Colon nontumor
Congenital anomalies
Hirschsprung disease




Topic Completed: 1 May 2013

Revised: 7 January 2019, last major update May 2013

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Hirschsprung disease[title]
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Cite this page: Gulwani H. Hirschsprung disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/colonhirschsprung.html. Accessed April 23rd, 2019.
Definition / general
  • Caused by lack of parasympathetic ganglion cells in submucosal and myenteric plexus of part of colon, causing functional obstruction and colonic dilation proximal to affected segment (eMedicine)
Terminology
  • Also called congenital aganglionic megacolon
  • Classic: aganglionic portion begins in distal colorectum and extends a considerable distance proximally
  • Ultrashort segment: less than 2 cm affected in rectum and sigmoid; more common in boys; difficult to document because this portion of rectum typically lacks ganglion cells even in normals
  • Short segment: aganglionic portion involves rectum and rectosigmoid for only a few centimeters (Ann Saudi Med 2006;26:200)
  • Long segment: 10% of cases; involves 40 cm or more of colon, may extend into small bowel; patients have obstruction without megacolon; more common in girls; may lack hypertrophied nerve trunks, but do have increase in acetylcholinesterase+ nerve abnormalities
  • Zonal colonic aganglionosis: involvement of short segment of bowel; ganglion cells are present above and below this segment
  • Total colonic aganglionosis (TCA): uncommon; clinical, histologic, and genetic differences; more difficult to diagnose and manage (Arch Pathol Lab Med 2010;134:1467)
Pathophysiology
Clinical features
  • 80% male; usually sporadic (1 per 5,000 live births); occurs in 4% of siblings of affected patients
  • 10% have Down syndrome; another 5% have other serious neurologic impairment
  • Always affects rectum, usually also sigmoid, not other segments; anus and rectum usually small and devoid of stool
  • Symptoms: failure to pass meconium, obstructive constipation; may have occasional passage of stool or diarrhea if short segment of rectum affected
  • Complications: proximal innervated colon may become massively distended (15 cm in diameter) with muscular wall hypertrophy and rupture / perforation, usually near cecum or appendix; also acute intestinal obstruction, enterocolitis with fluid and electrolyte imbalance
  • Mortality: currently 5 - 10%
Diagnosis
  • Mucosal rectal biopsy with serial sections to detect ganglion cells (more irregular in submucosal plexus but process is less invasive than classic method of full thickness rectal biopsy; further identify in frozen section stained with acetylcholinesterase (see below); other diagnostic tests are contrast enema and anorectal manometry (J Pediatr Gastroenterol Nutr 2006;42:496)
  • Variability in cholinergic innervation may contribute to false negatives and false positives (Pediatr Dev Pathol 2008;11:274)
  • Classic method: biopsy muscular wall of rectum and examine for ganglion cells in myenteric plexus; should biopsy 2+ cm above anal valve in infants, 3+ cm in older children; if squamous epithelium present, must biopsy higher
  • Frozen sections: to document absence of ganglion cells and determine level of bowel transaction at surgery; also for acetylcholinesterase staining
Case reports
Treatment
  • Proctectomy with pull through of ganglionic bowel to anus; some patients have persistent bowel dysfunction (enterocolitis, constipation, incontinence)
Clinical images

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Slide tray

Gross description
  • Normal anus but small rectum and anal canal without stool, dilated proximal bowel
Gross images

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Dilated bowel

Microscopic (histologic) description
  • No ganglion cells in submucosal or myenteric plexus
  • No / reduced myenteric and muscular interstitial cells of Cajal in rectosigmoid colon
  • Thickening and hypertrophy of nonmyelinated nerve fibers and muscularis mucosa
  • Stercoral ulcers (sharply demarcated shallow ulcers with mucosal inflammation due to pressure of feces on obstructed colon)
  • Fibromuscular dysplasia of arteries between normal and diseased colon
  • Hypoganglionosis: arises between normal and aganglionic bowel; reduced number of ganglion cells (such as 10% of normal)
Microscopic (histologic) images

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Lack of ganglion cells

Increased acetylcholine positive nerve fibers

Hyperplastic nerves but no ganglion cells


Reduced interstitial cells of Cajal

Suction rectal biopsy specimen

Frozen sections

Segment of ileum and colon

Ganglion cells


Various images

Normal colon - calretinin+

Calretinin expression

Transitional zone - calretinin+

Normal ganglion cells: sympathetic ganglion cells

Positive stains
  • Acetylcholinesterase (increase in staining in lamina propria and muscularis mucosa reflects increase in nerve fibers, Pediatr Surg Int 2005;21:255)
Negative stains
Electron microscopy description
  • Altered cytoskeletal proteins in affected colon
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