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Year : 2016  |  Volume : 59  |  Issue : 3  |  Page : 365-367
Isolated ileal ganglioneuromatosis in an 11-year-old boy: Case report and review of literature

Department of Pathology, AMRI Hospitals, Kolkata, West Bengal, India

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Date of Web Publication10-Aug-2016


Ganglioneuromatous proliferation in the gastrointestinal tract is a rare occurrence and is usually associated with specific syndrome complexes such as multiple endocrine neoplasia Type 2B or von Recklinghausen's disease. We report here a case of diffuse intestinal ganglioneuromatosis, presenting as intestinal obstruction and chronic constipation in an 11-year-old boy. Sporadic cases of intestinal ganglioneuromatosis in the absence of any systemic manifestations are a very rare cause of enteric motility disorders in childhood, and we discuss the pathological and clinical significance of this finding. Histopathological identification of this uncommon cause of a common pediatric problem is important since the condition is amenable to surgical treatment.

Keywords: Diffuse, ganglioneuromatosis, intestinal, isolated

How to cite this article:
Mitra S, Mukherjee S, Chakraborty H. Isolated ileal ganglioneuromatosis in an 11-year-old boy: Case report and review of literature. Indian J Pathol Microbiol 2016;59:365-7

How to cite this URL:
Mitra S, Mukherjee S, Chakraborty H. Isolated ileal ganglioneuromatosis in an 11-year-old boy: Case report and review of literature. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Jan 27];59:365-7. Available from: https://www.ijpmonline.org/text.asp?2016/59/3/365/188109

   Introduction Top

Diffuse ganglioneuromatosis (DGN) is one of the three forms of intestinal ganglioneuromas, other varieties being an isolated polyp or ganglioneuromatous polyposis.[1] The diffuse form is commonly associated with neurofibromatosis Type 1 (NF1) and multiple endocrine neoplasia Type 2B (MEN2B) or extraintestinal phenomena. This form has two variants, either mucosal or transmural, both seen in children.[2],[3] There is no confirmed link with intestinal malignancy, and resection of the affected segment is the only therapeutic option. Prognosis is variable depending on the severity of associated syndromes.[2],[4],[5]

   Case Report Top

An 11-year-old boy was admitted to the hospital with abdominal distension, vomiting, and absolute constipation for 4 days. There was no fever or weight loss and no lymphadenopathy or organomegaly. Routine laboratory investigations revealed normal hemoglobin level of 115 g/L, elevated leukocyte count with neutrophilia (white blood cell 15.8 × 109/L with 86% neutrophils), a normal platelet count of 380 × 109/L, and normal erythrocyte sedimentation rate.

Serum sodium (130 mmol/L) and serum creatinine (0.26 mg/dL) levels were mildly decreased while serum potassium (4.2 mmol/L) and urea (12.1 mg/dL) levels were normal. Serum C-reactive protein levels at 8.9 mg/L (n< 5 mg/L) were slightly elevated. Serological testing for hepatitis B surface antigen and antibodies to human immunodeficiency virus and hepatitis C virus were nonreactive.

Roentgenogram of the abdomen showed air trapped in dilated portion of small and large intestine with air-fluid levels. Computed tomographic scan of abdomen showed small bowel dilatation with air fluid level and a possible obstruction at the ileocecal junction. No evidence of ascites or mesenteric abnormality was found. Intra-abdominal organs were unremarkable [Figure 1].
Figure 1: (a) Computed tomography scan abdomen showing fluid collection in abdomen, indicated by arrow. (b) Computed tomography scan abdomen showing thickened intestinal wall, indicated by arrow. (c) Computed tomography scan abdomen showing thickened loop of ileum. (d) Dilated segment of ileum, with edematous wall, as seen on gross examination

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Laparatomy was done, and a 6 inch segment of distal ileum proximal to ileocecal junction was resected, with ileoileal anastomosis. Resected specimen was received for histopathological examination. Gross examination showed a dilated ileal segment with diffuse thickening of walls. Microsections revealed a normal mucosal lining and an edematous submucosa with extensive proliferation of ganglion cells, along with numerous hypertrophied nerve bundles extending through the muscular coat into the serosa. The mesenteric lymph nodes were reactive and surrounded by hypertrophied nerve bundles [Figure 2] and [Figure 3].
Figure 2: (a-c) Hypertrophied nerve bundles in edematous submucosa (H and E, ×100). (d) Reactive mesenteric lymph nodes surrounded by hypertrophied nerve bundles (H and E, ×100)

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Figure 3: (a-c) Clusters of ganglion cells in submucosa, indicated by arrows (a: H and E, ×100; b and c: H and E, ×400). (d) Section showing neuropil and ganglion cell proliferation in lamina propria, positive for S-100 (Immunoperoxidase, ×100)

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A diagnosis of DGN of small intestine was made. Detailed history taking, biochemical testing, and physical examination revealed no evidence of any preexisting symptoms of MEN2B or generalized NF1/von Recklinghausen's disease, and the disease complexes usually associated with intestinal DGN in children.

The family members were counselled, the patient treated symptomatically, and discharged uneventfully. He was symptom-free on repeat examination after a month and was lost to further follow-up.

   Discussion Top

Intestinal dysmotility disorders are common in pediatric patients, severest manifestations being chronic intestinal pseudo-obstruction in the absence of a mechanical obstructive lesion. Hirschprung disease or aganglionosis is best characterized of the pediatric gastrointestinal neuropathies, but other rarer causes can pose a diagnostic difficulty. Development of the enteric nervous system involves the migration and implantation of neural crest cells arising from the vagal neural crest.[6] Uncoordinated proliferation of the neural components is manifested as ganglioneuromatosis, existing as an isolated polyp, ganglioneuromatous polyposis, or DGN. Only the diffuse form is consistently associated with systemic disorders, DGN being seen in nearly all patients of MEN2B and in significant proportion of NF1 cases. Systemic disorders associated with DGN often show characteristic clinical stigmata such as mucosal neuromas and marfanoid habitus in MEN2B, cafe'-au-lait spots and cutaneous neurofibromas in NF1, or trichilemmomas and “cobblestone” tongue lesions in Cowden syndrome.[1],[2]

Children presenting with abdominal distension and obstructive symptoms in 1st year of life need to be investigated for DGN and initial manifestations of MEN2B. Radiographic studies may show circumferential intestinal wall thickening and lumen dilatation. Similar findings in adult patients are suggestive of Crohn's disease, especially when there is stricture formation.[1],[5],[7] Endoscopy is often inconclusive in DGN, and adequate thickness biopsies are required for histopathological diagnosis.

Morphology of DGN is distinctive on routine microsections.[8] There is diffuse, widespread proliferation of ganglion cells and hypertrophied nerve fibers. Earlier reports have demonstrated neuropil and ganglion cell proliferation in the lamina propria and submucosal layer, accompanied by a hyperplastic proliferation of the myenteric plexus, as seen in this case.[2] Neuronal cells are mature, with minimal pleomorphism or mitoses. Immunohistochemistry can be utilized, neurons being labeled by antibodies against neurofilaments, S-100, synaptophysin and tau protein. Ganglion cells are labelled by anti-c-Ret antibodies, and also by S-100 in several cases.[1],[2],[4],[6],[7] Ganglioneuromatous proliferations can occasionally be seen in the mesentery as illustrated by the hypertrophied nerve fibers closely apposed to the mesenteric lymph nodes in the current report. DGN exists as transmural and mucosal variants, both being seen in children. DGN in adults is more often mucosal and limited to colon and spares ileum.[6],[7]

Since transmural DGN is an early marker of MEN2B in infancy, further genetic, biochemical, and ancillary testing is warranted. Medullary thyroid carcinoma and adrenal pheochromocytoma develop early in such patients, and prompt surgical treatment is required to improve outcome. Similarly, patients of NF1 are at significant risk of developing malignancies, requiring early management.[6],[9]

The current report is uncommon due to the absence of a multi-systemic disorder in the patient other than DGN. Underlying genetic abnormalities are found in these syndrome complexes, usually abnormalities of tumor suppressor genes such as RET, PTEN, or NF1. Some reports have identified new genetic polymorphisms of the RET proto-oncogene in cases of isolated DGN.[10] Gain of function mutations in MEN2B usually arise de novo causing uncontrolled proliferation of tissues derived from neural crest cells.[2],[6]

There was none of the pathognomononic clinical or biochemical evidence of MEN or NF1 in this particular case, and DGN in MEN2B usually presents in infancy, unlike the current report. Genetic evaluation was not feasible in this case, but the patient had been advised regular surveillance by ultrasonography, serum calcitonin, and urinary catecholamine estimation.

DGN also needs to be distinguished from intestinal neuronal dysplasia (IND Type B) and digestive NF seen in NF1. NF can present as a nodular or diffuse submucosal proliferation of spindle cell bundles, without any ganglion cells.[7] IND Type B is a submucosal entity with giant ganglia and is of uncertain clinical significance.[6]

DGN identified on biopsies requires surgical resection of the affected segment. There is no established link with intestinal malignancy, and prognosis is good in cases of isolated DGN with no accompanying systemic disorders.[1],[2],[7]

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Conflicts of interest

There are no conflicts of interest.

   References Top

Shekitka KM, Sobin LH. Ganglioneuromas of the gastrointestinal tract. Relation to von Recklinghausen disease and other multiple tumor syndromes. Am J Surg Pathol 1994;18:250-7.  Back to cited text no. 1
Chan OT, Haghighi P. Hamartomatous polyps of the colon: Ganglioneuromatous, stromal, and lipomatous. Arch Pathol Lab Med 2006;130:1561-6.  Back to cited text no. 2
Ledwidge SF, Moorghen M, Longman RJ, Thomas MG. Adult transmural intestinal ganglioneuromatosis is not always associated with multiple endocrine neoplasia or neurofibromatosis: A case report. J Clin Pathol 2007;60:222-3.  Back to cited text no. 3
Siderits R, Hanna I, Baig Z, Godyn JJ. Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro-esophageal reflux disorder and intestinal metaplasia. World J Gastroenterol 2006;12:7874-7.  Back to cited text no. 4
Lefere I, Dalle I, Thieren H, Decock S, Ramboer K. Diffuse intestinal ganglioneuromatosis of the ileum. JBR BTR 2012;95:152-3.  Back to cited text no. 5
Schäppi MG, Staiano A, Milla PJ, Smith VV, Dias JA, Heuschkel R, et al. Apractical guide for the diagnosis of primary enteric nervous system disorders. J Pediatr Gastroenterol Nutr 2013;57:677-86.  Back to cited text no. 6
Chambonnière ML, Porcheron J, Scoazec JY, Audigier JC, Mosnier JF. Intestinal ganglioneuromatosis diagnosed in adult patients. Gastroenterol Clin Biol 2003;27:219-24.  Back to cited text no. 7
Smith VV, Eng C, Milla PJ. Intestinal ganglioneuromatosis and multiple endocrine neoplasia type 2B: Implications for treatment. Gut 1999;45:143-6.  Back to cited text no. 8
Tomita H, Miya K, Tanaka H, Shimokawa K. Ganglioneuroma and adenocarcinoma associated with neurofibromatosis type 1 in the colorectal region. Int J Colorectal Dis 2006;21:89-91.  Back to cited text no. 9
Nguyen AT, Zacharin MR, Smith M, Hardikar W. Isolated intestinal ganglioneuromatosis with a new mutation of RET proto-oncogene. Eur J Gastroenterol Hepatol 2006;18:803-5.  Back to cited text no. 10

Correspondence Address:
Dr. Subhashis Mitra
Department of Pathology, AMRI Hospitals, Kolkata - 700 029, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.188109

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  [Figure 1], [Figure 2], [Figure 3]

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