Hutson JM, Farmer PJ, Peck CJ, Chow CW, Southwell BR. Multiple endocrine neoplasia 2B: Differential increase in enteric nerve subgroups in muscle and mucosa. World J Gastrointest Pathophysiol 2017; 8(3): 142-149 [PMID: 28868184 DOI: 10.4291/wjgp.v8.i3.142]
Corresponding Author of This Article
Dr. Bridget R Southwell, Surgical Research/Gastrointestinal Motility Laboratory, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia. bridget.southwell@mcri.edu.au
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Pathophysiol. Aug 15, 2017; 8(3): 142-149 Published online Aug 15, 2017. doi: 10.4291/wjgp.v8.i3.142
Multiple endocrine neoplasia 2B: Differential increase in enteric nerve subgroups in muscle and mucosa
John M Hutson, Pam J Farmer, Cristal J Peck, Chung W Chow, Bridget R Southwell
John M Hutson, Pam J Farmer, Cristal J Peck, Bridget R Southwell, Surgical Research/Gastrointestinal Motility Laboratory, Murdoch Children’s Research Institute, Parkville, Victoria 3052, Australia
John M Hutson, Chung W Chow, Bridget R Southwell, Departments of Urology and Anatomical Pathology, The Royal Children’s Hospital, Parkville, Victoria 3052, Australia
John M Hutson, Bridget R Southwell, Department of Paediatrics, University of Melbourne, Melbourne 3010, Australia
Author contributions: Hutson JM surgeon managing patient and wrote manuscript; Farmer PJ and Peck CJ performed histology and immunohistochemistry and generated images; Chow CW provided pathological diagnosis; Southwell BR supervised study and revised manuscript.
Institutional review board statement: The study was performed under ethics approval to do further research on samples collected for diagnositc pathology. Royal Children’s Hospital Ethics Committee approval number 23081B and 24105.
Informed consent statement: The patient and his family gave written consent for the surgery where biopsies were collected for pathological assessment and verbal consent for the samples to be used in this study.
Conflict-of-interest statement: None of the authors has a conflict of interest as the surgery was performed for clinical indications and with informed consent and the histologic analysis was done with commercial reagents.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Bridget R Southwell, Surgical Research/Gastrointestinal Motility Laboratory, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia. bridget.southwell@mcri.edu.au
Telephone: +1-61-393455069 Fax: +1-61-393457997
Received: November 17, 2016 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
Abstract
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.
