Practical pathology and genetics of Hirschsprung's disease

Diagnosis and management of Hirschsprung's disease (HSCR) requires understanding of the malformation's anatomic features and multigenic nature. Rectal biopsies, intraoperative frozen sections, and resection specimens provide invaluable information. Extraction of these data requires thoughtful biopsy technique, adequate histologic sections, histochemistry, and collaboration of surgeon and pathologist. Critical consideration of transition zone anatomy and published studies of “transition zone pull through” indicate that more research is needed to determine how much ganglionic bowel should be resected from HSCR patients. Many HSCR-susceptibility genes have been identified, but mutational analysis has limited practical value unless family history or clinical findings suggest syndromic HSCR.