Colon non tumor
Congenital anomalies
Hirschsprung’s disease

Author: Hanni Gulwani, M.D. (see Authors page)

Revised: 13 December 2016, last major update May 2013

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Hirschsprung’s disease[title]
Cite this page: Hirschsprungs disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/colonhirschsprung.html. Accessed August 18th, 2017.
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)
Gross description
  • Normal anus but small rectum and anal canal without stool, dilated proximal bowel
Gross images

Images hosted on other servers:

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

Images hosted on other servers:

Lack of ganglion cells

Increased acetylcholine positive nerve fibers

Hyperplastic nerves but no ganglion cells-1


Hyperplastic nerves but no ganglion cells-2

Reduced interstitial cells of Cajal

Suction rectal biopsy specimen

Frozen sections

Segment of ileum and colon


Slide tray

Ganglion cells

Various images

Calretinin


Normal colon - calretinin+

Calretinin expression

Transitional zone - calretinin+



Normal ganglion cells:

Sympathetic ganglion cells

Dorsal root of spinal cord


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