echo texture 4 that is isoechoic to the endometrium, 7 an acute angle to the endometrium, an intact endometrial-myometrial interface, 1,8 and smooth margins. For submucosal fibroids, the described features include a broad-based 5 variably hypoechoic mass with an intracavitary component, 4 shadowing, 9 an overlying echogenic endometrium, 1,4 and an arborized vascular pattern. 5 We designed our study to determine which combination of sonographic features has the highest likelihood ratios (LRs) in identifying and distinguishing polyps from submucosal fibroids. Materials and Methods Institutional Research Ethics Board approval was obtained. This study consisted of a retrospective review of 200 consecutive patients who had undergone both sonohysterography and a pathologic diagnosis. The histologic diagnosis, demographic data, and additional information such as menstrual status were obtained. Each case was reviewed with the use of a standardized checklist of features and diagnoses (Table 1). 10 A single reviewer was masked to the original interpretation, the clinical history, and the pathologic diagnosis. The specific diagnoses that could be made were as follows (1) normal, (2) endometrial polyp, (3) endometrial hyperplasia, (4) endometrial cancer, (5) submucosal fibroid, (6) adenomyosis, (7) adhesions, and (8) blood clots. The total population of 200 was then segregated into 3 groups: (1) polyps, (2) submucosal fibroids, and (3) others, including normal, endometrial hyperplasia, endometrial cancer, adenomyosis, adhesions, and blood clots. Each finding was assessed independently from the other findings without consideration of the reader s overall impression. The final diagnosis was determined by reviewing the original report and the final pathologic report. For each of the 2 most common diagnoses (endometrial polyp and submucosal fibroid), the LR and its 95% confidence interval (CI) were computed for each of the 14 possible combinations of 4 common findings that could be evaluated in both diagnoses: (1) whether the lesion had a homogeneous or heterogeneous echo pattern (Figure 1); (2) intactness of the endometrial-myometrial interface (Figure 1); (3) whether the angle of the lesion was acute or obtuse with respect to the underlying endometrial layer (Figure 2); and (4) whether the vascular pattern was a single pedicle, multiple pedicles, or other (which included an absent or indeterminate pattern; Figure 3). For the diagnosis of a polyp, for example, the LR for a specified combination of the 4 findings is the percentage of polyps with that combination divided by the percentage of nonpolyps with that combination. 11 An LR greater than 1 means that the combination of findings increases the chance that a case has a polyp, whereas a value less than 1 indicates a decreased chance that the case has a polyp. 12,13 All analyses were performed in R version software. 14 Results Of the 200 patients identified in the retrospective consecutive analysis, 116 (58%) were premenopausal, 66 (33%) were postmenopausal, and 18 (9%) were perimenopausal. Table 1. Standardized Checklist of Features and Diagnoses for Focal Lesions Size: maximum dimension (mm) Location: n submucous n intramural n intracavitary ( n <50% n >50% n entirely) Configuration: n sessile n pedunculated n linear Borders: n well defined n poorly defined Angle to endometrium: n acute n obtuse Margins: n smooth n irregular n lobulated n frondlike Echogenicity of lesion: n homogeneous n heterogeneous Echogenicity with respect to endometrium: n isoechoic n hyperechoic n hypoechoic Echogenicity with respect to myometrium: n isoechoic n hyperechoic n hypoechoic Cystic changes: n single n multiple n none Feeding vessels: n absent n multiple n single Edge shadows: n absent n present Refractive shadows: n absent n present Overlying endometrium: n absent n present Endometrial-myometrial interface: n absent n intact 150 J Ultrasound Med 2014; 33:
3 Figure 1. Echogenicity and endometrial-myometrial interface. Left, Homogeneously echogenic polyp with an intact underlying endometrial-myometrial interface (arrows). Right, Heterogeneous submucosal fibroid with no underlying endometrial-myometrial interface (arrows). The mean age was 50 years (range, years). The diagnostic procedures leading to histologic diagnoses were dilation and curettage (30%), hysteroscopy (66.5%), unknown (2.5%), and myomectomy (1%). There were a total of 263 findings on sonohysterography, which included the following: 130 polyps (49.4%), 25 submucosal fibroids (9.5%), 43 normal (16.3%), 24 adenomyosis (9.1%), 20 endometrial hyperplasia (7.6%), 14 adhesions (4.9%), 4 blood clots (1.5%), and 3 endometrial cancers (1.1%). Of the 130 polyps on sonohysterography, 125 were pathologically proven polyps, and their sonographic features were assessed. Of the 25 submucosal fibroids on sonohysterography, 10 were pathologically proven. For the 125 cases of pathologically proven polyps, the sonographic features were tabulated. An acute angle was present in 123 (98.4%); a homogeneous echo pattern was seen in 121 (96.8%); echogenicity with respect to the myometrium was seen in 124 (99.2%); a smooth margin was seen in 123 (98.4%); a single feeding vessel was present in 53 (42.4%), an absent feeding vessel was seen in 52 (41.6%); an intact interface was seen in 124 (99.2%); and cysts were absent in 115 (92%). For the 25 cases of submucosal fibroids, the sonographic features were tabulated. An obtuse angle was present in 10 (41.7%); the echo pattern was heterogeneous in 19 (76%); an arborizing vascular pattern was present in 15 (60%); the endometrial-myometrial interface was absent in 24 (96%); shadowing was present in 17 (68%); an overlying endometrium was defined in 25 (100%); and 24 (96%) were sessile. The highest LR of 13.4 was achieved for polyps when there was a combination of an intact endometrialmyometrial interface, a single vessel, an acute angle, and homogeneous echogenicity. The highest LR of 27.8 was Figure 2. Angles of lesions with respect to the underlying endometrial layer. Left, Acute angle in a polyp (arrows). Right, Obtuse angle in a submucosal fibroid (arrow). J Ultrasound Med 2014; 33:
4 Figure 3. Vascular patterns of lesions. Left, Single pedicle in a polyp (arrow). Right, Arborized pattern in a submucosal fibroid. achieved for submucosal fibroids when the combination of sonographic features was an absent endometrialmyometrial interface, an arborized/multiple vascular pattern, an obtuse angle, and heterogeneous echogenicity. There were other combinations that also achieved high LRs in both categories, which are detailed in Tables 2 (polyps) and 3 (submucosal fibroids). The third group of others was small, and individually, these entities had a small sample size (<10) and thus were excluded from further analysis. Discussion The LR ratio does not change with disease prevalence and can be used for tests with multiple categories. It provides an easily comprehensible measure of computing posttest probability of a disease, making it a powerful clinical tool. 15 By using a combination of sonographic features, a high LR may be achieved for a given diagnosis, thus improving the likelihood of a positive test result in the presence of the characteristic(s). This approach can be used to provide a sonographic feature based analysis, which may provide improved accuracy over a gestalt approach. Table 2. Performance of Combinations of Features for the Diagnosis of Polyps LR 95% CI Interface Vascularity Angle Echogenicity Intact Single Acute Homogeneous Intact Other Acute Homogeneous Intact Multiple Acute Homogeneous Intact Other Other Other The highest LR of 13.4 was achieved for polyps when there was a combination of an intact endometrialmyometrial interface, a single vessel, an acute angle, and homogeneous echogenicity. The highest LR of 27.8 was achieved for submucosal fibroids when the combination of sonographic features included an absent endometrialmyometrial interface, an arborized/multiple vascular pattern, an obtuse angle, and heterogeneous echogenicity. The additional features, although individually evaluated, were not incorporated into LRs, as they could not be compared in both conditions. Confidence intervals for some of the LRs in Tables 2 and 3 are large because there were small numbers with those specific combinations of features. There are many articles in the literature describing the features of various endometrial and subendometrial pathologic entities on sonohysterography. 1,8,16,17 This article provides a unique look at which combined sonographic features provide the greatest LR in a population with intracavitary masses. In the population we evaluated, although there was a spectrum of intracavitary masses, only polyps and submucosal fibroids occurred with adequate frequency for further evaluation. Table 3. Performance of Combinations of Features for the Diagnosis of Submucosal Fibroids LR 95% CI Interface Vascularity Angle Echogenicity Absent Multiple Obtuse Heterogeneous Absent Other Obtuse Heterogeneous Absent Multiple Acute Heterogeneous Absent Other Acute Heterogeneous Intact Other Other Other 152 J Ultrasound Med 2014; 33:
5 An intact regular endometrial-myometrial interface has been described in the appearance of a typical polyp. 1,8 In our study, 98.5% had an intact interface. It was absent or difficult to assess in the 3 cases (1.5%) that were diagnosed as endometrial cancer. Fistonic et al 18 assessed the various features of malignancy and found 100% sensitivity for an irregular myometrial-endometrial interface in predicting endometrial carcinoma. Using the interface as one of the criteria, none of the cases with a benign diagnosis were misdiagnosed in this study. Timmerman et al 6 assessed the value of the pedicle artery sign for detecting focal intracavitary disease with a positive predictive value of 81.3%. In our study, a vascular pedicle was seen in 42.4% of the polyps, multiple vessels in 8%, and vessels were not shown in the remainder. We speculate that because this study was retrospective, the original examiner may not have tried to show or document the vascular pattern in many of the cases, perhaps thinking that the diagnosis was obvious. Up to 60% of the submucosal fibroids in our study had an arborizing vascular pattern, and none showed a single feeding vessel. Jorizzo et al 19 found that the most important features for distinguishing a polyp from a submucosal fibroid were the echo texture and presence of an overlying endometrium, as they differentiated endometrial from subendometrial pathologic entities. All of the submucosal fibroids in our study had an identifiable overlying endo - metrium. Another study by Jorizzo et al 17 described the echo texture of a submucosal fibroid as hypoechoic 17 ; however, in our study, 76% were heterogeneous, which was in agreement with a study by Laifer-Narin et al, 7 who found a heterogeneous echo texture of a submucosal fibroid to be a statistically significant feature for the diagnosis. The study by Laifer-Narin et al 7 also found uniform increased echogenicity to be a statistically significant feature for the diagnosis of polyp. In our study, 99.2% of the polyps were isoechoic to the endometrium with uniform increased echogenicity compared to the underlying myometrium. Caoili et al 9 saw a strong association (with specificity of 90%) of refractory shadowing with the diagnosis of a fibroid within an intrauterine mass. In our study, 85.7% of the submucosal fibroids had refractive and edge shadowing. Our study had certain limitations. The cases were defined as those that had both sonohysterogram and a pathologic report, thus skewing the population to those who were either symptomatic or had a concerning appearance that would lead to a definitive procedure. This factor likely accounts for the high proportion of endometrial polyps on the final pathologic examinations (125) versus only 10 submucosal fibroids. All 25 sonographically diagnosed fibroids were included in the study if they achieved final diagnostic consensus between the reader and the original diagnosis. Although our study population had the spectrum of endometrial and subendometrial abnormalities, the sample sizes of individual pathologic entities other than polyps and submucosal fibroids were too small for further analysis. In conclusion, using specific combinations of sonographic characteristics can increase the likelihood of a positive test result for discriminating endometrial polyps from submucosal fibroids. References 1. Davis PC, O Neill MJ, Yoder IC, Lee SI, Mueller PR. Sonohysterographic findings of endometrial and subendometrial conditions. Radiographics 2002; 22: Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril 2007; 87: Dreisler E, Stampe Sorensen S, Ibsen PH, Lose G. Prevalence of endometrial polyps and abnormal uterine bleeding in a Danish population aged years. Ultrasound Obstet Gynecol 2009; 33: Berridge DL, Winter TC. Saline infusion sonohysterography: technique, indications, and imaging findings. J Ultrasound Med 2004; 23: Bree RL, Bowerman RA, Bohm-Velez M, et al. US evaluation of the uterus in patients with postmenopausal bleeding: a positive effect on diagnostic decision making. Radiology 2000; 216: Timmerman D, Verguts J, Konstantinovic ML, et al. The pedicle artery sign based on sonography with color Doppler imaging can replace secondstage tests in women with abnormal vaginal bleeding. Ultrasound Obstet Gynecol 2003; 22: Laifer-Narin SL, Ragavendra N, Lu DS, Sayre J, Perrella RR, Grant EG. Transvaginal saline hysterosonography: characteristics distinguishing malignant and various benign conditions. AJR Am J Roentgenol 1999; 172: Nalaboff KM, Pellerito JS, Ben-Levi E. Imaging the endometrium: disease and normal variants. Radiographics 2001; 21: Caoili EM, Hertzberg BS, Kliewer MA, DeLong D, Bowie JD. Refractory shadowing from pelvic masses on sonography: a useful diagnostic sign for uterine leiomyomas. AJR Am J Roentgenol 2000; 174: Bhaduri M, Khalifa M, Tomlinson G, Glanc P. Sonohysterography: the utility of diagnostic criteria sets. AJR Am J Roentgenol 2012; 198:W83 W Black WC, Armstrong P. Communicating the significance of radiologic test results: the likelihood ratio. AJR Am J Roentgenol 1986; 147: Stengel D, Bauwens K, Sehouli J, Ekkernkamp A, Porzsolt F. A likelihood ratio approach to meta-analysis of diagnostic studies. 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6 14. R Foundation for Statistical Computing. R: a language and environment for statistical computing. R Foundation for Statistical Computing website; Gallagher EJ. Clinical utility of likelihood ratios. Ann Emerg Med 1998; 31: Parsons A, Hill A, Spicer D. Sonohysterographic imaging of the endometrial cavity. Front Biosci 1996; 1:f1 f Jorizzo JR, Riccio GJ, Chen MY, Carr JJ. Sonohysterography: the next step in the evaluation of the abnormal endometrium. Radiographics1999; 19(special issue):s117 S Fistonic I, Hodek B, Klaric P, Jokanovic L, Grubisic G, Ivicevic-Bakulic T. Transvaginal sonographic assessment of premalignant and malignant changes in the endometrium in postmenopausal bleeding. J Clin Ultrasound 1997; 25: Jorizzo JR, Chen MY, Riccio GJ. Endometrial polyps: sonohysterographic evaluation. AJR Am J Roentgenol 2001; 176: J Ultrasound Med 2014; 33:
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