Microscale Endometrial Sampling Biopsy in Detecting Endometrial Cancer and Atypical Hyperplasia in a Population of 1551 Women: A Comparative Study with Hysteroscopic Endometrial Biopsy

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Microscale Endometrial Sampling Biopsy in Detecting Endometrial Cancer and Atypical Hyperplasia in a Population of 1551 Women: A Comparative Study with Hysteroscopic Endometrial Biopsy

Background

Endometrial cancer represents a significant global health burden, ranking among the most common malignancies of the female reproductive system. The American Cancer Society estimated 61,380 new cases and 10,920 deaths in the United States in 2017, while global data from 2018 reported 382,096 new cases and 89,929 deaths. In China, the incidence reached 63.4 per 100,000 women in 2015, with a mortality rate of 21.8 per 100,000. Early detection remains critical for improving patient outcomes, yet cost-effective screening strategies for high-risk populations remain underdeveloped. Traditional diagnostic methods like dilatation and curettage (D&C) and hysteroscopic biopsy are invasive, resource-intensive, and unsuitable for widespread screening. Microscale endometrial sampling (MES) biopsy has emerged as a minimally invasive alternative, but its diagnostic accuracy and clinical utility require further validation. This study evaluates the specimen adequacy, diagnostic performance, and cost-effectiveness of MES biopsy compared to hysteroscopic endometrial biopsy in 1,551 high-risk women.

Methods

Study Population

The study included 1,551 women at high risk for endometrial lesions who underwent hysteroscopic endometrial biopsy between November 2017 and August 2018. Inclusion criteria encompassed abnormal uterine bleeding, ultrasound findings of intrauterine abnormalities (endometrial thickness ≥5 mm in postmenopausal women), or follow-up evaluations after progesterone treatment for endometrial hyperplasia or cancer. Exclusion criteria included cervical cancer, acute pelvic infections, recent childbirth or abortion, or current use of a levonorgestrel intrauterine system.

Sampling Techniques

MES biopsy was performed using the SAP-1 device (Saipujiuzhou, Beijing, China), a 2.8-mm diameter instrument with a flexible sheath and a serrated loop designed to collect microscale endometrial tissue. The device was inserted into the uterine cavity without cervical dilation, rotated 360° to sample all quadrants, and withdrawn with the loop retracted to avoid contamination. Specimens were fixed and processed into microtissue blocks for histopathological analysis.

Hysteroscopic biopsies were conducted under direct visualization using Olympus hysteroscopes. Tissue samples were fixed in formalin, embedded in paraffin, and stained for histopathological evaluation. Both procedures were performed sequentially under intravenous anesthesia.

Specimen Adequacy and Diagnostic Criteria

Specimen adequacy for MES biopsy was determined by three criteria: (1) visible endometrial scratch marks at hysteroscopy, (2) presence of ≥5 glandular epithelial cells, and (3) definitive pathological classification. Inadequate samples lacked sufficient tissue for diagnosis or failed to sample the fundus or tubal ostia.

Diagnostic categories included endometrial cancer, atypical hyperplasia, benign endometrial changes (proliferative/secretory endometrium, hyperplasia without atypia, endometritis), and intrauterine lesions (polyps, submucosal fibroids). Two independent pathologists blinded to the study interpreted results.

Statistical Analysis

Data analysis utilized SPSS 22.0. Chi-square tests compared specimen adequacy rates across subgroups. Logistic regression identified factors influencing adequacy. Diagnostic agreement was assessed using Cohen’s kappa. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MES biopsy using hysteroscopic biopsy as the gold standard. Medical costs were compared based on procedural expenses in China.

Results

Specimen Adequacy

Among 1,551 patients, MES biopsy achieved 81.2% specimen adequacy (1,260/1,551). Adequacy rates varied significantly:

  • Premenopausal vs. postmenopausal women: 89.6% (1,000/1,116) vs. 59.8% (260/435), P<0.001.
  • Malignant vs. benign lesions: 97.1% (166/171) vs. 79.3% (1,094/1,380), P<0.001.

Multivariate analysis identified key predictors:

  • Postmenopausal status increased inadequacy risk 3.16-fold (P<0.001).
  • Endometrial thickness <6.5 mm reduced adequacy (AUC=0.722, sensitivity=71.4%, specificity=66.7%).
  • Intrauterine lesions (polyps, fibroids) had a 30.95-fold higher inadequacy risk compared to endometrial cancer (P<0.001).

Diagnostic Performance

Consistency with Hysteroscopy

MES biopsy demonstrated excellent agreement with hysteroscopy for distinguishing malignant (cancer/atypical hyperplasia) from benign lesions (kappa=0.950, 95% CI: 0.925–0.975). For specific diagnoses:

  • Endometrial cancer: Sensitivity=91.7% (111/121), specificity=100%, PPV=100%, NPV=99.3% (1,430/1,440).
  • Atypical hyperplasia: Sensitivity=82.0% (41/50), specificity=100%, PPV=100%, NPV=99.4% (1,501/1,510).

Limitations in Diagnosing Intrauterine Lesions

MES biopsy showed poor concordance for intrauterine polyps or fibroids (kappa=0.248), attributed to insufficient sampling of stromal or fibrotic tissue.

Cost Comparison

The total medical cost for MES biopsy was 44.49 USD, including the SAP-1 device (24.22 USD), sampling procedure (5.47 USD), and pathology (14.79 USD). Hysteroscopic biopsy costs totaled 201.34 USD, covering hysteroscopy (170.13 USD), D&C (16.42 USD), and pathology. MES biopsy was 22.1% the cost of hysteroscopy.

Discussion

Clinical Implications of Specimen Adequacy

The 81.2% adequacy rate aligns with prior studies but highlights limitations in postmenopausal women and those with thin endometria. The SAP-1 device’s serrated loop improves tissue yield compared to suction-based devices, particularly in malignant lesions where friable tissue facilitates sampling. However, fibrotic or polypoid lesions remain challenging, necessitating hysteroscopy for definitive diagnosis.

Diagnostic Accuracy and Screening Utility

MES biopsy’s high sensitivity (91.7%) and specificity (100%) for cancer support its role as a first-line screening tool. The 82.0% sensitivity for atypical hyperplasia, while lower, remains clinically valuable given its cost-effectiveness. False negatives may arise from focal lesions or sampling errors, underscoring the need for hysteroscopy in high-risk cases with negative MES results.

Cost-Effectiveness and Accessibility

The 78% cost reduction compared to hysteroscopy positions MES biopsy as a pragmatic option for low-resource settings. Outpatient applicability further enhances accessibility, reducing hospitalization requirements.

Conclusion

Microscale endometrial sampling biopsy using the SAP-1 device is a minimally invasive, cost-effective method for endometrial cancer and atypical hyperplasia screening. Its high diagnostic accuracy for malignant lesions, combined with low cost and outpatient feasibility, supports integration into risk-stratified screening protocols. Hysteroscopy remains essential for inconclusive cases, intrauterine lesions, and postmenopausal women with inadequate samples. Future studies should explore MES biopsy in longitudinal screening programs to validate its long-term impact on endometrial cancer mortality.

doi.org/10.1097/CM9.0000000000001109

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