What is distal esophagus squamous mucosa with basal cell hyperplasia, significant glycogenation, and focal intraepithelial lymphocytes concerning for?

Histologic Findings Concerning for Eosinophilic Esophagitis

The combination of distal esophagus squamous mucosa with basal cell hyperplasia, significant glycogenation, and focal intraepithelial lymphocytes is most concerning for eosinophilic esophagitis (EoE), though the diagnosis requires correlation with eosinophil counts and clinical symptoms.

Primary Diagnostic Consideration: Eosinophilic Esophagitis

The histologic features described are characteristic findings in EoE:

• Basal cell hyperplasia is one of the major histologic features of EoE, typically defined as basal zone occupying more than 20% of the epithelium 1, 2
• Intraepithelial lymphocytes are consistently increased in EoE biopsy specimens compared to reference groups, and are more abundant in pre-treatment specimens 1
• Glycogenation (spongiosis/intercellular edema) is a frequent minor feature of EoE 2

Critical Diagnostic Requirements

To confirm EoE, you must verify:

• Peak eosinophil count ≥15 eosinophils per 0.3 mm² (high-power field) in at least one biopsy specimen 1, 3
• Clinical symptoms of esophageal dysfunction (dysphagia, food impaction in adults; feeding problems, vomiting in children) 1, 3
• Exclusion of GERD through either normal pH monitoring or lack of response to high-dose PPI therapy 1

The pathology report should specifically document whether eosinophils meet this threshold, as the features you describe are supportive but not diagnostic without adequate eosinophil counts 1.

Additional Histologic Features to Assess

Request the pathologist to evaluate for:

• Eosinophil microabscesses (clusters of ≥4 eosinophils), which are found exclusively in EoE and not GERD 1
• Superficial layering of eosinophils in the upper one-third to one-half of squamous epithelium 1
• Eosinophil degranulation with extracellular major basic protein deposition 1
• Papillary lengthening and lamina propria fibrosis 1

These additional features significantly strengthen the diagnosis of EoE when present 1, 2.

Alternative Diagnostic Considerations

GERD-Related Esophagitis

While basal cell hyperplasia and papillary elongation occur in GERD, key distinguishing features include 1:

• GERD typically shows <10 eosinophils per high-power field 1
• Absence of eosinophil microabscesses and superficial layering 1
• Predominant involvement of distal esophagus only 2
• Response to high-dose PPI therapy 1

PPI-Responsive Esophageal Eosinophilia

This entity is histologically indistinguishable from EoE but responds to PPI therapy 1. The same histologic features (basal hyperplasia, lymphocytes, eosinophilia) are present in both conditions 1.

Squamous Dysplasia (Less Likely)

Basal cell hyperplasia can occur in dysplastic lesions 1, 4, but:

• Dysplasia would show cytologic atypia and loss of maturation not mentioned in your description 4, 5
• Glycogenation is not a typical feature of dysplasia 6
• This diagnosis requires specific architectural and cytologic abnormalities 5

Recommended Clinical Algorithm

Step 1: Review the complete pathology report

• Confirm peak eosinophil count per 0.3 mm² 1
• Document presence/absence of eosinophil microabscesses and superficial layering 1

Step 2: If eosinophils ≥15 per 0.3 mm²

• Assess for typical EoE symptoms (dysphagia, food impaction) 1, 3
• Evaluate for atopic conditions (50-80% of EoE patients have allergic rhinitis, asthma, or eczema) 3
• Consider trial of high-dose PPI therapy (twice daily) for 8-12 weeks to exclude PPI-responsive disease 1

Step 3: If eosinophils <15 per 0.3 mm²

• Consider GERD as primary diagnosis 1
• Initiate high-dose PPI therapy 1
• Repeat endoscopy with biopsies from both proximal and distal esophagus after 8-12 weeks of maximal acid suppression 1, 2

Step 4: Obtain biopsies from multiple sites

• EoE has patchy distribution and affects proximal esophagus equally or more than distal 2
• Minimum of 6 biopsies from at least 2 different esophageal sites are recommended 1
• Include both visibly abnormal and normal-appearing areas 1

Critical Pitfalls to Avoid

• Do not diagnose EoE based on histology alone without clinical correlation and eosinophil counts 1
• Do not biopsy during active erosive esophagitis (Los Angeles grade C/D), as inflammation can cause over-diagnosis; repeat after 8-12 weeks of high-dose PPI therapy 1
• Do not rely on distal esophagus biopsies alone, as EoE often preferentially affects proximal esophagus 2
• Do not assume absence of peripheral eosinophilia excludes EoE; only 10-50% of adults with EoE have elevated peripheral eosinophil counts 3