Lesions of the Lower Intestinal Tract
Moderators: Dr. Henry Appelman and Dr. Joel K. Greenson
Case 2 -
Adult Hirschprung's Disease
A 26-year-old woman reported to the emergency department complaining of many years of constipation.
She had previously been evaluated with colonoscopy, barium enema, and anal manometry, with all studies
being reported as normal. Her mother confirmed a negative workup for constipation during a
hospitalization at age 8 with slowly worsening symptoms since that time. There was no history of delayed
passage of meconium. Her family history was remarkable for similar constipation symptoms of unknown
origin in her mother and aunt. Upon physical examination she was emaciated with significant abdominal
distention and tympany to palpation. Her abdominal skin showed evidence of chronic distention.
Her laboratory studies were remarkable for an iron deficiency anemia and endocrine function tests
were within normal. An AP portable view of the abdomen revealed extensive fecal retention throughout the
colon. A CT scan confirmed severe colonic dilation along with extensive fecal loading and generalized
colonic wall thickening. The rectum was markedly dilated and there was no obstructive lesion
identified. Bowel rest, nasogastric tube decompression and daily enemas were effective over several
days. Additional studies were then performed. Flexible sigmoidoscopy revealed a markedly distended
colon. A small bowel follow-through showed displacement of the small bowel due to the distended colon
with a delayed transit time. Anal manometry showed a lack of a normal recto-anal inhibitory reflex.
Deep rectal biopsies were performed followed by a total proctocolectomy and ileal pouch anal anastomosis
with diverting loop ileostomy.
The lumen of the entire colon was packed with firm solid fecal material. The colon was massively
dilated, worse in the distal portion, with a maximal internal circumference up to 23 cm. The colonic
wall was thickened, up to 1.0 cm.
Case 2 - Slide 1
No ganglion cells were identified in the submucosa or between the muscular layers in the distal rectum
and up to 5.7 cm from the anal-rectal junction. Hypertrophic nerve bundles were present in this region.
Proximal to this aganglionic segment was a 2.6-cm hypoganglionotic segment or transitional zone where
rare ganglion cells and associated thick nerves were seen. The rest of the colon and small bowel showed
normal distribution of the ganglion cells.
Hirschsprung's disease (HD) is a congenital aganglionosis of the submucosal (Meissner's) and myenteric
(Auerbach's) neural plexuses principally affecting the rectosigmoid or rectal segments of varying
length. Most cases become manifest during the neonatal period but, in rare instances, the disease is
initially diagnosed in adults. In these cases, the patients have milder disease and go undiagnosed early
in their lives because the proximal innervated colon can be hypertrophied and, thus, compensates for the
distal obstructed, aganglionic rectum. In addition, these patients often try to relieve the constipation
by taking cathartics and using enemas. Eventually the dilated colon is no longer able to propel the
feces distally. These patients then develop rapidly worsening constipation or fecal retention.
The first recorded observation of HD is credited to Frederick Ruysch, who published an autopsy report
entitled "Enormis intestini coli dilatatio" in 1691. Nearly two centuries later, the disease was
reported in 1888 by Hirschsprung. It was not until 1948 that its pathogenesis was recognized.
Whitehouse and Kernohan documented the absence of ganglion cells in the myenteric plexus of Auerbach and
the submucosal plexus of Meissner in all patients with true congenital megacolon. Their findings led to
the development of an effective surgical treatment by Swenson and Bill in 1948.
HD affects approximately one in 5,000 livebirths and usually presents in infancy and early
childhood. Only a small number remain undetected after 5 years of age. Most cases of HD are felt to
have a genetic basis, and HD is a complex multigene disorder with incomplete penetrance and variable
associated anomalies. Mutations in greater than 11 genes have been implicated in HD, but mutations in
one or more of these genes are only detected in about half of HD making it likely that other genetic and
environmental factors are involved.
The primary pathogenic defect is the absence of ganglion cells of the submucosal (Meissner's) and
myenteric (Auerbach's) plexuses in the affected portion of the large bowel. The disease is thought to be
the result of defective migration of ganglion cell precursors of the neural crest into the hindgut.
Recent molecular studies have linked HD to defects in neural crest stem cell function. The aganglionic
segment in HD remains persistently contracted, whereas the proximal segment retains its peristaltic
function. As a result, there is work hypertrophy, eventual dilatation (megacolon), and sometimes
perforation of the normally innervated colon.
Adult Hirschsprung's disease
The term "adult Hirschsprung's disease" has been arbitrarily applied by some investigators to cases
in which the patient is older than ten years of age when the diagnosis is established. While others have
defined adult HD as cases in which the diagnosis was made after age 18 or 19. Although case reviews in
the English literature based on different diagnostic criteria have given different numbers of total
cases, the clinical presentation, radiologic features, and pathologic findings have been similar among
the various reports. Nearly 300 cases with at least some features of adult or adolescent HD have been
The typical adult patient with HD has a history of long-standing constipation since infancy or early
childhood and the male to female ratio is approximately 4:1. Patient age ranges from 10 to 73 years old,
and the average age is 24.1 years. Half of the patients are younger than 30. Other symptoms include
abdominal discomfort, distention and abdominal pain. Physical examination frequently reveals palpable
fecal masses. The patients tend to use cathartics, suppositories and enemas chronically to achieve bowel
movements. Fecal incontinence is not a feature in the adult patient in contrast to infants. Rectal
narrowing on barium enema is seen in three-quarters of the patients. However, in about 20% of the
patients with adult HD, a dilatated colon without characteristic rectal narrowing, as seen in our
patient, is demonstrated. This finding may be due to a short, or more commonly, an ultrashort diseased
segment. The exact incidence of adult HD is unknown because those cases are frequently misdiagnosed or
The diagnosis of HD in the adult can be much more difficult than the diagnosis in early infancy. This
is due to the rarity of the disease in adults and the higher incidence of short or ultrashort segment
aganglionosis with relative mild symptoms during the early stage of the disease. As in the newborns, the
diagnosis of HD in adults must be established by rectal biopsy showing absence of ganglion cells in the
distal rectum. Rectal biopsy should be performed only after more common causes of constipation and
megacolon have been ruled out. Constipation and acquired megacolon in adults may be due to neoplasm,
volvulus, stricture, slow colonic motility, Chagas disease, anatomical or functional outlet obstruction,
or idiopathic (non-Hirschsprung's) megacolon. Causes from external factors include dietary factors,
medications, psychological factors, and systemic diseases. Whenever there is a reasonable doubt,
manometric studies and biopsies are warranted.
The diagnosis of HD rests primarily upon barium enema, anorectal manometry and
rectal biopsy. The initial step is a barium enema study. The most reliable finding is a clear-cut zone
of transition between the aganglionic distal segment, which is narrow or of normal caliber, and the
dilated proximal colon with normal ganglion cells. The transition zone to the dilated segment is often
characterized as "funnel-shaped" or "inverted cone." Other signs may include retention of barium and the
mixing of barium and stool. Conventional radiography may demonstrate findings typically seen in most
other low small bowel obstructions such as variable gaseous distension of the colon and small bowel,
often with air-fluid levels. However, the colon is difficult to differentiate and gas is usually absent
in the rectum. CT scan may therefore be more useful for better anatomic delineation. Anorectal
manometry typically demonstrates no internal anal sphincter relaxation in response to rectal distension.
The diagnosis is confirmed by the rectal biopsy. A biopsy from the narrowed segment shows absence of
ganglion cells and may show hyperplasia and hypertrophy of nerve fibers, and an increased level of the
enzyme acetylcholinesterase (AchE). The initial biopsy is typically a suction rectal biopsy. Diagnostic
biopsies must be taken at least 1 to 1.5 cm proximal to the anorectal squamo-columnar junction and have
sufficient submucosa. Multiple levels are typically evaluated to identify ganglion cells. Hypertrophic
nerve fibers are observed in many cases and help establish the diagnosis. Some centers use frozen tissue
to help identify abnormally thick and numerous AchE-stained nerve fibers. In the resection specimen, the
Pathologist can then confirm the diagnosis, map the transitional zone and assess the proximal margin of
the resection for ganglion cells.
Adults with HD may present in an atypical fashion with massive dilatation of the
entire colon without rectal narrowing. The diagnosis may be easily overlooked or misdiagnosed in adult
patients with chronic constipation, particularly in the rare individual with ultrashort HD such as our
patient. Therefore, all patients who have severe chronic constipation since birth or childhood need a
thorough evaluation to rule out HD. The diagnosis can be suspected by barium enema and manometry, and
confirmed by rectal biopsy. Making the diagnosis of HD is extremely important since surgical management
is effective with satisfactory long-term functional results and significantly improved quality of
Fayu Chen, MD, at the Ohio State University assisted with the case diagnosis and the handout.
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