False-Negative Biopsies in Endometriosis

How a Biopsy Is Taken

During laparoscopic surgery (“keyhole surgery”), surgeons often take biopsies of areas that appear suspicious for endometriosis. These areas are identified based on visual characteristics that trained surgeons recognize.

To obtain a biopsy, the surgeon uses laparoscopic instruments—such as graspers and biopsy forceps—to hold and remove a small tissue sample. This typically involves cutting a small piece of tissue from the area of concern.

The sample is then sent to a laboratory, where a histopathologist examines it under a microscope. They assess the tissue for abnormalities and look for features that meet the diagnostic criteria for endometriosis.

However, false negatives can occur. While biopsies are reliable when they confirm endometriosis, they are not perfect at ruling it out. A negative result does not necessarily mean the disease is absent—it may simply have been missed in the sampled tissue.

1. Reported Prevalence Across Research

Several studies have evaluated how often biopsies fail to detect endometriosis:

• Chen et al. (135 patients)

  • Initial biopsies missed endometriosis in 8.3% of cases

  • Detection improved from 73.3% to 80% (+6.7%) when deeper tissue sections were analyzed

  • This highlights the importance of biopsy depth and technique

• Alvarez et al. (148 patients)

  • Diagnostic yield ranged from 59% to 91%

  • Detection improved with:

    • Multiple biopsy sites

    • Surgeons with endometriosis subspecialty training

  • Results varied depending on both surgical and pathology practices

• Anwar et al. (64 patients)

  • 53.13% had histologically confirmed endometriosis

  • 46.87% were not confirmed despite clinical suspicion

  • This demonstrates discordance between clinical findings and biopsy results

Biopsy results can vary widely depending on technique, sampling, and interpretation.

2. What Drives False Negatives?

Current research suggests several contributing factors:

• Sampling limitations
  Endometriosis lesions vary in size, depth, color, and appearance. If the sampled tissue does not contain diagnostic cells, results may appear negative.

• Number of biopsy sites
  Fewer or more superficial samples increase the likelihood of missing disease.

• Variation in expertise
  Outcomes may differ depending on:

  • Surgeon experience (especially endometriosis specialists)

  • Pathologist training in gynecologic pathology

These variables make histologic diagnosis more complex and help explain why false negatives occur.

3. Prevention and Clinical Implications

While limited research focuses specifically on reducing false negatives, available evidence suggests improved detection when:

• Deeper tissue sections are analyzed after an initial negative result

• Multiple biopsy sites are sampled

• Procedures and interpretations are performed by experienced specialists

Because of these limitations, biopsy results are typically interpreted alongside:

• Clinical symptoms

• Imaging findings

• Surgical observations

A negative biopsy alone may not be sufficient to rule out endometriosis.

False-negative biopsies in endometriosis are most often due to limitations in sampling and interpretation, not the absence of disease.

This creates a significant challenge in care. Patients may continue to experience symptoms and uncertainty even after surgery, and clinicians may not always achieve definitive confirmation despite strong clinical suspicion.

Endometriosis is a complex condition that often requires a multi-step diagnostic approach involving collaboration between clinicians, surgeons, and pathologists. Understanding the limitations of biopsy is essential to ensuring patients receive informed, comprehensive care.

References

1. Mettler L, et al. Accuracy of Laparoscopic Diagnosis of Endometriosis. JSLS. 2024.

2. Chen CV, et al. Diagnostic Utility of Deeper Level Tissue Sections. Int J Gynecol Pathol. 2024.

3. Anwar R, et al. Misdiagnosis Rate of Endometriosis. Sage Open Medicine. 2026.

4. Alvarez V, et al. Improving Diagnostic Yield in Peritoneal Endometriosis. Int J Gynecol Pathol. 2025.

5. Clement PB. The Pathology of Endometriosis. Adv Anat Pathol. 2007.