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Related Experiment Video

Updated: Jan 3, 2026

Diagnosis of Hirschsprung's Disease by Immunostaining Rectal Suction Biopsies for Calretinin, S100 Protein and Protein Gene Product 9.5

Diagnosis of Hirschsprung's Disease by Immunostaining Rectal Suction Biopsies for Calretinin, S100 Protein and Protein Gene Product 9.5

Published on: April 26, 2019

Are We Underdiagnosing Hirschsprung Disease?

Raj P Kapur¹, Lusine Ambartsumyan², Caitlin Smith³

¹Department of Pathology, Seattle Children's Hospital and the University of Washington, Seattle, Washington.

Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society

|November 22, 2019

Summary

Hirschsprung disease (HSCR) diagnosis may miss milder cases due to new biopsy methods. Submucosal nerve changes and cholinergic innervation are key in identifying these subtle HSCR presentations.

Keywords:

Hirschsprung biopsy calretinin diagnosis false-negative nerve hypertrophy transition zone

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Area of Science:

Gastroenterology
Pediatric Surgery
Pathology

Background:

Hirschsprung disease (HSCR) is characterized by aganglionosis in the distal bowel.
Recent research highlights HSCR's variable expressivity and genetic complexities.
Understanding the full spectrum of HSCR pathology is crucial for accurate diagnosis.

Purpose of the Study:

To re-evaluate diagnostic criteria for Hirschsprung disease.
To emphasize the importance of submucosal nerve and cholinergic innervation assessment.
To address potential diagnostic limitations in milder HSCR cases.

Main Methods:

Review of conventional HSCR pathology definitions.
Analysis of recent findings in HSCR pathology and genetics.
Evaluation of diagnostic utility of rectal biopsies, including immunohistochemistry.

Main Results:

Standard rectal biopsies may miss HSCR in patients with short-segment or atypical pathology.
Submucosal nerve hypertrophy and abnormal cholinergic innervation can be critical diagnostic indicators.
Current reliance on calretinin immunohistochemistry may overlook subtle HSCR manifestations.

Conclusions:

The diagnostic approach to HSCR requires reassessment to include milder phenotypes.
Accurate identification of all HSCR cases is vital for patient management and genetic counseling.
Pathological assessment should encompass submucosal and mucosal innervation patterns.