Published online Aug 15, 2017. doi: 10.4291/wjgp.v8.i3.142
Peer-review started: November 22, 2016
First decision: February 30, 2017
Revised: May 24, 2017
Accepted: July 14, 2017
Article in press: July 17, 2017
Published online: August 15, 2017
Processing time: 269 Days and 18.4 Hours
Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome caused by an activating mutation of the RET gene, leading to enteric gangliomatosis. This child presented with constipation at 1-mo old, was diagnosed with MEN2B by rectal biopsy at 4 mo, had thyroidectomy at 9 mo and a colectomy at 4 years. We studied the extent of neuronal and nerve fibre proliferation and which classes of enteric nerves are affected by examining the colon with multiple neuronal antibodies. Resected transverse colon was fixed, frozen, sectioned and processed for fluorescence immunohistochemistry labelling with antibodies against TUJ1, Hu, ChAT, NOS, VIP, SP and CGRP and cKit. Control transverse colon was from the normal margin of Hirschsprung (HSCR) colon (4-year-old) and a child with familial adenomatous polyposis (FAP, 12 year). Myenteric ganglia were increased in size to as wide as the circular muscle. There was a large increase in nerve cells and nerve fibres. ChAT-, NOS-, VIP- and SP-immunoreactive nerve fibres all increased in the myenteric ganglia. NOS-IR nerves preferentially increased in the muscle, while VIP and SP increased in submucosal ganglia and mucosal nerve fibres. The density of ICC was normal. RET overactivation in MEN2B lead to a large increase in intrinsic nerve fibres in the myenteric and submucosal ganglia, with a relative increase in NOS-IR nerve fibres in the circular muscle and VIP and SP in the submucosal ganglia and mucosa. The changes were associated with severe constipation resulting in colectomy at 4 years.
Core tip: Multiple endocrine neoplasia (MEN) 2B is a rare anomaly caused by an activating mutation of the RET known to produce enteric gangliomatosis. Thyroidectomy is performed to avoid cancer and the colon removed to overcome the constipation. This child presented with constipation very early (1-mo-old) and had subtotal colectomy at 4 years. The classes of nerves affected in MEN2B colon have not been studied before. We used immunohistochemistry with multiple antibodies. There was a massive increase in intrinsic nerve fibres in myenteric and submucosal ganglia, with a differential increase in types of nerve fibres in the muscle and mucosa.