ABSTRACT

Objective:

In this study, we aimed to compare the endometrial suction biopsy with Pipelle^® and endometrial curettage (D&C) findings from patients with abnormal uterine bleeding and/or endometrial thickness to observe the possible influencing factors on ESB’s diagnostic value.

Method:

In Tekirdağ Community Hospital and Gynecology Clinic, data were retrospectively collected from hospital registry. 122 patients who had abnormal uterine bleeding and/or endometrial thickness were selected and from all cases, endometrial biopsies were taken with Pipelle^® and D&C methods at the same time. In conclusion, pathologic results of two methods were compared.

Results:

Pathology results were as follows: By Pipelle^®, 44 patients (36.1%) were found with endometrial polyp, 26 patients (21.3%) with endometrial atrophy, 31 patients (25.4%) with proliferative endometrium, 11 patients (9%) with secretory endometrium, 4 patients (3.3%) with endometrial carcinoma, 1 patient (0.8%) with hyperplasia without atypia, 2 patients (1.6%) with inflammation; by D&C, 55 patients (45.1%) were found with polyp, 20 patients (16.4%) with endometrial atrophy, 34 patients (27.9%) with proliferative endometrium, 9 patients (7.4%) with secretory endometrium, 4 patients (3.3%) with endometrial carcinoma, 1 patient (0.8%) with hyperplasia without atypia, 2 patients (1.6%) with inflammation. Correlations between two methods were found as 97.6%, 95.3%, 91.7%, 98.3%, 100%, 100%, and 100% for proliferative endometrium, atrophy, polyp, secretory endometrium, endometrial cancer, hyperplasia without atypia and inflammation, respectively. Discorrelations between two diagnostic methods were more commonly seen in endometrial polyp pathology.

Conclusion:

Our study findings revealed very high correlations between the pathology results of Pipelle^® and D&C procedures. Pipelle^®, with the advantages of being a simple outpatient procedure and having less complication rates, can be preferred over D&C reliably in most clinic situations. On the other hand, D&C method should be preferred in cases of endometrial polyp pathologies due to increased discorrelation rates and biopsy failures in Pipelle^® biopsy.

Introduction

Endometrial sampling is a valuable procedure in routine gynecology practice with its diverse advantages in differentiating malignant-premalignant lesions, excision of certain lesions, observing the cyclic hormonal effects and being simple feasible method. Sampling can be achieved by endometrial suction biopsy (ESB), dilatation and curettage (D&C) and hysteroscopic biopsies.

Ultrasonography and hysteroscopy are among valuable imaging methods for diagnosing uterine and endometrial pathologies. Endometrium, cervix, uterus and adnexa can easily be evaluated by transvaginal ultrasonography, which is a frequently preferred non-invasive method. On the other hand, the minimally invasive method, saline infusion sonography is superior to traditional ultrasonography in detecting small focal endometrial lesions (1).

Hysteroscopy is the gold standard method for visualizing focal intrauterine lesions. Diagnostic accuracy of endometrial biopsies is increased when performed during hysteroscopy (2). Not requiring anesthesia, diagnostic hysteroscopies became a practical and reliable outpatient office procedure.

Endometrial sampling is the gold standard diagnostic method for the most patients with abnormal uterine bleeding complaint (3). The most common such clinical scenarios are postmenopausal bleeding, postmenopausal endometrial thickening, and perimenopausal menometrorrhagia (>45 years of age). Endometrial polyps, atrophy, hormonal, inflammatory, premalignant and malignant differentiations are among the important pathological findings that can be reported. Dilatation and curettage (D&C) is an invaluable diagnostic method for endometrial pathologies. However, due to its need for anesthesia, risk for uterine perforation and post-procedure adhesions, ESB is commonly preferred over D&C in routine gynecology practice (4).

A diagnostic method’s accuracy is measured by comparing its correct diagnoses by those of gold standard method, which sometimes can depend on different target group characteristics. In addition, practicality and cost-effectivity are important aspects of a diagnostic method on the way of being “gold standard”. ESB by Pipelle^® has been shown to be cost-effective in diagnosing endometrial cancer among patients with postmenopausal bleeding (5).

In this study, because it has been suggested as practical and cost-effective method, we aimed to evaluate diagnostic reliability of Pipelle^® biopsy, and to further delineate the possible factors causing inconsistent results when compared to D&C method.

Materials and Methods

Prior to the study, Namık Kemal University Faculty of Medicine Clinical Research Ethical Board approval was obtained (Document number 2020.87.04.11, April 30^th, 2020). One hundred and twenty-two patients’ pathology reports of endometrial samplings done via concurrent Pipelle^® biopsy and D&C methods were retrospectively collected from medical records of Department of Obstetrics and Gynecology at Namık Kemal Community Hospital.

Statistical Analysis

Statistical analyses were performed by using SPSS-20 software. Demographic characteristics and endometrial thickness values were analyzed. Categorical variables were given as numeric and percentages. By calculating consistency rates for sensitivity, specificity, negative and positive predictive values, Pipelle^® biopsy’s diagnostic accuracy was determined in this cohort.

Prior to the procedures, routine gynecologic evaluation by speculum, bimanual exam and transvaginal ultrasonography was completed. Also, complete blood count, liver and renal function tests, serum b-hCG, basic coagulation tests, and serum work-up for hepatitis B, C, and HIV were done. Inclusion criteria were postmenopausal bleeding, postmenopausal endometrial thickening (>5 mm), menorrhagia, metrorrhagia and focal endometrial lesion on a transvaginal ultrasonography. Exclusion criteria were history of previous hormonal therapy or intrauterine surgery. Since general anesthesia is not given in endometrial biopsy procedures in our clinic, in order to evaluate the pain tolerance and cervical stenosis condition during the procedure, it is a long-standing method in our clinic to perform the endometrial biopsy procedures with Pipelle^® or a 4.5 mm 00 number sharp curette before the D&C procedure. Only cases whose Pipelle^® biopsy and D&C samples were evaluated by the same gyneco-pathologist were included in this study. Pipelle^® biopsy’s competency was decided by comparing its results to that of standard D&C method.

Results

After applying the inclusion and exclusion criteria, the data from the cohort of 122 patients were reviewed. The median age was 48.3±8.7 years. There were 80 (65.6%) premenopausal and 42 (34.4%) postmenopausal patients. The median values were 3.2±2.2 for gravida and 2.5±1.4 for parity. The mean body mass index (BMI) was calculated as 29.6±6.1 (Table 1). Pipelle^® biopsy results were as follows: 44 cases with polyps (36.1%), 26 with atrophy (21.3%), 34 with proliferative endometrium (27.9%), 11 with secretory endometrium (9.0%), 4 with carcinoma (3.3%), 1 with hyperplasia without atypia (0.8%), and 2 with inflammation result (1.6%) (Table 2).

Table 1

Table 2

D&C results were as follows: 55 cases with polyps (45.1%), 20 with atrophy (16.4%), 31 with proliferative endometrium (25.4%), 9 with secretory endometrium (7.4%), 4 with carcinoma (3.3%), 1 with hyperplasia without atypia (0.8%), 2 with inflammation result (1.6%) (Table 2). Sensitivity, specificity, positive and negative predictive value of tests were measured, concordance rate was calculated for proliferative endometrium, atrophy, polyp, secretory endometrium, endometrial cancer, non-atypical hyperplasia and inflammation at the rates of 97.6%, 95.3%, 91.7%, 98.3%, 100%, 100%, and 100%, respectively (Table 3).

Table 2

Table 3

Discussion

In this study, our findings supported that, instead of D&C, a practical endometrial biopsy method Pipelle^®s can be utilized in many clinical situations where uterine pathologies are searched for. In endometrial polyps and atrophies, acceptable inconsistency rates were observed while remarkably high consistency rates were found with the rest of the compared uterine pathologies.

Pipelle^® biopsy is a valuable method that provides low false negative results especially in cases with endometrial cancer and atrophy (6). On the other hand, some factors can cause failures such as less than 4 mm endometrial thickness, inflammation, polyps, and submucous myomas (7). In some reports, hysteroscopic sampling was found to have lower sensitivity than Pipelle^® biopsy and D&C methods, implying the leakage of endometrial cells along with hysteroscopic media (8).

D&C is the gold standard for diagnosing endometrial tissue pathologies (9). However, due the need for anesthesia, postoperative pain and relatively higher rate of complications, alternative diagnostic methods have been developed.

Pipelle^® biopsy is an invaluable minimally invasive diagnostic method which provides sampling adequacy over 98% when endometrial thickness is over 5 mm (10). Interestingly none of our 12 cases with less than 5 mm endometrial thickness had result failure.

Piatek et al. (11) reported the sampling adequacy as 82.3% and 84.1% for Pipelle^® biopsy and D&C methods, respectively. They observed that the highest sampling adequacy was in patients with abnormal uterine bleeding (88.8%) and lowest in patients with “abnormal endometrial imaging” indications (37%).

The most frequent factors associated with failure to report in D&C specimens were reported as menopausal status (25.4%) and BMI (11). At the same study, operator experience, whether performed by resident physician in training or by specialist in gynecology, was not associated with specimen adequacy. Although collection of all samples in this study by a single gynecologic oncologist was an advantage, limited number of patients could be considered as a disadvantage.

In endometrial sampling, both the diagnosis and exclusion of malignancy are important tasks. In this study, specimen inadequacy was not encountered whether specimens were obtained by Pipelle^® biopsy or D&C in cases with endometrial hyperplasia or endometrial carcinoma. Regarding pathology results, diagnostic consistency of the two methods was 100% (Table 3). Amant et al. (12) reported that malignancy diagnosis was ruled out in 96% by using the postmenopausal endometrial thickness >4 mm as cut-off value.

Table 3

However, in exclusion of malignancy, regularity of the entire endometrial cavity is an important factor. In 3 of our endometrial carcinoma cases, endometrial irregularities were noticed as invasions into the myometrium. In this study, we diagnosed 3 endometrial cancers, these cases had >7 mm endometrial thickness. Behnamfar and Arshad (13) reported the sensitivity and specificity of Pipelle^® biopsy as 94.1% and 100%, respectively. The one leiomyosarcoma case was diagnosed only with D&C method.

In a cohort of 1,535 cases, Machado et al. (14) Pipelle^® biopsy’s sensitivity and specificity in atypic hyperplasia and endometrial carcinoma diagnoses were reported as 84% and 99%, respectively. In another study, diagnostic accuracy for high grade endometrial cancer was higher than that of low-grade endometrial cancer by Pipelle^® biopsy (15). Antoni et al. (16) observed 71% sensitivity and 60% specificity in endometrial hyperplasia and endometrial cancer diagnoses. The latter percentages are lower than our findings. However, there was not any atypical hyperplasia case, which was a limitation in our study.

In this study of Pipelle^® and D&C comparison in biopsy, very consistent results were observed except for endometrial polyp diagnosis. In detail, 13 inconsistent cases out of 14 (92.8%) had endometrial polyps (Table 4).

Table 4

In their study, while Xie et al. (17) were able to diagnose all of the endometrial cancer cases by Pipelle^® biopsy, the most common reasons for inconsistent results were endometrial polyp and atypical hyperplasia diagnoses. In diagnosing atypical hyperplasia and endometrial polyps, they reported the sensitivity and specificity of Pipelle^® biopsy as 50% and 26.4%, respectively (17).

In their study, Dijkhuijen et al. (18) reported that in cases with endometrial polyps and endometritis, the sensitivity was 60% for Pipelle^® biopsy and was 88.9% for D&C, with the accuracy rates of 98.6% and 99.3%, respectively. The possible reason for the relatively lower sensitivity of these two methods on certain diagnoses such as endometritis and polyps is inadequate sampling.

Chaudry and Javaid (19) observed high accuracy and consistency rates on histopathologic diagnosis results between Pipelle^® biopsy and D&C, and they found Pipelle^® biopsy method more advantageous since it is less invasive. However, Clark et al. (20), suggested that the Pipelle^® biopsy accuracy rates might be lower and therefore additional diagnostic procedures would be recommended in cases with ongoing symptoms.

Several complications can be encountered during an endometrial sampling procedure, uterine perforation is the most bothersome. Seamark (21) reported 1% perforation rate during D&C procedures. In a study of Piatek et al. (11), D&C related uterine perforation rate was 0.5% and no complication was observed during Pipelle^® biopsy procedures. In our current study, neither perforation nor other complications were occurred in either Pipelle^® biopsy or in D&C groups.

Study Limitations

Finally, we mentioned some limitations and strengths of this study. Collection of all samples by experienced gynecologic oncologist and analysis of all samples by the same gyneco-pathologist were the strengths of the study, while presence of a single pathologist in analyzing process, absence of hysterectomy specimens as a definitive pathology results and low number of patients were among its limitations.

Conclusion

In this study, final pathology results were highly correlated between Pipelle^® biopsy and D&C procedures. Pipelle^®biopsy has lower complication rates, it is less painful and it does not require anesthesia. It can be reliably preferred over D&C in the diagnosis of endometrial pathologies with its comparable consistency rates. Future prospectively designed and larger studies would contribute more on this important subject.

Ethics

Ethics Committee Approval: Namık Kemal University Faculty of Medicine Clinical Research Ethical Board approval was obtained (document number 2020.87.04.11, April 30^th, 2020).

Informed Consent: This study were designed as hospital data research retrospectively.

Peer-review: Externally peer-reviewed.

Financial Disclosure: The author declared that this study received no financial support.

References

Cameron ST, Walker J, Chambers S, Critchley H. Comparison of transvaginal ultrasound, saline infusion sonography and hysteroscopy to investigate postmenopausal bleeding and unscheduled bleeding on HRT. Aust N Z J Obstet Gynaecol 2001;41(3):291-294.

Gimpelson RJ, Rappold HO. A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage. A review of 276 cases. Am J Obstet Gynecol 1988;158(3 Pt 1):489-492.

McMenamin M, Lysakova-Devine T, Wingfield M, O’Herlihy C, O’Farrelly C. Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells. Reprod Biomed Online 2012;25(3):322-328.

Williams AR, Brechin S, Porter AJ, Warner P, Critchley HO. Factors affecting adequacy of Pipelle and Tao Brush endometrial sampling. BJOG 2008;115(8):1028-1036.

Yi Y, Bryce CL, Adambekov S, Edwards RP, Goughnour SL, Linkov F. Cost-effectiveness analysis of biopsy strategies for endometrial cancer diagnosis in women with postmenopausal bleeding: Pipelle sampling curette versus dilatation & curettage. Gynecol Oncol 2018;150(1):112-118.

Demirkiran F, Yavuz E, Erenel H, Bese T, Arvas M, Sanioglu C. Which is the best technique for endometrial sampling? Aspiration (pipelle) versus dilatation and curettage (D&C). Arch Gynecol Obstet 2012;286(5):1277-1282.

Dacco’ MD, Moustafa M, Papoutsis D, Georgantzis D, Halmos G, Magos A. An audit of using the H Pipelle for endometrial sampling at outpatient hysteroscopy and literature review comparison with the Pipelle de Cornier. Eur J Obstet Gynecol Reprod Biol 2012;165(2):299-301.

Saadia A, Mubarik A, Zubair A, Jamal S, Zafar A. Diagnostic accuracy of endometrial curettage in endometrial pathology. J Ayub Med Coll Abbottabad 2011;23(1):129-131.

Kurosawa H, Ito K, Nikura H, Takano T, Nagase S, Utsunomiya H, et al. Hysteroscopic inspection and total curettage are insufficient for discriminating endometrial cancer from atypical endometrial hyperplasia. Tohoku J Exp Med 2012;228(4):365-370.

Polena V, Mergui JL, Zerat L, Sananes S. The role of Pipelle Mark II sampling in endometrial disease diagnosis. Eur J Obstet Gynecol Reprod Biol 2007;134(2):233-237.

Piatek S, Warzecha D, Kisielewski F, Szymusik I, Panek G, Wielgos M. Pipelle biopsy and dilatation and curettage in clinical practice: are factors affecting their effectiveness the same? J Obstet Gynaecol Res 2019;45(3):645-651.

Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet 2005;366(9484):491-505.

Behnamfar F, Arshad E. Diagnostic values of pipelle and standard curettage compared to hysterectomy pathology in postmenopausal bleeding: a comparative study. Adv Biomed Res 2020;9:58.

Machado F, Moreno J, Carazo M, León J, Fiol G, Serna R. Accuracy of endometrial biopsy with the Cornier pipelle for diagnosis of endometrial cancer and atypical hyperplasia. Eur J Gynaecol Oncol 2003;24(3-4):279-281.

Huang GS, Gebb JS, Einstein MH, Shahabi S, Novetsky AP, Goldberg GL. Accuracy of preoperative endometrial sampling for the detection of high-grade endometrial tumors. Am J Obstet Gynecol 2007;196(3):243.e1-5.

Antoni J, Folch E, Costa J, Foradada CM, Cayuela E, Combalia N, et al. Comparison of cytospat and Pipelle® endometrial biopsy instruments. Eur J Obstet Gynecol Reprod Biol 1997;72(1):57-61.

Xie B, Qian C, Yang B, Ning C, Yao X, Du Y, et al. Risk factors for unsuccessful office-based endometrial biopsy: a comparative study of office-based endometrial biopsy (Pipelle®) and diagnostic dilation and curettage. J Minim Invasive Gynecol 2018;25(4):724-729.

Dijkhuizen FP, Mol BW, Brölmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000;89(8):1765-1772.

Chaudry A, Javaid M. Clinical usefulness of Pipelle® endometrial sampling. Pak Armed Forces Med J 2005;55(2):122-125.

Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial hyperplasia. Acta Obstet Gynecol Scand 2001;80(9):784-793.

Seamark CJ. The demise of the D&C. J R Soc Med 1998;91(2):76-79.

Factors Affecting the Diagnostic Accuracy of Endometrial Pipelle® Biopsy