Interpretation of "Rare Goblet Cells Noted in a Background of Pseudo Goblet Cells" in Esophageal Biopsy
The finding of "rare goblet cells noted in a background of pseudo goblet cells" on an esophageal biopsy indicates early or limited intestinal metaplasia consistent with Barrett's esophagus, though this represents a borderline diagnostic finding that warrants careful interpretation and may require special stains for confirmation.
Understanding Goblet Cells vs. Pseudo Goblet Cells
True Goblet Cells:
- True intestinal-type goblet cells (ITGCs) are the hallmark of intestinal metaplasia and essential for diagnosing Barrett's esophagus
- They contain acid mucins that stain intensely blue with Alcian blue stain
- Their presence is required for a definitive diagnosis of Barrett's esophagus according to guidelines 1
Pseudo Goblet Cells:
- These are distended foveolar-type cells that can mimic true goblet cells
- They stain positive with PAS (Periodic Acid-Schiff) but do not contain acid mucins
- They do not stain with Alcian blue at pH 2.5
- They represent a potential diagnostic pitfall that can lead to overdiagnosis of Barrett's esophagus 1
Clinical Significance
Diagnostic Implications:
- The presence of even rare true goblet cells is sufficient for a diagnosis of Barrett's esophagus if found in the appropriate endoscopic context
- According to the AGA Chicago Workshop, intestinal metaplasia documented by histology is a prerequisite criterion for diagnosing Barrett's esophagus 1
- The British Society of Gastroenterology guidelines state that intestinal metaplasia is most biologically unstable with the greatest risk of neoplastic progression 1
Risk Assessment:
- Research shows that only the presence of true intestinal-type goblet cells is associated with a significant risk for dysplasia (p = 0.008) 2
- Goblet cell mimickers (pseudo goblet cells) are not associated with an increased risk for dysplasia 2
- The annual incidence of high-grade dysplasia and cancer in patients with intestinal metaplasia is significantly higher than in those without (0.38% vs 0.07%) 1
Diagnostic Approach
Confirmation of True Goblet Cells:
- In cases where goblet cells are rare or when prominent pseudo goblet cells are present, special stains can help confirm the diagnosis 1
- Alcian blue/PAS stain is recommended to differentiate true goblet cells from pseudo goblet cells
- True goblet cells will stain intensely blue with Alcian blue due to acid mucins
- Pseudo goblet cells will stain with PAS but not with Alcian blue 1
Sampling Considerations:
- When goblet cells are rare, deeper sections may be necessary
- Research shows that 4 levels of step sections are generally adequate for demonstrating goblet cell metaplasia 3
- For patients with suspected or known Barrett's esophagus, deeper sections may be warranted to find additional foci of goblet cell metaplasia 3
Recommendations for Follow-up
- Confirm the presence of true goblet cells using Alcian blue/PAS stain if not already done
- Ensure proper endoscopic documentation using Prague criteria (C, M) to establish the extent of columnar-lined esophagus 1
- If true goblet cells are confirmed, follow standard Barrett's esophagus surveillance protocols
- If only pseudo goblet cells are present without true goblet cells, the diagnosis of Barrett's esophagus should not be rendered 2
Pitfalls to Avoid
- Overdiagnosis of Barrett's esophagus based solely on pseudo goblet cells (occurs in up to 38% of cases by general pathologists) 1
- Relying on routine H&E staining alone when goblet cells are rare or when pseudo goblet cells are prominent
- Inadequate sampling (the Seattle biopsy protocol with four-quadrant biopsies every 2 cm is recommended) 1
- Failure to correlate histological findings with endoscopic appearance
Remember that the definitive diagnosis of Barrett's esophagus requires both endoscopic evidence of columnar metaplasia in the esophagus and histologic confirmation of intestinal metaplasia with true goblet cells.