Saire Mendoza M.1 Parajuli D.2 1Section of Gastroenterology and Hepatology, Ochsner Medical Center 2Division of Gastroenterology, Hepatology and Nutrition, University of Louisville
Intestinal ganglioneuromas can be found throughout the gastrointestinal tract and have three different presentations. They have been reported to be associated with multiple endocrine neoplasia type IIB (MEN-IIB), even before the GI endocrine neoplasms are diagnosed,1 and occasionally with Von Recklinghausen’s disease (VRD).2,3 These benign tumors are the result of submucosal (nerve) plexus hyperplasia in the intestinal wall,4 and consist of ganglion cells, nerve fibers and supporting cells. We report a case of a colonic ganglioneuroma found incidentally on screening colonoscopy. Management of these lesions, the risk of gastrointestinal malignancy and further assessment for occult non-gastrointestinal malignancies will be reviewed.
An otherwise healthy 69 year-old African American male underwent screening colonoscopy. A 1 cm subepithelial lesion, which was not characteristically adenomatous under both white light and narrow band imaging, was seen at the recto sigmoid junction (Figure 1). This lesion was biopsied and tattooed for future location. The initial sample did not yield a pathologic diagnosis thus rectal endoscopic ultrasound was performed. The lesion was noted to be hypoechoic and arising from the submucosa layer (Figure 2). Bite-on-bite cold forceps biopsies were taken and sent for histologic examination. The final pathologic findings were reported as a polypoid ganglioneuroma (Figure 3).
Intestinal ganglioneuromatous disease (GN) is divided into three groups.
- 1. Polypoid ganglioneuromas are small (<2cm), sessile or pedunculated polyps that are endoscopically difficult to distinguish from juvenile, hyperplastic or adenomatous polyps. Microscopically, they are divided into three patterns with disarranged crypt architecture with spindle and nerve ganglion cells within the mucosa being the most common.
- 2. Ganglioneuromatous polyposis (GP) consists of numerous, often 20 to 40, sessile or pedunculated lesions. There is less demarcation among the contents that make up the ganglioneuromas in this subgroup.
- 3. Diffuse ganglioneuromatosis (DG) presents as disseminated, nodular, intramural or transmural lesions ranging from 1 to 17cm in size and can lead to segmental bowel strictures; histologically these lesions involve the myenteric plexus. Most of DG cases are associated with MEN-IIB or VRD3,5,6; and may radiographically resemble Crohn’s disease on barium studies and computed tomography scans 7
The largest case series of ganglioneuromatosis was reported by Shekitka et al.3 in 1994 where 43 patients with intestinal ganglioneuromatous disease were followed. While some patients presented with abdominal pain, rectal bleeding or megacolon, many were asymptomatic. However, cases with watery diarrhea secondary to vasoactive intestinal polypeptide secretion and diffuse ganglioneuromatosis involving the colon and rectum have been reported,8,9 as well as upper GI bleeding from a ganglioneuroma of the duodenum10 and polypoid GN causing colonic intussusception.11
The prevalence of diffuse ganglioneuromatosis in patients with MEN-IIB syndrome is nearly 100%, and often gastrointestinal involvement predates the development of medullary thyroid cancer.1 Diarrhea or constipation from diffuse alimentary tract involvement, was reported in a case series of 16 patients with MEN-IIB.1 DG was found before medullary thyroid carcinoma in 12 of these16 cases. Therefore, the authors concluded that diffuse ganglioneuromatosis heralds the development of endocrine neoplasms, especially medullary thyroid carcinoma, which is the most common and most feared component of the MEN-IIB syndrome.
Around 25% of patients with Von Recklinghausen’s disease have shown some gastrointestinal involvement, mainly neurofibromas and occasionally ganglioneuromatosis.2,5 In one series, the mean interval between diagnosis of Von Recklinghausen’s disease and the onset of gastrointestinal symptoms related to gastrointestinal neurofibromatosis was approximately 37 years.2 Also, the simultaneous finding of diffuse ganglioneuromatosis and associated adenocarcinoma of the colon in patients with VRD5 seems to be more related to the high incidence of adenocarcinoma in patients with Von Recklinghausen’s disease12 rather than secondary to ganglioneuromatosis itself.
Polypoid ganglioneuromatosis and ganglioneuromatosis polyposis do not appear to be associated with systemic disorders such as MEN-IIB or VRD.3,6,13,14 Shekita et al.3 followed 16 patients with Polypoid GN and, after eight years, 13 were still alive and did not have evidence of MEN-IIB or VRD. Similar findings were obtained for patients with ganglioneuromatosis polyposis, however, two of the three patients had multiple skin tags and cutaneous tumors which were thought to be lipomas. Chan and colleagues6 also reported these cutaneous findings in patients with ganglioneuromatosis polyposis.
Intestinal ganglioneuromatosis has also been found in association with adenomatous, hyperplastic and juvenile type polyps.13,15 However, adenomas do not appear to be the prevailing feature in the setting of ganglioneuromatosis.
Three patterns of intestinal glanglioneuromatous disease have been described: polypoid ganglioneuromas, ganglioneuromatous polyposis (GP) and diffuse ganglioneuromatosis. Most cases of diffuse ganglioneuromatosis have been associated with MEN- IIB. The clinical presentation depends on size and location of ganglioneuromas. In diffuse gangliomatosis, gastrointestinal symptoms usually precede the development of thyroid medullary neoplasms and should prompt further diagnostic work up. There is not enough literature to suggest that intestinal ganglioneuromatosis has malignant potential.17 As such, an aggressive surgical approach in an asymptomatic patient without increased risk of carcinoma may be unnecessary.7 In the cases where GN is found along with hyperplastic or adenomatous polyps, current standard colonoscopy surveillance recommendations after polypectomy16 should be followed.
VRD: Von Recklinghausen’s disease
We thank Dr. Silvia D. Potenziani Pradella from the Department of Pathology and Laboratory Medicine at University of Louisville for contributing images of polypoid ganglioneuromatosis of the colon.