Aganglionosis and related disorders

Abstract

Congenital aganglionosis or Hirschsprung's disease (HD) characteristically presents with involvement of the sigmoid colon and rectum. There is an associated increase in cholinergic and adrenergic innervation in the affected bowel wall. Diagnosis of HD in the neonatal period is readily achieved via submucosal rectal biopsy with recognition of the immaturity of ganglion cells within the first year of life, use of a standardized protocol, and supplemental acetylcholinesterase stain. Morbidity and mortality from HD occur caused by Hirschsprung's-associated enterocolitis (HAEC); the pathologist can alert the clinician to the presence of HAEC. The HD variant to be aware of is total colonic aganglionosis, which may lack hypertrophic nerves and increased cholinergic nerve endings and contain zonal areas of some ganglion cells. Pseudo HD includes intestinal neuronal dysplasia (IND), chronic idiopathic intestinal pseudo obstruction (CIIP), and chronic constipation in children. Intestinal neuronal dysplasia is characterized by hyperganglionosis, whereas CIIP and chronic constipation in children share a common, newly described myopathic pathology. In this review investigation into peptidergic (VIPergic) innervation in pseudo HD and HD shows increased VIPergic immunostaining in CIIP, chronic constipation, and the ganglionic portion of HD; however, the VIPergic pattern is not diagnostically selective. Until the advent of new molecular biological techniques, histopathology remains the diagnostic gold standard in HD.