AJR 2004; 182:1166-1168
© American Roentgen Ray Society
Diffuse Intestinal Ganglioneuromatosis Mimicking Crohn's Disease
Sridhar R. Charagundla1,
Marc S. Levine1,
Drew A. Torigian1,
Mical S. Campbell2,
Emma E. Furth3 and
John Rombeau4
1 Department of Radiology, Hospital of the University of Pennsylvania, 3400
Spruce St., Philadelphia, PA 19104.
2 Department of Medicine, Hospital of the University of Pennsylvania,
Philadelphia, PA.
3 Department of Pathology, Hospital of the University of Pennsylvania,
Philadelphia, PA.
4 Department of Surgery, Hospital of the University of Pennsylvania,
Philadelphia, PA.
Received August 1, 2003;
accepted after revision September 23, 2003.
Address correspondence to M. S. Levine
(levine{at}oasis.rad.upenn.edu).
Introduction
Intestinal ganglioneuromatosis is a rare neoplastic condition characterized
by marked proliferation of ganglion cells, Schwann cells, and nerve fibers in
the wall of the bowel. This condition may affect any portion of the
gastrointestinal tract, but the ileum, colon, and appendix are most frequently
involved [1]. Certain forms of
intestinal ganglioneuromatosis lead to thickening and nodularity of the
intestinal wall with associated stricture formation
[2]. As a result, this
condition has been mistaken for Crohn's disease in the
non–English-language medical literature
[3,
4]. To our knowledge, however,
the findings of intestinal ganglioneuromatosis on barium studies or CT have
not been described previously in the radiologic literature. We therefore
present the imaging findings in a patient with the diffuse form of intestinal
ganglioneuromatosis.
Case Report
A previously healthy 53-year-old man presented to another hospital with
acute onset of bloody diarrhea, nausea, vomiting, and fever. His symptoms
persisted despite treatment with ciprofloxacin for suspected infectious
enteritis. Results of further workup with stool cultures, testing for
Clostridium difficile enterotoxin, and sigmoidoscopy were all
negative. A CT scan of the abdomen revealed thickening of the wall of distal
ileal loops, and small-bowel follow-through revealed a long segment of ileal
narrowing. A diagnosis of Crohn's disease was made on the basis of the
clinical and radiographic findings. Despite additional treatment with IV
steroids for 8 weeks and three infusions of infliximab (Remicade, Centocor),
the patient continued to have intractable diarrhea over the next 2 months. He
then was transferred to our hospital with a presumptive diagnosis of
refractory Crohn's disease.
A repeated small-bowel follow-through revealed a long segment of tubular
narrowing of the distal ileum with obliteration of folds and separation of
diseased loops from the adjacent small bowel
(Fig. 1A), and an oral and IV
contrast-enhanced CT scan of the abdomen 1 week later revealed mild ascites
with circumferential mural thickening of multiple ileal loops and
hypervascularity of the mesentery, producing a comb sign
(Fig. 1B). The findings on both
studies were thought to be compatible with advanced Crohn's disease of the
distal small bowel. Subsequent colonoscopy revealed a healthy colon but
abnormal terminal ileum with a granular mucosa and superficial erosions.
Endoscopic biopsy specimens from the terminal ileum revealed acute
inflammation without any definitive findings of Crohn's disease.
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Fig. 1A. —53-year-old man with diffuse intestinal ganglioneuromatosis
involving distal ileum. Frontal spot radiograph from small-bowel
follow-through shows long segment of tubular narrowing of distal ileum
(including terminal ileum) with obliteration of folds and separation of
diseased loops from adjacent small bowel. Note barium in cecum
(arrow).
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Fig. 1B. —53-year-old man with diffuse intestinal ganglioneuromatosis
involving distal ileum. Oral and IV contrast-enhanced CT scan of abdomen
obtained 1 week after A shows circumferential mural thickening of
multiple ileal loops (arrowheads). Also note dilatation and
prominence of arterial arcades and vasa recta in mesentery (arrows),
producing comb sign. Findings on barium study and CT were thought to be
compatible with Crohn's disease.
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The patient then underwent a laparotomy to obtain full-thickness biopsy
specimens from the diseased bowel. At surgery, the affected small bowel was
found to be extremely fragile, edematous, and friable, necessitating resection
of a long segment of distal ileum (not all of the diseased bowel was removed).
Pathologic examination of the resected specimen revealed extensive erosion of
the overlying mucosa, obliteration of the muscularis mucosae, and diffuse
infiltration of the submucosa by Schwann cells and ganglion cells, with normal
muscularis propria and surrounding fat
(Fig. 1C). The pathologic
findings were thought to be diagnostic of the diffuse form of intestinal
ganglioneuromatosis. The patient had a prolonged postoperative recovery,
complicated by wound and urinary tract infections, cholecystitis, and
gastrointestinal bleeding. After discharge, the patient developed recurrent
nausea, vomiting, and abdominal pain associated with small-bowel obstruction,
necessitating additional resection of the diseased small bowel.
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Fig. 1C. —53-year-old man with diffuse intestinal ganglioneuromatosis
involving distal ileum. Histomicrograph of resected ileum shows extensive
ganglioneuromatous infiltration of submucosa with scattered ganglion cells
(large arrow) and numerous spindle cells (small arrows),
which are Schwann cells with neural processes. (H and E, x400)
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Discussion
Intestinal ganglioneuromatosis is a rare, benign neoplastic condition
characterized by a spectrum of pathologic findings
[2]. Some patients have a
polypoid form of ganglioneuromatosis, manifested by solitary colonic polyps
composed of spindle cells and ganglion cells. Other patients develop multiple
polyps, most commonly in the colon and terminal ileum, a form of the disease
known as ganglioneuromatosis polyposis. Still other patients have a diffuse
form of intestinal ganglioneuromatosis characterized by hyperplasia of the
myenteric plexus and poorly circumscribed, infiltrative proliferation of
ganglioneuromatous tissue in the wall of the bowel. The latter form of disease
can be transmural, even affecting adjacent loops of the bowel. Diffuse
intestinal ganglioneuromatosis most commonly involves the colon, terminal
ileum, and appendix [2].
When the diffuse form of intestinal ganglioneuromatosis affects the distal
ileum, it can lead to marked thickening of the bowel wall, nodular submucosal
proliferations, and extensive stricture formation
[2]. Affected individuals may
present with marked diarrhea and abdominal pain
[2,
5]. In our patient, barium
studies of the small bowel revealed extensive tubular narrowing of ileal loops
with obliteration of folds and separation of the diseased ileum from adjacent
loops of bowel (Fig. 1A), and
CT revealed luminal narrowing and circumferential mural thickening of affected
ileal loops (Fig. 1B). CT also
revealed the comb sign with dilatation and prominence of the vasa recta in the
adjacent mesentery (Fig. 1B), a
finding attributed to increased blood flow and hypervascularity of the
affected bowel in Crohn's disease
[6].
Because of these abnormalities on barium studies and CT, ileal
ganglioneuromatosis could easily be mistaken for Crohn's disease on the basis
of the radiographic findings. In fact, cases of ileal ganglioneuromatosis
simulating Crohn's disease have been reported in the
non–English-language medical literature
[3,
4]. Other considerations in the
differential diagnosis of long segments of tubular narrowing and bowel wall
thickening in the distal ileum on barium studies and CT include chronic
ischemia or radiation change, cytomegalovirus, graft-versus-host disease,
lymphoma, and amyloidosis [7].
In such cases, however, the correct diagnosis can often be suggested on the
basis of clinical history and presentation. When nonspecific biopsy specimens
are obtained in patients with suspected Crohn's disease or these individuals
fail to respond to medical therapy for Crohn's disease, the possibility of
another cause for the disease, including ileal ganglioneuromatosis, should be
considered.
Treatment for the diffuse form of intestinal ganglioneuromatosis is
surgical resection of the diseased bowel due to poor response to medical
treatment. Intestinal ganglioneuromatosis is also known to be associated with
other potentially neoplastic conditions, including Cowden disease
[2,
8], neurofibromatosis 1
[2,
9], and multiple endocrine
neoplasia type 2B [2,
10]. Differentiation of
intestinal ganglioneuromatosis from Crohn's disease, therefore, has important
implications for patient treatment and prognosis.
In summary, we report a patient with the diffuse form of intestinal
ganglioneuromatosis in whom the clinical and radiographic findings mimicked
those of Crohn's disease. Despite its rarity, this condition should be
considered in patients with findings of Crohn's disease on barium studies and
CT who have intractable symptoms despite medical treatment.
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Introduction
Case Report
