Hysteroscopy, Transvaginal Ultrasound and Histopathology in Evaluation of Abnormal Uterine Bleeding: Which is Best?

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1 Med. J. Cairo Univ., Vol. 84, No. 2, June: 69-74, Hysteroscopy, Transvaginal Ultrasound and Histopathology in Evaluation of Abnormal Uterine Bleeding: Which is Best? AHMED L. ABU EL NASR, M.D.*; WALID S. EL SHERBINY, M.D.*; TAMER F. TAHA, Ph.D.**; SAMEH H. SALAMA, M.D.** and AHMED A. ABBAS, M.Sc.** The Departments of Obstetrics & Gynaecology*, Faculty of Medicine, Cairo University and Reproductive Health**, National Research Centre, Cairo, Egypt Abstract Background/Aim: Abnormal uterine bleeding in the pre- & postmenopausal women is the most common cause for gynecological referrals. It accounts for up to 33% of patients attending outpatient gynecology outpatient clinics. The popularity of hysteroscopy has been enhanced because it is a simple technique that can be performed in the office. Its specificity and positive predictive value of hysteroscopy is higher than traditional D&C. Hysteroscopy has the advantage of diagnosing focal lesions, particularly pedunculated structures, which are frequently missed by endometrial biopsy or D&C. The present study aimed to compare the efficacy and the acceptability of transvaginal sonography (TVS), hysteroscopy and endometrial biopsy in diagnosis of the various causes of pre- and post-menopausal bleeding. Material and Methods: This study included 50 premenopausal and postmenopausal patients complaining of abnormal uterine bleeding. All of them were subjected to TVS, hysteroscopy and D&C; the results were correlated to the histopathological picture of the endometrium in order to obtain appropriate diagnosis of endometrial lesions. Results: Hysteroscopy was the best tool in detecting endometrial polyp having sensitivity, specificity, PPV and NPV of 100%, 95.8%, 94.7% and 100%, respectively with total accuracy of 97.6%. For submucus myoma hysteroscopy had an accuracy of 100% for all cases diagnosed. For Endometrial hyperplasia hysteroscopy had sensitivity, specificity, PPV and NPV of 90%, 96,8%, 90% and 96.8%, respectively with total accuracy 93.6%. For atrophic endometrium hysteroscopy had 66%, 100%, 100% and 97.5%, respectively with total accuracy of 90.8%. For endometrial carcinoma Hysteroscopy had 50%, 97.5%, 50% and 97.5% with total accuracy of 73.7%. Conclusion: Hysteroscopy could be considered as a gold standard in evaluation of uterine cavity in comparison to TVS & D&C especially in diagnosing endometrial polyps and submucous myoma. D&C and histopathological examination have better accuracy than either hysteroscopy or TVS in Correspondence to: Dr. Tamer F. Taha, Reproductive Health Department, National Research Center, Cairo, Egypt tamtaha2k@yahoo.com diagnosis of hyperplasia and cancer. D&C confirms the diagnosis but can miss focal endometrial lesions. Key Words: Endometrium Hysteroscopy Ultrasound Histo -pathology. Introduction UP to 33% of women referred to gynaecological outpatient clinics have abnormal uterine bleeding and this proportion rises to 69% in a pre-or postmenopausal group. Local causes include fibroids, endometrial polyps, chronic pelvic inflammatory disease, cervical polyps, atrophic vaginitis, endometrial carcinoma and cervical carcinoma [1,2]. Dilation and curettage under general anaesthesia used to be considered the gold standard for the investigation of abnormal uterine bleeding, but it has been shown to be diagnostically inaccurate [3,5] as false negative rates for the detection of pathology at dilation and curettage have been shown to be between 2% and 10% and although considered a routine, minor procedure, up to 5 per 1000 women proceed unexpectedly to a major operation as a result of complications arising from a dilation and curettage [4]. Alternative procedures are available for sampling and/or visualising the endometrial cavity. These vary from endometrial biopsy, with or without vaginal ultrasound in an outpatient clinic, outpatient hysteroscopy in a special clinic, or inpatient admission for hysteroscopy and curettage [5]. The predictive value of hysteroscopy in the investigation of abnormal bleeding has been well documented by several authors and it is considered by many to be the current gold standard investigation of choice [6,7,8]. For lesions as endometrial polyp hysteroscopy has the superiority over other methods in diagnosis and resection of lesions whether as outpatient or inpatient maneuver [8]. 69

2 70 Hysteroscopy, Transvaginal Ultrasound & Histopathology Patients and Methods This study was a prospective study in which 50 patients with abnormal uterine bleeding in the pre and postmenopausal period were recruited from Kasr El Eini and National Reseach Centre Outpatient Gynecology Clinics. The study was conducted between April and December The National Research Centre ethical committee endorsed its approval for the study. All patients gave their written consents to participate in the study. Patients included in the study were women aged 45 years or more with any abnormal vaginal bleeding occurring in pre- and post-menopausal period. Patients with any of the following criteria have been excluded from the study; pregnancy or pregnancy related causes, women received hormone replacement therapy, hormonal contraception or used IUCD within the last 6 months, history of hysteroscopy or fractional curettage in the last 6 month. In addition, women receiving anti-coagulant treatment or diagnosed with active gynaecological infections and virgin patients have been excluded. All eligible patients were subjected to detailed history taking and examination. Conventional two dimensional transvaginal ultrasound (TVS) was performed to measure uterine size, endometrial thickness, and look for any possible pathology such as endometrial polyps or fibroids. This was followed by detailed hysteroscopic examination performed under general anesthesia. Endometrial curettage was done to all patients, and specimens were fixed in Formalin 10% solution for histopathological examination. Patients in whom endometrial polyps were found by hysteroscopy, had polypectomy performed before curettage. All curettage & polypectomy specimens (formalin-fixed, paraffin wax embedded) were subjected to histopathological examination. Statistical analysis: Data were statistically described in terms of frequencies and percentage. Accuracy was represented using the terms of true positive, true negative, false positive, false negative, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall efficacy. Descriptive parametric data was expressed as mean ± Standard deviation (SD) and no parametric data was expressed as number and percentage. The data were tabulated and statistically analyzed to evaluate the differences between the different groups in this study as regard various parameters. Qualitative variables expressed as percentage were compared in the different groups using Kappa test. All statistical calculations were done using computer program Microsoft Excell 2007 and SPSS (Statistical package for the social science, SPSSInc. Chicago, IL, USA) version 15 of Microsoft windows. Results After analyzing our data, we found that 50% of the patients within the study group were postmenopausal while the perimenopausal group were divided into 36% complaining of menometrorrhagia, 10% with menorrhagia and 4% with metrorrhagia. The most common pathological lesions detected were endometrial polyps (38%) followed by endometrial hyperplasia (20%), myoma (16%), atrophic endometrium (4%), endometrial carcinoma (4%) and endometritis (2%). TVS had sensitivity, specificity, PPV and NPV of 72.2%, 96.8%, 92.8% and 96.8%, respectively in relation to hysteroscopy for detection of endometrial polyps with total accuracy of 86.9%. The sensitivity, specificity, PPV and NPV were 90.9%, 94.8%, 83.3% and 97.3%, respectively for with total accuracy of 91.6% for endometrial hyperplasia and 87.5%, 100%, 100% and 97.6%, respectively for with accuracy of 96.3% for submucous myoma. For endometrial carcinoma it showed 50%, 100%, 100% and 97.5%, respectively with total accuracy of 86.8%, while it was 50%, 95.7%, 50% and 95.7%, respectively for atrophic endometrium with total accuracy of 72.8%. In relation to D&C, TVS had sensitivity, specificity, PPV and NPV of 91.6%, 92.1%, 87.5% and 97.2%, respectively for endometrial polyp with total accuracy of 89.8%. Also, it had 75%, 91.8%, 75% and 91.8%, respectively for endometrial hyperplasia with total accuracy of 83.4% and, 100%, 93.8%, 25%, 100%, respectively for atrophic endometrium with total accuracy of 79.7%. While for endometrial carcinoma it showed 50%, 100%, 100% and 97.5%, respectively with total accuracy of 86.8%. Hysteroscopy was the best tool in detecting endometrial polyp having sensitivity, specificity, PPV and NPV of 100%, 95.8%, 94.7% and 100%, respectively with total accuracy of 97.6%. For submucus myoma hysteroscopy had an accuracy of 100% for all cases diagnosed. For Endometrial hyperplasia hysteroscopy had sensitivity, specificity, PPV and NPV of 90%,

3 Ahmed L. Abu El Nasr, et al ,8%, 90% and 96.8% with total accuracy 93.6%. For atrophic endometrium hysteroscopy had 66%, 100%, 100% and 97.5% with total accuracy of 90.8%. For endometrial carcinoma hysteroscopy had 50%, 97.5%, 50% and 97.5% with total accuracy of 73.7%. Table (1): Comparison of Transvaginal ultrasound results in relation to D&C regarding (a), (d), (b), (), sensitivity, specifity, positive predictive value (PPV), predictive value (NPV) and efficacy. Lesion A D B C Sensitivity A/A+Cx 100 Specificity D/D+Bx 100 PPV A/A+Bx 100 NPV D/D+Cx 100 Efficacy Normal % 94.8% 81.8% 94.8% 88.3% Polyps % 92.1 % 78.5% 97.2% 89.8% Hyperplasia % 91.8% 75% 91.8% 83.4% Atrophic % 93.8% 25% 100% 79.7% Cancer % 100% 100% 97.5% 86.8% Foreign body % 100% 100% 100% 100% Table (2): Comparison of Hysteroscopy results in relation to D&C regarding (a), (d), + ve (b), (), sensitivity, specifity, positive predictive value (PPV), predictive value (NPV) and efficacy. Lesion Sensitivity A/A+Cx 100 A D B C Specificity D/D+Bx 100 PPV A/A+Bx 100 NPV D/D+Cx 100 Efficacy Normal % 97.1% 85.7% 97.1% 91.4% Polyps % 95.8% 94.7% 100% 97.6% Hyperplasia % 96.8% 90% 96.8% 93.6 Atrophic % 100% 100% 97.5% 90.8% Cancer % 97.5% 50% 97.5% 73.7% Foreign body % 100% 100% 100% 100% Table (3): Comparison of TVS results in relation to Hysteroscopy regarding (a), (d), (b), (), sensitivity, specifity, positive predictive value (PPV), predictive value (NPV) and efficacy. Lesion A D B C Sensitivity A/A+Cx 100 Specificity D/D+Bx 100 PPV A/A+Bx 100 NPV D/D+Cx 100 Efficacy Normal % 90.2% 63.6% 94.8% 81.5% Polyps % 96.8% 92.8% 86.1% 86.9% Hyperplasia % 94.8% 83.3% 97.3% 91.6% Myoma % 100% 100% 97.6% 96.3% Atrophic % 95.7% 50% 95.7% 72.8% Cancer % 100% 100% 97.5% 86.8% Foreign body % 100% 100% 100% 100% TVS HYS D&C Normal Polyp. Hyperplasia Fibroid Atrophic Cancer Endometritis Foreign body Bar chart showing differences between TVS, Hysteroscopy and D&C.

4 72 Hysteroscopy, Transvaginal Ultrasound & Histopathology Discussion According to our results, hysteroscopy, a low risk procedure involving visualization of endometrial cavity is replacing inpatient dilatation and curettage for evaluation of abnormal uterine bleeding as it is easy to perform, well tolerated by the patient and can identify pathological lesions missed by endometrial biopsy or D&C. In this study, all cases of intra-cavitary uterine fibroid identified by hysteroscopy, thus showing its superiority for diagnosing intra-cavity lesions. For endometrial polyps, hysteroscopy show the highest sensitivity and specificity in relation to D&C being 100%, 95.8% respectively which is close to the study done by Garuti et al. [26] which showed a sensitivity, specificity, NPV and PPV of 95%, 95%, 98% and 81%, respectively. This was superior to TVS which was sensitivity, specificity 91.6%, 92.1% respectively with PPV of 78.5% NPV of 97.2 total accuracy The main drawback of hysteroscopy in diagnosis of endometrial polyp is its lack of histological confirmation as it proved in one case of endometrial polyp diagnosed by hysteroscopy to be malignant by histo pathological lesions and this agreed with Clarck et al. [18] where endometrial biopsy whether blind or eye-directed hysteroscopic guided was the most sensitive technique for diagnosis of hyperplasia and carcinoma when compared with TVS and hysteroscopy. As regarding myoma, hysteroscopy not only diagnosed accurately all cases of myoma but also could establish diagnosis of one case which was misdiagnosed by TVS as endometrial Polyp giving sensitivity, specificity of 100% while TVS sensitivity, specificity were 87.5%, 100% respectively with PPV 100%, NPV 97.6% and total accuracy 96.3%. These results are close to Fedele et al. [25] which has shown sensitivity of 88% and specificity of 94% for diagnosing fibroid. As regarding detecting normal endometrium, Hysteroscopy shows the highest sensitivity & specificity in detecting normal from abnormal endometrium. This came in accordance with Garuti et al. [26] who showed overall sensitivity and specificity of hysteroscopy as 94% and 89%, respectively for predicting normal and abnormal histopathology of endometrium, with highest accuracy in diagnosing polyps with sensitivity, specificity, NPV and PPV of 95%, 95%, 98% and 8 1 %, respectively which is comparable to our results. The least accuracy of hysteroscopy was in detection of endometrial carcinoma with sensitivity, specificity 50%, 97.5%, respectively. These results were less than but corresponding with Christine de Berg [8] which has shown a sensitivity of 86.4% and specificity of 99.2% for adenocarcinoma but disagree with Clarck TJ et al. [18] which has shown sensitivity, specificity, NPV and PPV of 100%, 98%, 100% and 33%, respectively regarding hysteroscopy in diagnosis of adenocarcinoma. This can be explained by the similarity of appearance of lesions in some cases between hyperplasia and early carcinoma, also the development of malignant focal foci within hyperplasia or on top of other associated lesions like polyps. TVS had better sensitivity and specificity in the diagnosis of cancer This can be due to that TVS alone can be used to evaluate pre-malignant lesions and endometrial thickness, Yet, confirming development of malignancy requires further methods. Also, as regard to endometrial hyperplasia TVS alone show moderate sensitivity and specificity. These results improved when combined with hysteroscopy. This corresponds with the study done by Gull et al. [27] which have shown sensitivity and specificity being 97%, 88%, respectively. D&C was the most sensitive technique for diagnosis of hyperplasia and carcinoma when compared with TVS and hysteroscopy and this agreed with Leuchter et al. [29] where D&C was the most sensitive technique for diagnosis of hyperplasia and carcinoma when compared with TVS and hysteroscopy. In contrast, Sunita et al. [31] concluded a higher sensitivity of hysteroscopy over D&C in evaluating hyperplasia and cancer. This can be due to the better eye-directed evaluation of lesions by hysteroscopy of suspicious lesions rather than the blind D&C, which can miss isolated focal malignant foci within endometrium. For atrophic endometrium, hysteroscopy has the highest sensitivity and specificity for detecting small local lesions within atrophic endometrium which were missed with blind D&C. The less PPV on using TVS alone is due to the lack of the ability to visualize minute lesion with possible biopsy taken which overcome proper detection of small hidden lesions within atrophic endometrium like polyps or malignant foci. The higher sensitivity of hysteroscopy over D&C or TVS alone demonstrates the routine D&C for post-menopausal bleeding with atrophic endometrium can be avoided for the advance of hysteroscopy. Also, demonstrates that thin endometrium less than 4mm in post menopausal women was inconclusive for evaluation of uterine cavity in cases of bleeding. These results

5 Ahmed L. Abu El Nasr, et al. 73 correlated with Pyari et al. [30] who showed sensitivity, specificity, NPV and PPV of 89%, 96%, 100% and 97%, respectively for diagnosing atrophic endometrium. Conclusion: TVS alone is less accurate than hysteroscopy in detecting intra-cavitary lesions also TVS alone is less accurate than hysteroscopy and pathological examination in evaluation of postmenopausal bleeding with thin endometrium. Hysteroscopy is the most accurate tool of diagnosis of intra-cavitary lesions as endometrial polyps and submucous myoma. The main drawback of findings detected by hysteroscopy is the necessity of histo pathological examination to confirm diagnosis. However, D&C is still having better accuracy than hysteroscopy and TVS in diagnosis of hyperplasia and cancer. Conflict of interest: Authors declared no conflict of interest. References 1- ALEEM F., PREDANIC M., CALAME R., MOUKHTAR M. and PENNISI J.: Transvaginal color and pulsed Doppler sonography of the endometrium: A possible role in reducing the number of dilatation and curettage procedures. J. Ultrasound Med., 14: , ALFEU CORNÉLIO A.N., WAGNER J.G., SERGIO NICOLAU M., JOSE M., MAURO ABI HAIDER, GER- ALDO R. and EDMUND C.B.: Comparisonbetween hysterosonography, hysteroscopy and histopathology in the evaluation of postmenopausal womenuterine cavity. Rev. Bras Gynecol. Obstet., 25-29, ANGIONI S., LODDO A., MILANO F., PIRAS B., MIN- ERBA L. and MELIS G.B.: Detectionod benign intracavitary lesions in postmenopausal women with abnormal uterine bleeding: A prospective comparative study on outpatient hysteroscopy and blind biopsy. J. Minimally Invasive Gynecol., 15: 87-91, BAGGISH M.S., GUEDJ H. and VALLE R.F.: Hysteroscopy: Visual perspectives of uterine anatomy, physiology and pathology. Wolters Kluwer Health/Lippincott Williams & Wilkins, BAKOUR S.H., KHAN K.S. and GUPTA J.K.: The risk of premalignant and malignant pathology in endometrial polyps. Acta. Obstet. Gynecol. Scand, 79: , BARBOT J., PARENT B. and DUBUISSON J.B.: Contact hysteroscopy: Another method of endoscopic examination of the uterine cavity. Am. J. Obstet. Gynecol., Mar 15, 136 (6): , BELL S.W., KEMPSON R.L. and HENDRICKSON M.R.: Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am. J. Surg. Pathol., June, 18 (6): , BERG C.D.: Is hysteroscopy an accurate diagnostic tool? J. Watch Women's Health, 1204: 1209, BETTOCCHI S. and SELVAGGI L.: A vaginoscopic approach to reduce the pain of office hysteroscopy. J. Am. Assoc. Gynecol. Laparosc., Feb. 4 (2): , BIRINYI L., DARAGO P., TOROK P., CSISZAR P., MAJOR T., BORSOS A., et al.: Predictive value of hysteroscopic examination in intrauterine abnormalities. Eur. J. Obstet. Gynecol. Reprod Biol., 115: 75-79, BONNAMY L., MARRET H., PERROTIN F., BODY G., BERGER C. and LANSAC J.: Sonohysterography: A prospective survey of results and complications in 81 patients. Eur. J. Obstet. Gynecol. Reprod Biol., 102: 42-47, BURBOS N., MUSONDA P., GIARENIS L., et al.: Agerelated differential diagnosis of vaginal bleeding in postmenopausal women: A series of 3047 symptomatic postmenopausal women. Menopause International, 16: 5, BRADLEY L.D.: Overview of Hysteroscopy. Up To Date. Available at: top ic. do?top ickey=gyn_surg/ &view=print 14- BREIJER M., TIMMERMANS A., et al.: Review Article: Diagnostic Strategies for Postmenopausal Bleeding. Obstetrics and Gynecology International, Article ID , CACCIATORE B., RAMSAY T., LEHTOVIRTA P. and YLOSTALO P.: Transvaginal sonography and hysteroscopy in postmenopausal bleeding. Acta. Obstet. Gynecol. Scand., 73: , CEPNI I., OCAL P., ERKAN S., SARICALI F.S., AKBAS H. and DEMIRKIRAN F.: Comparison of transvaginal sonography, saline infusion sonography and hysteroscopy in the evaluation of uterine cavity pathologies. Aust. NZ J. Obstet. Gynaecol., 45: 30-35, CICINELLI E., DIDONNA T., SCHONAUER L.M., STRAGAPEDE S., FALCO N. and PANSINI N.: Paracervical anesthesia for hysteroscopy and endometrial biopsy in postmenopausal women. A randomized, double-blind, placebo-controlled study. J. Reprod Med., Dec. 43 (12): , CLARK T.J., VOIT D., GUPTA J.K., HYDE C., SONG F. and KHAN K.S.: Accuracy of hysteroscopy in the diagnosis of endometrial cancer and hyperplasia: A systematic quantitative review. JAMA, 288: , COOPER J.M. and ERICKSON M.L.: Endometrial sampling technique in the diagnosis of abnormal uterine bleeding. Obstetrics and Gynecoology Clinics of North America, 27 (2): , CREASMAN W.T.: Endometrial cancer: incidence, prognostic factors, diagnosis, and treatment. Semin Oncol., Feb., DESSOLE S., CAPOBIANCO G. and AMBROSINI G.: Endometrial polyps during menopause: Characterization and significance. Acta. Obstet. Gynecol. Scand, 79 (10): 902, De WIT A.C., VLEUGELS M.P. and de KRUIF J.H.: Diagnostic hysteroscopy: A valuable diagnostic tool in the diagnosis of structural intra-cavital pathology and endometrial hyperplasia or carcinoma?. Six years of

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