Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome

Abstract

Background-Intestinal neuronal dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung's disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. Aims-The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. Methods-377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen's statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. Results-The three pathologists agreed completely with respect to the diagnosis Hirschsprung's disease ( = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features-for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%).Conclusions-In contrast with Hirschsprung's disease, there is a high interobserver variation with regard to the diVerent morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at diVerent ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung's disease. (Gut 1999;44:853-861)

A Practical Guide for the Diagnosis of Primary Enteric Nervous System Disorders

“…The easiest means of obtaining adequate diagnostic tissue in rectal biopsies in infants is by rectal suction biopsy (RSB) (18). These provide larger and deeper biopsies than standard endoscopic forceps biopsies, which are usually inadequate to obtain sufficient submucosa and therefore are not recommended (19,72) (Fig. 2).…”

Study of acetylcholinesterase activity in rectal suction biopsy for diagnosis of intestinal dysganglionoses: 17-year experience of a single center

“…The study of the ressected specimen of the intestine demonstrated alterations that were suggestive of the diagnosis of neuronal intestinal dysplasia. Although the existence of this nosocomial entity had been suggested at the fourth international symposium on Hirschsprung disease and related neurocristopathies, it is not clear if it is a separate primary entity or some sort of acquired condition [11,19]. Our cases were pre-school aged children with severe constipation and huge colonic dilatations with or without significant dilatation of the small bowel and duodenum.…”

Intestinal neuronal dysplasia type B: A still little known diagnosis for organic causes of intestinal chronic constipation

“…Other morphological features, such as the presence of ectopic ganglion cells, increased acetylcholinesterase activity, ganglion cells with a "button" appearance and hypertrophy of the nerve trunks, are considered diagnostic criteria in some studies [9,10,16,68,79,91] . The criteria described by MeierRuge et al [22] (2004) and slightly altered by MeierRouge et al [5] [5,77,92] .…”