A critical appraisal of the morphological criteria for diagnosing intestinal neuronal dysplasia type B

Abstract

Intestinal neuronal dysplasia type B is a controversial entity expressed by complex changes in the enteric nervous system. Diagnosis depends on rectal biopsy histopathology and diagnostic criteria, both qualitative and quantitative, have changed over time, hindering the diagnostic practice. We analyzed the morphological criteria for the histological diagnosis of intestinal neuronal dysplasia type B in a series of patients with intestinal neuronal dysplasia type B according to the 1990 Frankfurt Consensus criteria and verified the applicability of the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. Qualitative criteria adopted for the histological diagnosis of intestinal neuronal dysplasia type B included hyperplasia of the submucous plexus with hyperganglionosis and hypertrophy of the nerve trunks. Quantitative criteria considered more than 20% giant ganglia in the submucosa, with more than eight neurons each on 25 ganglia, and children aged over 1 year. Distal colon surgical specimens from 29 patients, aged 0-16 years, diagnosed with intestinal neuronal dysplasia type B were retrospectively analyzed using sections processed for conventional histology (H&E) and calretinin immunohistochemistry. Hyperplasia of the submucosal nerve plexi with hyperganglionosis and hypertrophy of the nerve trunks was observed in all cases. Ganglia with small, immature neurons were detected in the majority of cases. Quantitative analysis confirmed hyperganglionosis (mean number=10.7 neurons per ganglion) and hypertrophy of the nerve trunks (median=44.6 μm thickness). Neurons showed immunostaining for calretinin, but neuron counts in calretinin-stained sections were lower compared with H&E (P<0.01). No significant differences were verified between children aged under and over 1 year regarding hyperganglionosis (P=0.79), neuron counts (P=0.36), and immature ganglia (P=0.66). Only one patient met the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. In conclusion, the numerical criteria showed limited applicability when transposed to conventional histopathology. Children aged over 1 year presented very similar histological features of neuronal immaturity to younger children, questioning the need for an age criterion when diagnosing intestinal neuronal dysplasia type B.

Intestinal Neuronal Dysplasia Type B: An Updated Review of a Problematic Diagnosis

“…13 In some centers, most IND B patients who failed conservative management are treated successfully by anal sphincter myomectomy. It seems likely that the IND B patients evaluated by Terra et al 39 failed medical management and represent a clinically severe end of the IND B spectrum. As such, their pathology may be different from that of most IND B patients, further complicating interpretation of their results.…”

“…Nonetheless, colonic resection for IND B appears to be a frequent practice at 1 institution, where at least 29 pediatric patients underwent surgery to treat isolated IND B. 39 An algorithm that has been published from a different center suggests that before a pull-through procedure is completed, patients with HSCR should undergo serial biopsies of their ganglionic colon to exclude IND B. 66,67 We believe that insufficient evidence exists to support either of these practices and we also believe that, despite the fact that it has been nearly 5 decades since IND B was first described, it is still best regarded as an inconsistently defined histopathologic phenotype with uncertain clinical relevance.…”

Effect of Neuroligin1 and Neurexin1 on the Colonic Motility in a Mouse Model of Neuronal Intestinal Dysplasia

“…Neuronal intestinal dysplasia (NID) is a clinical condition that resembles Hirschsprung's disease (HSCR) and is clinically characterized by seriously impaired colonic motility, such as severe constipation or intestinal obstruction [1,2]. Different from HSCR in histologically observation, absence of ganglion cells in the myenteric plexus, patients with NID show hyperplasia of the submucous and myenteric plexus with increase in AChE-positive nerve fibers [3].…”

Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B

“…Patients typically present with severe intestinal constipation, sometimes complicated by episodes of intestinal obstruction 2 . IND-B diagnosis relies on the histopathological analysis of rectal biopsies by identifying the hyperplasia of the submucosal nerve plexus 1,3 , which is characterized according to different criteria 1,4–6 . Despite the intense scientific research that has been performed in recent decades, IND-B still remains with uncertainties regarding its definition, etiopathogenesis, diagnostic criteria and treatment 2,7,8 .…”