What is the incidence of false negative Esophagogastroduodenoscopy (EGD) biopsies?

Incidence of False Negative EGD Biopsy

The incidence of false negative Esophagogastroduodenoscopy (EGD) biopsies ranges from 2-14%, with histopathological interpretation being the most substantial cause of false-negative results. 1, 2, 3

Factors Affecting False Negative Rates

Endoscopist Factors

• Endoscopist biopsy rate (EBR) significantly impacts diagnostic accuracy, with higher EBR (≥43.8%) associated with better detection of gastric premalignant conditions and lower risk of missed gastric cancers 4
• Inadequate mucosal visualization due to poor technique or preparation can lead to missed lesions 5
• Sampling from inappropriate sites is a major radiological cause of false-negative results 1
• Failure to follow standardized biopsy protocols for specific conditions increases risk of missed diagnoses 5

Pathological Factors

• Histopathological non-homogeneity of cancer infiltration can lead to false-negative results 1
• Interpretation errors account for approximately 64% of false-negative diagnoses 1
• The reproducibility of cytopathological diagnosis varies based on the pathologist's experience with EUS-guided biopsies 2

Reducing False Negative Rates

Standardized Biopsy Protocols

• For suspected malignant lesions, a minimum of six representative biopsies should be taken 6, 5
• For Barrett's esophagus, biopsies should follow the Seattle protocol (quadrantic biopsies at 2 cm intervals) 6, 5
• For gastric atrophy or intestinal metaplasia, separate biopsies from the gastric antrum and body should be taken 6
• For suspected celiac disease, a minimum of four biopsies should be taken, including specimens from the second part of the duodenum and at least one from the duodenal bulb 6

Quality Improvement Measures

• Endoscopists should perform a minimum of 100 OGDs per year to maintain competence 6, 5
• Photo-documentation of relevant anatomical landmarks and any detected lesions is essential 6
• When biopsies are obtained from normal-appearing gastric body and antrum for H. pylori detection, the 5-biopsy updated Sydney protocol (specimens from antrum, incisura, and body) improves diagnostic yield 6
• Gastric ulcers should be biopsied and re-evaluated after appropriate treatment within 6-8 weeks 6

Expert Review

• All dysplasia should be confirmed by an experienced GI pathologist, as approximately 40% of cases initially classified as "indefinite for dysplasia" may be reclassified upon expert review 6
• In case of radiological-histopathological divergence, histopathological analysis of biopsy specimens should be repeated 1
• Patients with indefinite or low-grade dysplasia who are infected with H. pylori should be treated and have eradication confirmed, followed by repeat endoscopy and biopsies 6

Special Considerations

High-Risk Lesions

• For suspected high-grade dysplasia (HGD) or early gastric cancer, endoscopic submucosal dissection (ESD) with en bloc, R0 resection is recommended for accurate pathologic staging 6
• After ESD or endoscopic mucosal resection (EMR) of neoplasia, follow-up endoscopy should be performed at 6 months, and if no lesions are identified, annually thereafter 6
• For visible dysplasia, endoscopic resection is preferred over surveillance when appropriate 6

Monitoring Quality

• Endoscopy units should audit rates of failing to diagnose cancer at endoscopy up to 3 years before an esophagogastric cancer is diagnosed 6, 5
• A method for ensuring histological results are processed must be in place 6
• After OGD, readmission, mortality, and complications should be audited 6

By implementing these standardized approaches to biopsy technique, specimen handling, and pathological review, the incidence of false negative EGD biopsies can be minimized, leading to improved patient outcomes through earlier detection and treatment of significant pathology.