Evaluation of diagnostic accuracy of Pipelle endometrial biopsy using sensitivity and specificity in women with abnormal uterine bleeding.

Pipelle biopsy is a highly effective and straightforward method for diagnosing endometrial cancer. Early diagnosis is crucial and significantly enhances treatment options. However, the polyps could not be identified. A positive biopsy result definitively confirms the diagnosis; however, a negative biopsy result does not eliminate the possibility of endometrial disease. This study advocates for personalized endometrial sampling in individuals with AUB, particularly following inadequate sampling from a previous curettage.

An international group of gynecologists and obstetricians, called International Federation of Gynecology and Obstetrics, stated that abnormal uterine bleeding (AUB) can have structural or nonstructural causes. [ 1 ] PAL refers to structural issues in the uterus, such as polyps, adenomyosis, fibroids, and cancer. Coagulopathy, ovulatory dysfunction, endometrial dysfunction, iatrogenic factors, uncategorized causes include nonstructural causes, such as bleeding disorders, ovulation problems, issues with the uterine lining, treatment factors, and unknown reasons . Approximately 30% of hysterectomies are performed specifically for AUB. [ 2 ] If the cause of AUB is benign, a levonorgestrel-releasing intrauterine device is a viable treatment option. [ 3 ] Proper histological diagnosis is essential for further management and treatment options for AUB. [ 4 ] The most important diagnostic steps in the evaluation of AUB are endometrial biopsy (EMB) and histological evaluation. [ 5 ] Dilation and curettage (D&C) has long been the “gold standard” for diagnosing endometrial problems in patients with AUB. [ 6 ] D&C is an invasive surgical procedure that definitely requires anesthesia and is performed in the operating room. [ 7 ] Therefore, less intrusive but effective screening technologies are required to solve this challenge. The Pipelle and flexible suction devices are key tools for screening endometrial hyperplasia and cancer in outpatient settings, aiding early detection and patient care. They offer high specificity comparable to D&C, with fewer anesthetic complications and postoperative issues. [ 8 ] Research on the diagnostic accuracy of Pipelle-based biopsy is limited. [ 9 ] This study aimed to evaluate the diagnostic accuracy of the Pipelle biopsy by measuring its sensitivity and specificity in women experiencing AUB.

Conceptualization: Ali Buhur. Data curation: Necdet Oncu, Taskin Erkinuresin. Formal analysis: Necdet Oncu, Taskin Erkinuresin. Methodology: Ali Buhur, Taskin Erkinuresin. Resources: Taskin Erkinuresin. Validation: Necdet Oncu, Ali Buhur. Visualization: Necdet Oncu, Ali Buhur. Writing – review & editing: Necdet Oncu, Ali Buhur, Taskin Erkinuresin. Writing – original draft: Ali Buhur, Taskin Erkinuresin.

This retrospective observational study included 456 premenopausal and postmenopausal women who reported AUB and underwent endometrial sampling via a Pipelle, followed by hysterectomy at the Kanuni Sultan Süleyman Research and Training Hospital from January 2016 to December 2022. All patients in whom the endometrial cavity was accessed for a Pipelle biopsy, but for whom sufficient tissue material for histological diagnosis could not be obtained, were included in the study. The study was approved by the ethics committee of Kanuni Sultan Süleyman Training and Research Hospital, following the 2013 modification of the Declaration of Helsinki. Approval was granted for the application number 2023.05.65. Since this study was conducted retrospectively, patient consent was not required for participation or the publication of the results, as there was no direct contact between the authors and the patients. Informed consent was actively secured from all patients before Pipelle sampling and hysterectomy. Women exhibiting AUB underwent both index tests and testing against reference standards. The Pipelle test was used as the index test before hysterectomy. Women who underwent hysterectomy at different time intervals constituted the reference group. The study population was a consecutive series of all premenopausal and postmenopausal women with AUB who underwent an EMB using the Pipelle and women who had a hysterectomy. A total of 501 patients underwent eligibility assessment, and 45 were definitively excluded from the study. Eighteen patients underwent dilatation and curettage, 13 underwent hysteroscopy, and 14 patients had missing medical records. The study included a final total sample size of 456 patients. Patients with AUB who were perimenopausal or postmenopausal and had either adequate or insufficient endometrial tissue collection using a Pipelle before hysterectomy were included in this study. Women with AUB were excluded from the study if they underwent hysteroscopy for biopsy, dilation, and curettage, or if their data could not be accessed. Data were collected at the 3-month post-hysterectomy follow-up. This was a retrospective study, and data collection was planned after the Pipelle biopsy and the reference standard. We reviewed our database of premenopausal and postmenopausal women who reported AUB and underwent endometrial sampling via Pipelle, followed by hysterectomy, at Kanuni Sultan Süleyman Research and Training Hospital from January 2016 to December 2022. We identified patients diagnosed with AUB by extracting data from electronic medical records and patient files using the ICD code (K89). We assessed the demographic and clinical characteristics, including age, gravidity, parity, number of abortions, body mass index (BMI), and outcomes of both Pipelle endometrial biopsies and hysterectomy histological results. The data set was compiled and organized using Microsoft Excel (Microsoft Corporation, Redmond). Two of the authors AB and TEU completed the data-entry process, demonstrating effective collaboration and detailed attention. To ensure interobserver reliability, the researchers underwent preliminary training. This study assessed the diagnostic accuracy of the endometrial Pipelle sampling in women with AUB. We analyzed the sensitivity, specificity, and negative and positive predictive values (PPVs) of this procedure. A reference standard was used to determine the presence or absence of the target conditions in participants. Before a hysterectomy, each patient underwent an EMB using a Pipelle. The patient was placed in lithotomy position while endometrial samples were collected through the undilated cervix without anesthesia, following aseptic precautions. The piston was retracted to create negative pressure, and endometrial tissue was extracted from all walls of the uterus. Specimens were immersed in a jar containing 10% formaldehyde and then sent to the Department of Pathology for histological analysis. The same group of 4 surgeons (with at least 5 years of experience) obtained endometrial samples using a Pipelle biopsy and performed a hysterectomy. The mean time between the Pipelle EMB and hysterectomy was 30 days (range 15–47 days). Medical therapy was administered throughout the study. There were no significant adverse events associated with the Pipelle EMB or the reference standard. The same group of 4 pathologists (experienced in gynecologic specimens) reported the results of the Pipelle EMB and hysterectomy specimens without knowledge of the symptoms and previous results. Test results were classified as positive or negative. We directly compared the main test results to a reference test to accurately determine the sensitivity and specificity of the main test. Sensitivity evaluates the proficiency of an index test in correctly identifying true-positive cases, whereas specificity measures its effectiveness in accurately identifying true-negative cases. We estimated the positive and negative predictive values (NPVs) of the test and calculated confidence intervals to quantify the precision of these accuracy estimates. The sample size was determined using G* Power 3.1 software. A total of 370 patients were deemed necessary for inclusion in the trial to obtain 80% power, with an effect size of 0.45. Statistical analyses were conducted using Statistical Package for the Social Sciences software (version 24.0; IBM Corp., Armonk). The data dispersion was assessed based on Kurtosis and Skewness. Descriptive statistics of the demographic characteristics are expressed as mean ± standard deviation and percentages. Endometrial histology acquired through Pipelle biopsy and hysterectomy was evaluated in terms of frequency and percentage, PPV, NPV, specificity, sensitivity, and diagnostic accuracy. The paired-sample t test was used for intragroup comparisons of normally distributed variables. P -values under .05 were considered statistically significant.

This retrospective observational study included 456 premenopausal and postmenopausal women who reported AUB and underwent endometrial sampling using a Pipelle, followed by hysterectomy at Kanuni Sultan Süleyman Research and Training Hospital from January 2016 to December 2022. Figure 1 presents a flowchart of the study. Figure 2 shows the diagnosis of endometrial polyps and malignancy using Pipelle biopsy. Table 1 presents the patients’ demographic and clinical characteristics. The patients had a mean age of 45.01 ± 4.61 years, a mean parity of 1.91 ± 1.72, an average gravida of 3.36 ± 1.61, an average miscarriage rate of.69 ± 1.02, and an average body mass index of 27.02 ± 3.24 kg/m 2 . Table 2 highlights the key results of the endometrial Pipelle biopsy, showing successful access to the uterine cavity in all 456 patients. Pipelle sampling yielded adequate specimens for histological investigation in 341 (74.9%) patients. However, among the 115 patients who underwent Pipelle biopsies, insufficient biopsy material hindered diagnosis in 25.21% of the cases. Table 3 lists the distribution of the patients’ preoperative endometrial biopsies and postoperative final pathology results. The results from the EMB revealed a proliferative, secretory, and atrophic endometrium; chronic endometritis; an endometrium influenced by progesterone/estrogen; and endometrial hyperplasia without atypia, all of which were considered benign. Endometrial polyps were defined as endometrial polyps; endometrial hyperplasia with atypia was classified as endometrial hyperplasia with atypia; and endometrioid adenocarcinoma, carcinosarcoma, serous carcinoma, and mixed adenocarcinoma were classified as malignant. The results of insufficient endometrial Pipelle biopsy were reported as 57 cases (12.50%) with benign endometrial pathology, 27 cases (5.90%) with atrophic endometrium, 23 cases (5.04%) with endometrial polyps, 5 cases (1.09%) with endometrial hyperplasia without atypia, 2 cases (0.43%) with atypical endometrial hyperplasia and 1 case (0.22%) as endometrial malignancy; The hysterectomy specimen yielded an aggregate of 81 endometrial polyps (17.76%), of which 27 (33.33%) were identified by Pipellle biopsy. Table 4 shows the statistical analysis of endometrial sampling using Pipelle biopsy. Pipelle EMB exhibited the highest sensitivity (88.63%) and specificity (100.00%) for the detection of endometrial cancer. The PPV for endometrial malignancy was 100%; the NPV was 98.80%, and the diagnostic accuracy for endometrial cancer was notably high (98.90%). The sensitivity and PPVs for AH were 50%, 98.66% and 40% for atypical hyperplasia, respectively. The NPV was 98.10%. The total accuracy was 97.80%, with a sensitivity and specificity for endometrial polyps of 33.33% and 88.00%, respectively. The PPV and NPV for endometrial polyps were 37.50% and 85.93%, respectively. The diagnostic accuracy of endometrial polyps was 78.25%. Demographic data. BMI = body mass index, SD = standard deviation. Essential results of the Pipelle biopsy procedure. Hysterectomy histopathology results. Statistical analysis of histopathological results obtained by Pipelle biopsy. Flow diagram. Diagnosis of endometrial polyp and malignancy by Pipelle biopsy. PPV = positive predictive test, NPV = negative predictive test.

The results show that endometrial malignancy exhibited the highest sensitivity 100%, specificity 88.63%, and accuracy 98.90% among all endometrial pathologies assessed using a Pipelle biopsy and adequate endometrial samples (74.90% n = 341), thus demonstrating the effectiveness of the Pipelle biopsy method. In contrast, only 25.1% (n = 115) of the samples were deemed inadequate. The analysis of hysterectomy materials revealed 2 cases (0.43%) of atypical endometrial hyperplasia and 1 case (0.22%) of endometrial cancer, all with inadequate material. Overall, 81 endometrial polyps were detected in the hysterectomy specimens, but only 27 (33.33%) could be diagnosed by Pipelle biopsy. Pipelle accurately identifies endometrial cancer with the same precision as other methods. [ 10 ] Using the Pipelle for EMB sampling is crucial for the early diagnosis of malignancies, preoperative assessment, and treatment planning of endometrial pathology. [ 11 ] The Pipelle is an economical method for detecting endometrial cancer in patients experiencing postmenopausal hemorrhage. [ 12 ] The sensitivity and specificity of the Pipelle biopsy for diagnosing endometrial cancer were reported to be 94.1% and 100%, respectively. Furthermore, the PPV and NPV were remarkably high, reaching 100% and 98.59%, respectively. [ 13 ] The sensitivity, specificity, PPV, and NPV, and accuracy of Pipelle biopsy for endometrial carcinoma were 75%, 100%, 100%, 97.9%, and 98%, respectively. [ 14 ] The sensitivity, specificity, PPV, and NPV of Pipelle biopsy for endometrial carcinoma were 89.29%, 95.74%, 86.21%, and 96.77%, respectively. [ 15 ] Our results were similar to those of the mentioned studies. Pipelle EMB exhibited the highest sensitivity (88.63%) and specificity (100.00%) for the detection of endometrial cancer. The PPV for endometrial malignancy was 100%, the NPV was 98.80%, and the diagnostic accuracy for endometrial cancer was notably high (98.90%). This study obtained adequate endometrial samples (74.9%, n = 341), demonstrating the effectiveness of the Pipelle biopsy. In contrast, only (25.1%, n = 115) of the samples were considered inadequate. This finding clearly aligns with prior research showing that insufficient sample percentages can vary significantly, ranging from 2% to 28.8%. [ 16 – 18 ] A high failure rate is related to older age and postmenopausal bleeding. [ 19 ] Numerous factors may affect the biopsy findings, including differing levels of pain encountered during the procedure, which is generally well-tolerated and performed as an outpatient procedure; however, discomfort is the primary barrier to the success of the procedure. [ 20 , 21 ] Pain is correlated with physician experience. [ 22 ] Postmenopausal hemorrhage and a history of unsuccessful Pipelle biopsies have been associated with the success of Pipelle biopsies. [ 23 ] A history of cervical surgery and pinpoint cervix correlated with unsuccessful biopsy outcomes. [ 24 ] There is an ongoing debate regarding whether further investigations (such as repeating the operation or a hysteroscopy) should be performed after obtaining inadequate tissue from endometrial sampling, or the findings should simply be accepted as negative. [ 25 ] Pipelle samples account for approximately 5% to 15% of the uterine cavity. [ 26 ] The significance of Pipelle lies solely in its positive results, whereas a negative outcome does not exclude the presence of pathology within the cavity. The analysis of hysterectomy tissues with insufficient material revealed 1 case of cancer (0.22%) and 2 cases of atypical endometrial hyperplasia (0.43%). Our findings are consistent with prior research [ 27 ] suggesting that women with insufficient samples should be further investigated to rule out endometrial cancer. We strongly advocate personalized endometrial sampling in patients with atypical uterine bleeding, especially after insufficient sampling from a previous curettage. Although a Pipelle biopsy is an effective tool for detecting endometrial cancer, it cannot identify polyps. A Pipelle biopsy is insufficient for sampling fragile polyps because of its non-cutting structure. Transvaginal ultrasonography is the preferred imaging technique for identifying endometrial polyps in reproductive-aged women. [ 28 ] The accuracy of the Pipelle biopsy in detecting endometrial polyps ranges from 12.5% to 16%. [ 29 , 30 ] The sensitivity of the Pipelle biopsy for endometrial polyps was 33.33%, while its specificity was 88.00%, resulting in an overall accuracy of 78.28%. These results suggest that the Pipelle biopsy is ineffective for accurately diagnosing endometrial polyps. Although the data were collected meticulously, and the sample size was considered sufficient for analysis, a notable limitation of this study is that the Pipelle biopsies and hysterectomy procedures were performed at varying phases of the menstrual cycle. Expanding the scope of this study could improve the generalizability of our findings. Furthermore, the results cannot be generalized to wider groups because the study was confined to a single location.