Anus and perianal area
Benign or nonneoplastic lesions
Hirschsprung disease

Author: Elliot Weisenberg, M.D. (see Authors page)

Revised: 3 October 2017, last major update July 2014

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PubMed Search: "Hirschsprung disease" anus "loattrfree full text"[sb]

Cite this page: Weisenberg, E. Hirschsprung disease. PathologyOutlines.com website. http://pathologyoutlines.com/topic/anushirschsprung.html. Accessed October 22nd, 2017.
Definition / general
  • Loss of parasympathetic ganglion cells in distal large bowel extending proximally for a variable distance that leads to bowel obstruction with dilation of bowel proximal to the involved segment
Terminology
  • Synonyms include aganglionosis coli, aganglionic megacolon, congenital megacolon
Epidemiology
  • Most sources: 1 in 5000 live births, some as low as 1 in 30,000
  • General agreement on male predominance (3 to 4.5:1)
  • Approximately 10% associated with Down syndrome
  • Up to 15% have other conditions
  • About 5% have neurologic abnormalities that may be serious
  • Associated with intestinal atresia and malrotation, anorectal malformations and other abnormalities of the GI tract
  • Also associated with tumors and other syndromes
  • 5% have a sibling with disease; familial cases have also been reported
  • Patients usually present in the immediate perinatal period; 80% present before their first birthday but up to 10% of cases are diagnosed in adulthood
Sites
  • Most authorities describes six forms that correspond to the location and length of the aganglionic segment
  • Classic form: starts just proximal to pectinate line and extends proximally for a variable distance
  • Short segment form: aganglionic segment may be as short as 3 cm
  • Long segment form: aganglionic segment involves at least the entire rectum and sigmoid
  • Total colonic aganglionosis: entire large bowel lacks ganglia and variable length of small intestine is affected
  • Zonal colonic aganglionosis: ganglia are found distal to aganglionic segment
    • Some investigators believe zonal colonic aganglionosis is not true Hirschsprung disease but due to in utero injury
  • Approximately 90% of cases are classic or short segment type
Pathophysiology
  • The absence of parasympathetic ganglia causes a loss of intrinsic inhibitory innervation that leads to continuous contraction of the involved segment, as well as an inability of the affected segment to relax in response to a peristaltic wave
  • As the disease progresses, the bowel proximal to the aganglionic segment undergoes muscular hypertrophy and dilation
Etiology
  • The proximate cause is failure of migration of parasympathetic ganglia from the neural crest; however, several genetic abnormalities have been described
  • It is probably best regarded as a genetic disorder having a complex and poorly understood inheritance pattern involving at least 8 genes
  • The RET protooncogene appears to play a prominent role in many cases and dozens of RET mutations have been described (Histol Histopathol 2013;28:1117)
  • Increased MHC class II antigens have been found in the aganglionic segment and some investigators believe that in some cases, the disease may have an immune mediated component
Clinical features
  • The most common presentation is delayed passage of meconium associated with abdominal distension and anal tightness in the first 1 - 2 days of life
  • Children may have failure to thrive
  • Down syndrome patients more commonly have associated enterocolitis
  • Older patients may present with chronic constipation, abdominal distension, vomiting
Diagnosis
  • Diagnosis is usually suspected clinically - the pathologist is in the difficult position of trying to prove a negative
  • Most cases are diagnosed with a full thickness suction biopsy that contains the mucosa and submucosa
  • It has been established that absence of ganglia in Meissner submucosal plexus corresponds to absence in Auerbach plexus (see Microscopic (histologic) description)
  • Rare cases require full thickness excisional biopsy to establish the diagnosis, which requires general anesthesia with greater risk of complications
  • Most protocols recommend two biopsies 2 cm above the anal valve in infants and 3 cm in older patients
  • If the biopsy contains squamous or transitional epithelium, it likely is inadequate
  • Institution specific protocols involving multiple levels (in some cases up to 100 levels) and special stains (immunohistochemistry or histochemical stains sometimes requiring frozen tissue) should be instituted to ensure accurate reporting of aganglionosis
Case reports
  • Novel association of severe neonatal encephalopathy and Hirschsprung disease in a man with a duplication at the Xq28 region (BMC Med Genet 2010;11:137)
  • Patient with hydrocephalus, vesico - ureteral reflux and a balanced translocation t(3;17)(p12;q11) (Eur J Hum Genet 2009;17:483)
Treatment
  • Surgical: excision of aganglionic segment with a pull through procedure to achieve continence; successful in most cases
  • Frozen section may be obtained during the procedure to determine where ganglionic segment begins but the accuracy of this technique is inferior to usual frozen section
    • Use of Giemsa, Diff-Quik, or toluidine blue stains in addition to routine H&E has been advocated to improve diagnostic accuracy at frozen section
  • Most patients are successfully treated
  • Treatment failures may have abnormal ganglion cells anastomosed to anorectum or subsequently develop aganglionosis
Microscopic (histologic) description
  • There is a complete absence of ganglia in both Meissner submucosal plexus and Auerbach myenteric plexus
  • Ganglia in newborns are smaller than in older children and nucleoli and Nissl substance may be lacking, a situation even more pronounced in premature infants
  • Ganglia near the junction of the ganglionic and aganglionic segment may be decreased in number or be small with abnormal staining patterns
  • Associated nerve hypertrophy is a helpful clue but is not diagnostic
  • Some studies have shown a marked reduction or absence of interstitial cells of Cajal in the internal anal sphincter (Arch Pathol Lab Med 2003;127:1192) but this is not universally accepted
Microscopic (histologic) images

Images hosted on other servers:
Missing Image

Reduction of nerve fibers and interstitial cells

Immunohistochemistry
Differential diagnosis
  • Chronic idiopathic pseudo-obstruction
  • Enteric hypoganglionosis syndromes
  • Hyperplasia of myenteric plexus: may occur secondary to inflammation in idiopathic inflammatory bowel disease or neurofibromatosis