Research. The hysteroscopic removal of asymptomatic

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1 Research GENERAL GYNECOLOGY How often are endometrial polyps malignant in asymptomatic postmenopausal women? A multicenter study Enrico Ferrazzi, MD; Errico Zupi, MD; Francesco P. Leone, MD; Luca Savelli, MD; Umberto Omodei, MD; Massimo Moscarini, MD; Maurizio Barbieri, MD; Giuseppe Cammareri, MD; Giampiero Capobianco, MD; Ettore Cicinelli, MD; Maria E. Coccia, MD; Gloria Donarini, MD; Simona Fiore, MD; Paolo Litta, MD; Mario Sideri, MD; Eugenio Solima, MD; Donata Spazzini, MD; Antonia C. Testa, MD; Massimo Vignali, MD OBJECTIVE: The objective of the study was to evaluate the prevalence of cancer and premalignant lesions in polyps on atrophic endometrium in asymptomatic postmenopausal women to compare these findings with a similar cohort of patients with abnormal uterine bleeding. STUDY DESIGN: One thousand one hundred fifty-two asymptomatic and 770 consecutive postmenopausal women with abnormal uterine bleeding were included in a retrospective multicenter study. Recruited patients underwent hysteroscopic polypectomy based on a sonohysterographic or hysteroscopic diagnosis. The pathologic report was the main outcome measure. RESULTS: One single case of stage 1 grade 1 endometrial carcinoma on a polyp with a mean diameter of 40 mm (0.1%) was observed in asymptomatic women. This prevalence was 10 times lower than in symptomatic patients (P.0001). The prevalence of atypical hyperplastic polyps was 1.2% in asymptomatic women (2.2% in symptomatic patients; P.005). At multivariate analysis, polyps diameter was the only variable significantly associated to an abnormal histology (cancer, polypoid cancer, and atypical hyperplasia) in asymptomatic women (odds ratio for polyps with mean diameter 18 mm, 6.9; confidence interval, ). CONCLUSION: Follow-up and/or treatment of endometrial polyps incidentally diagnosed in asymptomatic postmenopausal patients could be safely restricted to few selected cases based on polyp diameter. Key words: asymptomatic endometrial polyps, endometrial cancer, hysteroscopy, polypectomy Cite this article as: Ferrazzi E, Zupi E, Leone FP, et al. How often are endometrial polyps malignant in asymptomatic postmenopausal women? A multicenter study. Am J Obstet Gynecol 2009;200:235.e1-235.e6. From the Department of Obstetrics and Gynecology (Drs Ferrazzi, Leone, and Fiore), DSC L. Sacco, University of Milan, Milan; the Department of Surgery, Obstetrics, and Gynecology Unit (Dr Zupi), University of Rome Tor Vergata, Rome; the Department of Obstetrics and Gynecology (Dr Savelli), University of Bologna, Bologna; the Department of Obstetrics and Gynecology (Drs Omodei and Donarini), University of Brescia, Brescia; the Department of Obsterics and Gynecology (Dr Moscarini), University of Rome Sapienza, Roma; the Department of Obstetrics, Gynecology (Dr Barbieri), and Neonatology, Policlinico- Mangiagalli-Regina Elena Foundation, Milan; the Department of Obstetrics and Gynecology (Dr Cammareri), Ospedale V. Buzzi, Milan; Department of Pharmacology, Gynecology, and Obstetrics (Dr Capobianco), University of Sassari, Sassari; the Department of Obstetrics and Gynecology (Dr Cicinelli), University of Bari, Bari; Department of Gynecology, Perinatology, and Human Reproduction (Dr Coccia), University of Florence, Florence; the Department of Gynecological Science and Human Reproduction (Dr Litta), University of Padua, Padua; Division of Gynecology (Dr Sideri), European Institute of Oncology, Milan; the Department of Gynecologic Oncology (Dr Solima), Istituto Nazionale Tumori, Milan; the Department of Obstetrics and Gynecology (Dr Spazzini), Ospedali Riuniti di Bergamo, Bergamo; the Gynecologic Oncology Unit (Dr Testa), Catholic University of the Sacred Heart, Rome; and the Department of Obstetrics and Gynecology (Dr Vignali), Macedonio Melloni Hospital, University of Milan, Milan, Italy. Received April 24, 2008; revised July 29, 2008; accepted Sept. 30, Reprints not available from the authors /$ Published by Mosby, Inc. doi: /j.ajog The hysteroscopic removal of asymptomatic polyps in postmenopause has slipped into clinical practice either as a prudent removal of a lesion whose malignant potential is low but not well established 1,2 or as an active consequence of the assumption that this is a cost-effective secondary prevention of endometrial malignancy. 3,4 In some countries and in Italy, there is a sort of natural endometrial screening in asymptomatic patients because of the wide use of ultrasound units in outpatient clinics. This see-and-treat management is questionable because it is based on experts opinions and few published data. 5 Nevertheless, this is determining additional costs and medical and psychological side effects with no sound evidence of benefits for patients. As far as the objective of an accurate diagnosis is concerned, sonohysterography and office hysteroscopy are by far the most credited procedures to apply when a polyp is suspected at transvaginal ultra- MARCH 2009 American Journal of Obstetrics & Gynecology 235.e1

2 Research General Gynecology sound examination of the uterus. Both techniques have limitations, but their standard performance allows defining the surrounding endometrium, the macroscopic aspect of the polyp, 6,7 and even its vascular stalk. 8 As far as the malignant potential of asymptomatic polyps is concerning caregivers, there appears to be a contradiction between the high prevalence of this benign lesion in asymptomatic women reported by pathological series, 9-11 which set this figure up to 20% and suggested management by clinical series that recommend an universal removal of polyps in those women in which they are incidentally observed. 3,4,12,13 Unfortunately, in most quoted clinical cohorts pre- and postmenopausal women are mixed together, occasional findings in asymptomatic women are analyzed together with symptomatic patients as well as women at risk for endometrial lesions because of hormonal therapies such as oestrogens or tamoxifen. 1,12,13 Furthermore, the actual presence or absence of the polyp itself could be biased by different removal procedure. 14 To make things more confused, the pathologic diagnosis may vary. According to Peterson and Novak 15 and Coeman et al, 16 the stalk and the surrounding endometrium must be free of cancer, which excludes polyps invaded by endometrial cancer but also excludes cancer spread from the polyp into atrophic endometrium. This cancer extension can be included in the diagnosis of polyps according to Farrel et al. 17 These pathological aspects are important for the matching with both sonographic and hysteroscopic findings. The aspect of the surrounding endometrium, which could be classified as thickened or atrophic, is able to differentiate 2 classes of patients: those with thickened endometrium and polyps, possibly associated at least with hyperplasia (up to 10% of cases 10,14 ), and those with atrophic endometrium, which represent the largest amount of cases found in postmenopausal asymptomatic patients The aim of this retrospective multicenter study was to assess the prevalence of cancer and premalignant lesions in polyps on atrophic endometrium in a large, well-defined subset of asymptomatic postmenopausal patients and to compare its relative prevalence in a similar cohort of symptomatic patients with abnormal uterine bleeding. MATERIALS AND METHODS This retrospective multicenter study included 13 university and tertiary care centres as part of a survey carried out by the task force on abnormal uterine bleeding of Associazione Ginecologi Universitari Italiani (AGUI). Clinical records were obtained from each institute by the principal local investigator who reviewed cases in each center according to local ethical and institutional regulations. Clinical records of office operative hysteroscopies and resectoscopic procedures for endometrial polyps were searched over a retrospective period of 30 months. Inclusion criteria were limited to women in postmenopause for more than 6 months. Abnormal uterine bleeding, defined as any bleeding, including spotting in the last 6 months, was searched in the main diagnosis and the clinical history of the patient to stratify patients in the 2 groups: asymptomatic women and patients with abnormal uterine bleeding. The final restrictive criteria for inclusion were a sonohysterography or a hysteroscopic diagnosis of polyp on atrophic endometrium: endometrial bilayer thickness of 4 mm or less at sonohysterography or atrophy visually diagnosed at hysteroscopy. These 2 diagnostic procedures were considered comparable for the purpose of this study. Sixty-six percent of polyps were diagnosed by sonohysterography. Patients ever having been on tamoxifen were excluded. One thousand nine hundred twentytwo clinical records of patients treated for endometrial polyps met the inclusion criteria and were recruited for this retrospective study from January 2005 to December They represent a consecutive series of cases diagnosed in the network centers. The median number of cases contributed by these centres was 115 (interquartile range [IR], ) over a period of 30 months. The proportion of asymptomatic vs symptomatic polyps varied in these centers between 7.11 and 0.20, the median being 1.56 (IR, ). The mean diameter of the polyp was obtained by direct ultrasound measurements. Baseline patients characteristics such as age, age at menopause, years after menopause, body mass index, history of hypertension, and diabetes were recorded accessing patients clinical history. In those centers in which the archiving system could potentially cause misclassifications, clinical records were also searched for abdominal hysterectomies with the final diagnosis of endometrial carcinoma. This search was conducted to avoid missing cases of women with coexisting diseases who were treated directly by abdominal surgery without resorting to hysteroscopic polypectomy. The main outcome was a detailed pathologic report. In case of multiple polyps, the one with the worst pathologic report was considered for this study. A benign polyp was diagnosed when the resected lesion proved to be benign or hyperplastic glands and fibrous stroma, supported by a bundle or leash of large vessels. 20 According to Farrel et al, 17 a malignant polyp was defined as a malignancy occurring within an elevation above the endometrial surface, in which there was evidence of a benign polyp. According to these definitions, polypoid carcinoma should have been excluded from the present analysis. However, because pathologic diagnosis of polypoid carcinoma occurred in both asymptomatic and symptomatic patients in whom preresectoscopic diagnosis met the required criteria of polyp on atrophic endometrium, these cases were included. Procedures All polyps were removed either by resectoscopic polypectomy under general anesthesia or operative office hysteroscopy. The main outcome measure was the final pathologic report obtained and checked for all cases included. An abnormal outcome was defined by the presence of endometrial cancer or atypical hyperplasia. Atrophic fibroglandular polyps and typical hyperplastic endometrial lining were considered benign outcome. 235.e2 American Journal of Obstetrics & Gynecology MARCH 2009

3 General Gynecology Research Statistics Descriptive, parametric, and nonparametric statistics were applied when appropriate to compare demographic and clinical findings within and between the 2 groups. The diameter of polyps was always treated by nonparametric variables to provide a better description for the few abnormal cases. Both univariate and multivariate logistic regression were performed to analyze all variables, and any possible independent variable significantly associated with an abnormal outcome. For possible clinical use, analyses were stratified by being symptomatic or not to eliminate the major independent factor. Age, year of menopause, and polyps diameter were also analyzed as categorized variables assuming the upper quartile value of normal cases in both series as a proper cutoff. MS Access 2000 (Microsoft Corp, Redmond, WA) was used for data entry and data management. Univariable and multivariable logistic regression were performed using STATA7 (StataCorp, College Station, TX) TABLE 1 Final histological diagnosis of polyps removed by operative hysteroscopy in asymptomatic women and symptomatic patients Asymptomatic Symptomatic P value Total, n Benign lesions 1134 (98.4%) 724 (94%) ns Atrophic glandulocystic polyps 1092 (94.7%) 663 (86.1%) ns Typical hyperplastic polyps 42 (3.6%) 61 (7.9%).05 Precancerous cancer lesions 18 (1.6%) 46 (6.0%).001 Atypical hyperplastic polyps 14 (1.2%) 17 (2.2%).05 Cancer on glandulocystic polyp 1 (0.1%) 8 (1.0%).001 Polypoid cancers 3 (0.3%) 21 (2.7%).001 Number of cases and relative percentage rounded to the first digit in parentheses. The univariate analysis between asymptomatic women with normal and abnormal histological diagnosis is reported in Table 2. The median diameter of polyps was significantly larger in cancer and premalignant lesions. Tables 3 and 4 show the descriptive statistics of baseline data of cases with abnormal histological findings in asymptomatic and symptomatic cases. Overall, only 6 cases of histological abnormal polyps in asymptomatic women (0.5%) showed a diameter less than 18 mm, which is the upper quartile range of polyps with normal histology The univariate analysis between symptomatic patients with normal and abnormal outcome is reported in Table 5. Pol- RESULTS The histological results of the 2 groups are reported and compared in Table 1. Only 1 case of endometrioid grade 2 adenocarcinoma on a polyp with a mean diameter of 40 mm was found in an asymptomatic patient. Eight cases of cancer on polyps were found in symptomatic patients, 2 of which proved type 2 endometrial carcinoma. Twenty-four cases with polypoid cancer were included, only 3 in asymptomatic patients. Eleven were diagnosed as polyps by hysteroscopy and 13 by sonohysterography. All 3 polypoid cancer cases in asymptomatic women were of the endometrioid type, 2 grade 1 and 1 grade 2 adenocarcinoma. On the other hand, 8 of the 21 cases in symptomatic patients were type 2 endometrial carcinoma. Polyps diameter in these 8 cases varied from 6 to 32 mm. Cancer on granulocytic polyps and polypoid carcinoma were 10 times more frequent in symptomatic than asymptomatic patients. TABLE 2 Univariate analysis for demographic and clinical data and median polyps diameter between asymptomatic women with normal and abnormal histologic outcome Asymptomatic normal lesions n 1134 Asymptomatic premalignant and malignant lesions n 18 (n 1 cancer a ;n 3 polypoid cancers; n 14 atypical hyperplasias) P value Age, y Parity Age at menopause, y Years of menopause 10 (IR 4-16) 10 (IR 6-17).8 BMI HRT 18% 17%.9 Hypertension 27% 44%.06 Diabetes 4% 11%.1 Median diameter, mm (IR) 11 (8-18) 19 (16-23).0002 BMI, body mass index; HRT, hormone replacement therapy. a The diameter of this single case of cancer on polyps was 40 mm. MARCH 2009 American Journal of Obstetrics & Gynecology 235.e3

4 Research General Gynecology TABLE 3 Descriptive statistics of demographic, clinical data, and diameter of histological abnormal polyps in asymptomatic women Atypical hyperplastic polyp yps were significantly larger, and age and years of menopause were significantly higher in patients with an abnormal outcome. When the 2 groups of patients were compared, no demographic data, clinical characteristic, or polyps diameter proved to be different between asymptomatic women and symptomatic patients with both normal and abnormal histological results. Cancer on glandulocystic polyp Polypoid cancers Number of cases 14 1 a 3 a Age, y /74/57 BMI (IR) 25 (23-28) 30 28/30/33 Years of menopause (IR) 10 (5-16) 18 14/24/6 Hypertension 7 1 HRT 2 Diabetes Median diameter, mm (IR) 19 (17-22) b 40 9/30/25 Serous-papillary/clear cell BMI, body mass index; HRT, hormone replacement therapy. a Data are reported for single cases; b Four cases only were less than 18 mm, the upper quartile of polyps with normal histology. TABLE 4 Descriptive statistics of demographic and clinical data and diameter of polyps in symptomatic patients Atypical hyperplastic polypoid The multivariate logistic regression for all significant or borderline significant variables at univariate analysis proved that, in both asymptomatic women and symptomatic patients, only the diameter of polyps was significantly and independently associated with an abnormal histology (P.05 and P.01, respectively). This finding was replicated in both cohorts when data for age, hypertension, and diameter were categorized Cancer on glandulocystic polypoid Polypoid cancers Number of cases Age, y BMI (IR) 31 (26-39) 27 (26-28) 25 (23-26) Years of menopause (IR) 9 (4-19) 12 (9-20) 14 (11-20) Hypertension HT Diabetes Median diameter, mm (IR) 15 (12-22) 15 (14-17) 19 (14-22) Serous-papillary/clear cell 2 7 BMI, body mass index; HT, hormone therapy. into normal and abnormal using as cutoff the upper interquartile range of normal cases. A mean polyp diameter of 18 mm or greater was the only significant independent variable associated with an abnormal histology (P.03; odds ratio, 6.9; confidence interval, ; P.01; odds ratio, 2.4; confidence interval, , respectively). In asymptomatic cases only 3 uneventful perforations during operative hysteroscopy were observed. Minor complications such as cervical tears and false passages occurred in 7 and 3 cases (0.6 and 0.3%, respectively). In symptomatic cases these rates were 0% and 0.8 %, respectively; no major complications were reported. COMMENT The design of this study addressed a single but well-defined problem: what to do with asymptomatic polyps on atrophic endometrium in postmenopause. These 2 diagnostic characteristics were chosen as entry criteria because they are frequently encountered and are sitting on the safe side of diagnostic accuracy both of transvaginal sonohysterography and office hysteroscopy. 6,8,18,19,21 Women on tamoxifen therapies were excluded. The same criteria were adopted in the parallel cohort of symptomatic patients with abnormal uterine bleeding, whose charts were recruited in the same retrospective period in the 15 centers of the study. The 2 series proved to be not significantly different for demographic and background clinical data. The histological findings on 1152 consecutive polyps hysteroscopically removed in asymptomatic women yielded 1 single case of stage 1 grade 1 endometrial carcinoma on a polyp with a mean diameter of 40 mm. The prevalence was 0.1%. This prevalence was 10 times lower than the prevalence observed in the symptomatic patients. A strict selection of cases should have induced us to exclude cases with a final pathologic report of polypoid carcinoma. However, because polypoid cancers were misdiagnosed as polyps in an equal prevalence by both hysteroscopy and sonohysterography, we decided to 235.e4 American Journal of Obstetrics & Gynecology MARCH 2009

5 General Gynecology Research include these cases to provide a more prudent assessment of the prevalence of oncologic threats posed by the diagnosis of polyps on atrophic endometrium. Again the prevalence of polypoid cancers was 0.3% in asymptomatic women, 10 times lower than in patients with abnormal uterine bleeding. Polypoid cancer added to cancer on polyps up to a prevalence of 0.4% in asymptomatic women. The histotype of the single case of cancer on polyp and the 3 cases of polypoid cancer in asymptomatic women was endometrioid type 1. It is of interest to observe that, opposite of this, 9 of 29 of cases of cancer on polyps and polypoid cancers in symptomatic patients showed a clear cell histotype. This histological characterization is of outmost clinical relevance for the therapeutic and prognostic implication of the 2 neoplasms. The prevalence of atypical hyperplastic (1.2%) polyps was significantly lower in asymptomatic women but only half that of symptomatic patients. We could hypothesize that the progression from atypia to cancer more frequently occurs in association to bleeding episodes of the compact glandular tissue with atypia. Both at univariate and multivariate analysis polyps, diameter was the only variable significantly associated with an abnormal histology (including cancer, polypoid cancer, and atypical hyperplasia) in asymptomatic women. The odd ratio of cancer is 6.9 for polyps with a mean diameter larger than 18 mm. This set cutoff value for the major longitudinal diameter (upper quartile of normal polyps) was adopted for possible clinical use, given the typical ovoid shape of polyps. Polyp diameter was eventually the only significant independent variable retained by multivariate analysis also in symptomatic patients. The odd ratio for polyps greater than 18 mm was 2.4. This low additional risk added by polyp dimension confirms the importance of bleeding rather than dimensions in symptomatic patients. Our findings do not cover the whole range of possible needed information on endometrial polyps as provided by other reported studies 1 that address together pre- and postmenopausal women and low- and high-risk therapies. However, TABLE 5 Univariate analysis for demographic data and median polyp diameter between symptomatic patients with normal and abnormal histologic outcome Symptomatic normal lesions Symptomatic premalignant and malignant lesions P value Number of cases n 724 n 46 Age, y Parity Age at menopause, y Years of menopause (IR) 10 (3-17) 13 (7-21).02 BMI HRT 13% 11%.7 Hypertension 31% 18%.2 Diabetes 6% 6%.9 Median diameter, mm (IR) 13 (9-18) 16 (12-22).01 BMI, body mass index; HRT, hormone replacement therapy. in our opinion the lack of stratification into symptomatic and asymptomatic cases, the inclusion of pre- and postmenopausal cases under the same prevalence analysis, and the absence of information on the coexistence of diffuse endometrial lesion have a negative impact on the clinical use of many reported findings. 4,12,13 Some of these works reported a large data set up to 411 polyps. 4 Unfortunately for the users on the clinical end, the favorable opinion on the removal of asymptomatic polyps is based on only 76 postmenopausal patients. Our findings correspond with and strengthen the findings reported by Shushan et al, 2 Machtinger et al, 5 and Bakour et al. 22 According to these authors who reported altogether 239 asymptomatic polyps, the risk of malignancy in asymptomatic polyps is negligible or null. In our series of asymptomatic polyps, the largest ever analyzed, the prevalence of cancer on polyps is 0.1%. An additional consideration because of guide, a good clinical practice might be derived by the data of Gerber et al, 23 who found that incidental detection of asymptomatic endometrial cancer offers no prognostic advantage over symptomatic disease that had uterine bleeding for shorter than 8 weeks. Possible misclassifications of asymptomatic polyps harboring premalignant or even malignant lesions could be rescued in the following months by clinical signs, and this potential error would not change the prognosis of that single patient. A methodological limit of our work is its multicenter retrospective design. However, the robust definition of the lesion eligible for analysis and the clinical quality of the networking centers coopted for the study under the guidance of the AGUI task force on abnormal uterine bleeding could be claimed to support the reliability of recorded presurgical diagnosis. Discrepancies between diagnostic imaging of the uterine lesion and the final pathologic report, which indeed eventually classified the polyp as a polypoid cancer, probably is related to the realm of clinical practice, and it is probably impossible to look for a better agreement. When we consider this potential diagnostic error, we must restrict the negligible prevalence of malignancy of 0.1% only to those cases in which direct or indirect imaging obtained of the lesion is that of a clear complete typical atrophic fibroglandular polyp (ie, a smooth ovoid lesion); otherwise the potential risk should be moved up to 0.4%. In addition to this, a prudent clinical approach should consider the diameter of the MARCH 2009 American Journal of Obstetrics & Gynecology 235.e5

6 Research General Gynecology polyp to assess the risk of premalignant and malignant polyps: the odds for abnormal findings in an asymptomatic polyp should be multiplied by 6.9 when the mean diameter of the polyp is larger then 18 mm. In conclusion, our data do not support the idea that removal of the typical atrophic fibroglandular polyp on atrophic endometrium is a valid measure for secondary prevention of endometrial cancer. Follow-up and/or treatment of endometrial polyps incidentally diagnosed in asymptomatic postmenopausal patients could be safely restricted to few selected cases based on irregular shape of the lesion and polyp diameter. f REFERENCES 1. Savelli L, De Iaco P, Santini D, et al. Histopathologic features and risk factors for benignity, hyperplasia, and cancer in endometrial polyps. Am J Obstet Gynecol 2003;188: Shushan A, Revel A, Rojansky N. How often are endometrial polyps malignant? Gynecol Obstet Invest 2004;58: Lev-Sagie A, Haman Y, Imba T, Hurwitz A, Lavy Y. The significance of intrauterine lesions detected by ultrasound in asymptomatic postmenopausal patients. BJOG 2005;112: Lieng M, Qvigstad E, Sandvik L, Jorgensen H, Langebrekke A, Istre O. Hysteroscopic resection of symptomatic and asymptomatic endometrial polyps. J Minim Invasive Gynecol 2007;14: Machtinger R, Korach J, Padoa A, et al. Transvaginal ultrasound and diagnostic hysteroscopy as a predictor of endometrial polyps: Risk factors for premalignancy and malignancy. Int J Gynecol Cancer 2005;15: Clark TJ. Outpatient hysteroscopy and ultrasonography in the management of endometrial disease. Curr Opin Obstet Gynecol 2004;16: Dueholm M, Lundorf E, Hansen ES, Ledertoug S, Olesen F. Evaluation of the uterine cavity with magnetic resonance imaging, transvaginal sonography, hysterosonographic examination, and diagnostic hysteroscopy. Fertil Steril 2001; 76: Timmerman D, Verguts J, Konstantinovic ML, et al. The pedicle artery sign based on sonography with color Doppler imaging can replace second-stage tests in women with abnormal vaginal bleeding. Ultrasound Obstet Gynecol 2003;22: Sherman ME, Mazur MT, Kurman RJ. Benign disease of the endometrium. In: Kurman RJ, ed. Blaunstein s pathology of the female genital tract. New York: Springer; p Philip J, Disaia PH, Scott JR. Endometrial pathology. In: Scott JR, Disaia PH, Hammond CB, Spellacy WN, eds. Danforth s obstetrics and gynecology. Philadelphia, PA: Lippincott Co; p Nagele F, O Connor H, Davies A, Badawy A, Mohamed H, Magos A outpatient diagnostic hysteroscopies. Obstet Gynecol 1996;88: Ben-Arie A, Goldchmit C, Laviv Y, et al. The malignant potential of endometrial polyps. Eur J Obstet Gynecol Reprod Biol 2004;115: Goldstein SR, Monteagudo A, Popiolek D, Mayberry P, Timor-Tritsch I. Evaluation of endometrial polyps. Am J Obstet Gynecol 2002;186: Orvieto R, Bar-Hava I, Dicker D, Bar J, Ben- Rafael Z, Neri A. Endometrial polyps during menopause: characterization and significance. Acta Obstet Gynecol Scand 1999;78: Peterson WF, Novak ER. Endometrial polyps. Obstet Gynecol 1956;8: Coeman D, Van Belle Y, Vanderick G, De Muylder X, De Muylder E, Campo R. Hysteroscopic findings in patients with a cervical polyp. Am J Obstet Gynecol 1993;169: Farrell R, Scurry J, Otton G, Hacker NF. Clinicopathologic review of malignant polyps in stage 1A carcinoma of the endometrium. Gynecol Oncol 2005;98: Ferrazzi E, Torri V, Trio D, Zannoni E, Filiberto S, Dordoni D. Sonographic endometrial thickness: a useful test to predict atrophy in patients with postmenopausal bleeding. An Italian multicenter study. Ultrasound Obstet Gynecol 1996;7: Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol 2004;24: Robboy SJ, Anderson MC, Russell P. Endometriosis, metaplasias, polyps and miscellaneous changes. In: Robboy SJ, Anderson MC, Russell P, eds. Pathology of the female genital tract. London: Churchill Livingstone; p Leone FP, Carsana L, Lanzani C, Vago G, Ferrazzi E. Sonohysterographic endometrial sampling and hysteroscopic endometrial biopsy: a comparative study. Ultrasound Obstet Gynecol 2007;29: Bakour SH, Khan KS, Gupta JK. The risk of premalignant and malignant pathology in endometrial polyps. Acta Obstet Gynecol Scand 2000;79: Gerber B, Krause A, Muller H, Reimer T, Kulz T, Kundt G, et al. Ultrasonographic detection of asymptomatic endometrial cancer in postmenopausal patients offers no prognostic advantage over symptomatic disease discovered by uterine bleeding. Eur J Cancer 2001;37: e6 American Journal of Obstetrics & Gynecology MARCH 2009