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2 Author's personl copy Interntionl Journl of Gynecology nd Obstetrics 123 (2013) Contents lists vilble t ScienceDirect Interntionl Journl of Gynecology nd Obstetrics journl homepge: CLINICAL ARTICLE Endometril polyp size nd polyp hyperplsi Bernrdo P. Lsmr, Ricrdo B. Lsmr Deprtment of Mternl nd Child Helth, Federl Fluminense University, Niterói, Brzil rticle info bstrct Article history: Received 20 Februry 2013 Received in revised form 7 June 2013 Accepted 27 August 2013 Keywords: Endometril polyps Hyperplsi Hysteroscopy Polyp sizes Objective: To ssess the correltion between the size of endometril polyps nd the histopthologic dignosis of hyperplsi or cncer. Methods: A retrospective study ws conducted using dtbses of the outptient clinic t Antonio Pedro University Hospitl in Niterói, Brzil, nd of privte hysteroscopy service. The nlysis included 1136 symptomtic ptients with n endometril polyp identified on hysteroscopy, with pthologic exmintion, during the period The polyp size, the ptients ge, the indiction for hysteroscopic exmintion, nd the use of hormone mediction were compred with the finding of hyperplsi in the pthologic exmintion. Results: Only polyp size showed sttisticl significnce mong the vribles nlyzed (P b 0.05). Endometril polyps greter thn 15 mm showed hyperplsi rte of 14.8%, compred with 7.7% in the group with smller polyps (P b 0.05). Conclusion: Endometril polyps mesuring more thn 15 mm were ssocited with hyperplsi Interntionl Federtion of Gynecology nd Obstetrics. Published by Elsevier Irelnd Ltd. All rights reserved. 1. Introduction Endometril polyp is benign disese tht ffects pproximtely 25% of women [1,2]. It comprises strom, glnds, nd vessels. It is generlly symptomtic nd is dignosed in routine exms, but it my lso be relted to bnorml uterine bleeding, infertility, nd premlignnt or mlignnt endometril lesions. Endometril polyps re present in 13 50% of women with bnorml uterine bleeding [2,3]. The origin nd pthogenesis of endometril polyps re not well known, nd some fctors such s dvnced ge, polyp size, nd ssocited bleeding might be relted to progression to mlignnt lesion. The prevlence of mlignnt lesions mong endometril polyps vries from 1% to 3% [2]. The brod use of ncillry tests, such s trnsvginl ultrsound, in the gynecologic workup hs incresed the presumptive dignosis of endometril polyps in symptomtic women [1,2]. The evidence is controversil regrding tretment of these lesions [1,2,4 6]. Although hysteroscopic polypectomy is sfe, there is trend in the literture [1,5,7] to support conservtive tretment (wtchful witing) for 1 yer if the polyp is smller thn 15 mm nd the ptient is symptomtic nd hs no risk fctors for mlignncy. This is justified by the high rte of remission of smll polyps, nd there is virtully no progression to mlignncy in such cses [2,8]. The risk fctors for mlignncy re high body mss index, rteril hypertension, dvnced ge, postmenopusl period, nd use of tmoxifen [8 10]. Hypertension nd dibetes mellitus, lthough being considered risk fctors for endometril crcinom, were not ssocited with mlignnt trnsformtion of endometril polyps in severl studies [11 13].In Corresponding uthor t: Ru Mrques do Prn 303, Niterói, Rio de Jneiro , Brzil. Tel./fx: E-mil ddress: bernrdo@lsmr.com.br (B.P. Lsmr). survey of 766 ptients with n endometril polyp, Wng et l. [11] identified the following risk fctors for mlignncy: menopusl sttus, size of endometril polyps lrger thn 1 cm, nd presence of bnorml uterine bleeding. Hypertension, dibetes mellitus, body mss index, nd use of tmoxifen were not ssocited with the mlignnt trnsformtion of polyps. In retrospective nlysis of 394 ptients with endometril polyps [12], only ge emerged s risk fctor for mlignncy rising in endometril polyps fter multivrite logistic regression. Dibetes nd hypertension were not ssocited with mlignnt trnsformtion; polyp size ws not included in the nlysis. Trnsvginl ultrsonogrphy is method with high sensitivity nd specificity in the dignosis of endometril polyps. The combintion with color Doppler imging increses the dignostic cpcity of the method, enbling the identifiction of single feeding vessel, which is typicl of endometril polyps [14]. Severl uthors [15 18] hve ttempted to correlte power Doppler fetures with the histopthologic chrcteristics of hyperplsi or cncer ssocited with endometril polyps. However, there ws no ssocition between the pulstility index or resistive index nd histopthologic findings. Thus, the Doppler study of endometril polyps does not replce pthology, with biopsy being mndtory in cses of suspected mlignncy [18]. The objective of the present study ws to ssess the correltion between endometril polyp size nd histopthologic dignosis of hyperplsi or cncer in symptomtic ptients t mencme who hd dignosis of endometril polyp on hysteroscopy. 2. Mterils nd methods A retrospective study of symptomtic ptients t mencme (ge yers) with hysteroscopic dignosis of endometril polyp ws conducted. The dt were retrieved from dtbses of the outptient /$ see front mtter 2013 Interntionl Federtion of Gynecology nd Obstetrics. Published by Elsevier Irelnd Ltd. All rights reserved.

3 Author's personl copy B.P. Lsmr, R.B. Lsmr / Interntionl Journl of Gynecology nd Obstetrics 123 (2013) clinic t Antonio Pedro University Hospitl (Federl Fluminense University) in Niterói, Brzil, nd of privte hysteroscopy service (Ginendo Clinic) in Rio de Jneiro from Jnury 1, 1999, to December 31, The initil study dtbse contined informtion on hysteroscopies of ptients ged between 15 nd 98 yers (Fig. 1). Ptients were excluded if they were older thn 52 yers, hd ny symptoms (bdominl pin, dysmenorrhe, bnorml uterine bleeding) t presenttion, hd reched menopuse, hd colpocytologicl chnges, or hd no endometril polyp identified upon hysteroscopy. After exclusions, 1720 exmintions were vilble. Of these, 491 were excluded for not contining description on polyp size, nd 93 were excluded becuse of bsent or inconclusive pthologic reports. The finl nlysis included 1136 hysteroscopies. The project ws pproved by the Reserch Ethics Committee of Antonio Pedro University Hospitl/Federl Fluminense University. Informed consent ws not needed becuse the study hd retrospective design nd ll ptients hd forml hysteroscopy indiction. Ptients with infertility were not excluded from the study. Although infertility is forml indiction for polypectomy, it is not considered to be risk fctor for endometril polyp hyperplsi. Other indictions for hysteroscopy included endometritis follow-up, intruterine device removl, endocervicl polyp t speculum exmintion, nd hysteroscopic control fter myomectomy. The dt collected from ech ptient included ge, prity, lst menstrul period, indiction of hysteroscopy, complint of the ptient, use of medictions, imging exm findings, nd histopthology (in cse of biopsies or complete excision of the lesion). The size of the endometril polyp ws defined by hysteroscopy. In cse of multiple polyps, the size of the polyp submitted to biopsy ws used in the nlysis. All hysteroscopies were performed t the outptient clinic, with no nlgesi, using 2.9-mm scope with 5-FR internl sheth for the opertive chnnel nd liquid distension medium (sline solution). All biopsies were guided (performed under direct view) using 5-FR forceps. To fcilitte dt nlysis, the women were divided into groups ccording to ge (less thn 30 yers, yers, nd over 40 yers), polyp size (up to 15 mm nd greter thn 15 mm), nd pthologic results (hyperplstic nd non-hyperplstic polyps). The χ 2 test ws used s the sttisticl test, with P b 0.05 considered to be sttisticlly significnt. The sttisticl softwre used ws Stt 8.0 (SttCorp, College Sttion, TX, USA). 3. Results A totl of 1136 hysteroscopies were included in the study. Most ptients (962 [84.7%]) were not tking hormone mediction; 11 (1.0%) received tmoxifen s djuvnt tretment for brest cncer (Tble 1). The disese most often ssocited with endometril polyp nd identified on hysteroscopy ws endocervicl polyp, present in 294 (25.9%) women. The min indiction for undergoing hysteroscopy ws n ultrsound finding of polyp or endometril thickening (n = 732 [64.4%]). The men ge of the prticipnts ws ± 6.32 yers (rnge yers) nd the men polyp size ws ± 6.40 mm (rnge 1 50 mm). Of the 1136 endometril polyps submitted to biopsy or excision t the outptient clinic, 102 were clssified s hyperplstic upon pthologic exmintion. The men size of the hyperplstic polyps ws ± 6.39 mm (rnge 5 35 mm), compred with mm for the nonhyperplstic polyps. The men ge of women with hyperplstic endometril polyp ws 40.5 ± 6.54 yers (rnge yers). Ten (9.8%) ptients received hormonl contrceptives nd none received tmoxifen. Most endometril polyps (926 [81.5%]) mesured up to 15 mm nd 210 (18.5%) were greter thn 15 mm. Ultrsound ws the min indiction for hysteroscopy in women with lrger polyps (Tble 2). Among the women with polyp up to 15 mm, infertility ws common indiction for the hysteroscopy, but ultrsonogrphy ws the primry hysteroscopies 7030 women ged >52 yers hysteroscopies 3874 women with cytopthologic chnges or symptoms 8891 symptomtic or infertile women 7171 hysteroscopies with no dignosis of endometril polyp 1720 women in mencme with endometril polyp 93 women with inconclusive or bsent histopthologic report 491 hysteroscopies with no record of polyp size 1136 women selected Fig. 1. Ptient selection.

4 Author's personl copy 238 B.P. Lsmr, R.B. Lsmr / Interntionl Journl of Gynecology nd Obstetrics 123 (2013) Tble 1 Chrcteristics of symptomtic ptients ged up to 52 yers with n endometril polyp on hysteroscopy (n = 1136). Prmeter Number (percentge) Age, y b30 65 (5.7) (48.9) (45.4) Prity Nulliprous 512 (45.1) Up to 2 deliveries 450 (36.6) 3 deliveries 174(15.3) Abortion (71.5) (18.8) 2 80 (7.1) 3 19 (1.7) N3 11 (1.0) Hormonl contrceptive Yes 174 (15.3) No 962 (84.7) Other ssocited conditions No conditions 661 (58.2) Endocervicl polyp 294 (25.9) Endometril hypertrophy 116 (10.2) Myom 52 (4.6) Adenomyosis 13 (1.1) Indiction for hysteroscopy Ultrsound 732 (64.4) Infertility 349 (30.7) Other b 55 (4.8) Tmoxifen Yes 11 (1.0) No 1125 (99.0) b Other indictions included endometritis follow-up, intruterine device removl, endocervicl polyp t speculum exmintion, nd hysteroscopic control fter myomectomy. indiction. In the group with lrger polyps, the hyperplsi rte ws 14.8%, compred with 7.7% in the group with smller polyps (P b 0.05) (Tble 3). When the cut-off point for endometril polyp size ws chnged to 10 mm, hyperplsi ws found in 37 (7.2%) of the polyps up to 10 mm compred with 65 (10.4%) of the polyps greter thn 10 mm. The difference ws not sttisticlly significnt (P =0.064). Among the 1136 cses ssessed, there ws only 1 (1.0%) cse of premlignnt lesion (simple hyperplsi with typi) in 40-yer-old ptient using norethisterone. The size of this endometril polyp on hysteroscopy ws 10 mm. The ge of the ptients showed no reltion with the presence of hyperplsi in the polyp (P N 0.05) (Tble 4). 4. Discussion The development of n endometril polyp cn be ssocited with rteril hypertension, dibetes mellitus, nd the presence of endocervicl polyps [2,8]. In the present study, 25.9% of the ptients hd n ssocited endocervicl polyp. The study did not ssess the ssocition with dibetes mellitus nd hypertension becuse this informtion ws not vilble. Tble 3 Correltion between polyp size nd histopthology. Polyp size, mm Endometril polyp Hyperplstic endometril polyp P vlue b 15 (n = 926) 855 (92.3) 71 (7.7) b0.001 N15 (n = 210) 179 (85.2) 31 (14.8) b0.001 Totl (n = 1136) 1034 (91.0) 102 (9.0) b Person χ 2 = The size of the endometril polyp seems to be n importnt risk fctor for premlignnt/mlignnt progression of the disese. Some uthors [2,19] hve suggested cut-off point of 10 mm in ptients with no bnorml uterine bleeding, wheres others [9] hve mentioned 15 mm. In the present series, the men size of hyperplstic polyps ws mm, compred with mm for the nonhyperplstic polyps. The usefulness of other tools such s Doppler ultrsonogrphic exmintion to predict the risk of mlignncy hs not yet been estblished [8,11]. The vst mjority of simple hyperplsi cses occurred in polyps greter thn 15 mm, corroborting previous findings [2,8 11] tht conservtive follow-up in ptients with smll symptomtic polyps is sfe. When setting the cut-off point for polyp size t 10 mm, the incidence of hyperplsi ws higher in lrger polyps (10.4% versus 7.2%), but the difference ws not sttisticlly significnt, supporting the need for clinicl follow-up of these polyps. Although tmoxifen might be ssocited with the development of typicl hyperplsi [8], there ws no such ssocition in the present study. This my be explined by the smll proportion of ptients (1.0%) receiving tmoxifen in the smple. There ws no reltion between the ptients ge nd the incidence of hyperplsi in endometril polyps. This my be relted to the decision to set the mximum ge t 52 yers. On the other hnd, the min risk fctor for mlignncy in postmenopusl women is uterine bleeding nd not ge [9]. Hysteroscopic polypectomy is the gold stndrd method to excise endometril polyps [19 21]. The literture corrobortes conservtive mngement for smll (less thn 10 mm) nd symptomtic polyps, with high evidence level (level A) [8,19,21], the regression rte being up to 25% [2,8]. However, infertile, symptomtic ptients should undergo polypectomy to enble better response to nturl or ssisted conception (level A) [19]. In symptomtic ptients, polypectomy should be performed to resolve symptoms nd, especilly in postmenopusl women, to exmine the lesion histologiclly [19]. At the outptient clinic where the study took plce, hysterectomy is routinely performed using sheth with n opertive chnnel; hence, whenever possible, biopsy or exeresis of the lesion is performed simultneously with the dignostic exmintion. Although the dt indicte different pproch, we hve lwys chosen to perform polypectomy for smll polyps (less thn 10 mm) with pedicles, becuse the lesion cn be crefully removed by directing the biopsy to the lesion s bse. Guided biopsy of the lesion is mndtory becuse even smll polyps in symptomtic women my be hyperplstic [22,23]. Office polypectomy is secure procedure with low compliction rtes nd should lwys be performed when possible, thereby voiding further screening tht would be required with conservtive pproch. Tble 2 Correltion between polyp size nd indiction of hysteroscopy. Polyp size, mm Ultrsound Infertility Other P vlue b 15 (n = 926) 556 (60.0) 323 (34.9) 47 (5.1) b0.001 N15 (n = 210) 176 (83.8) 26 (12.4) 8 (3.8) b0.001 Totl (n = 1136) 732 (64.4) 349 (30.7) 55 (4.8) b Person χ 2 = Tble 4 Correltion between ptient ge nd histopthology of endometril polyps. Age, y Endometril polyp Hyperplstic endometril polyp P vlue b b30 (n = 65) 58 (89.2) 7 (10.8) (n = 555) 511 (92.1) 44 (7.9) N40 (n = 516) 465 (90.1) 51 (9.9) Totl (n = 1136) 1034 (91.0) 102 (9.0) b Person χ 2 =

5 Author's personl copy B.P. Lsmr, R.B. Lsmr / Interntionl Journl of Gynecology nd Obstetrics 123 (2013) Despite the lrge number of ptients in the present study nd the fct tht biopsies were guided to res of mjor chnges in the polyp, the results might hve been influenced by the use of biopsies rther thn whole lesions for the pthologic exmintion. Further studies, preferbly with prospective design, should be crried out to evlute the prevlence of premlignnt/mlignnt lesions in symptomtic postmenopusl ptients. It should lso be ssessed whether the vsculr pttern of the polyp nd the condition of the endometrium (thickness, irregulrity) re ssocited with the risk of hyperplsi. According to the present study, it is sfe to perform wtchful witing in symptomtic women in mencme with n endometril polyp smller thn 15 mm, s corroborted by the literture [2,19,24,25]. Endometril polyps greter thn 15 mm were ssocited with higher rte of hyperplsi. Conflict of interest The uthors hve no conflicts of interest. References [1] Perez-Medin T, Mrtinez O, Folgueir G, Bjo J. Which endometril polyps should be resected? J Am Assoc Gynecol Lprosc 1999;6(1):71 4. [2] Lieng M, Istre O, Sndvik L, Qvigstd E. Prevlence, 1-yer regression rte, nd clinicl significnce of symptomtic endometril polyps: cross-sectionl study. J Minim Invsive Gynecol 2009;16(4): [3] Lsmr RB, Brrozo PR, Prente RC, Lsmr BP, d Ros DB, Penn IA, et l. Hysteroscopic evlution in ptients with infertility. Rev Brs Ginecol Obstet 2010;32(8): [4] Rckow BW, Jorgensen E, Tylor HS. Endometril polyps ffect uterine receptivity. Fertil Steril 2011;95(8): [5] Lsmr RB, Dis R, Brrozo PR, Oliveir MA, Coutinho Ed S, d Ros DB. Prevlence of hysteroscopic findings nd histologic dignoses in ptients with bnorml uterine bleeding. Fertil Steril 2008;89(6): [6] Cost-Piv L, Godoy Jr CE, Antunes Jr A, Cseiro JD, Arthuso M, Pinto-Neto AM. 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