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

Background-Intestinal neuronal dysplasia (IND) of the colonic submucous ple xus is considered to be a congenital malformation of the enteric nervous sy stem causing symptoms resembling those of Hirschsprung's disease. In contra st with the established diagnosis of aganglionosis using enzyme histochemis try, controversy exists over the diagnostic criteria of IND on rectal biops ies previously defined by a consensus report and the causal relation betwee n morphological findings and clinical symptoms. Aims-The interobserver variability was prospectively investigated with resp ect to final diagnoses and several histological features in rectal biopsy s pecimens 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 experi enced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and t he final diagnosis were analysed using Cohen's kappa statistic. Clinical da ta at biopsy and outcome after 12 months were related to morphological find ings. Results-The three pathologists agreed completely with respect to the diagno sis Hirschsprung's disease (kappa = 1), but in only 14% of the children wit hout aganglionosis. In 15 (17%) of the 87 children without aganglionosis, a t least one pathologist judged the case as normal, while another diagnosed IND. kappa values were close to the zero value expected by chance for the d iagnoses normal and IND. Young age was related to the presence of several m orphological features-for example, acetylcholine esterase staining and pres ence of giant ganglia. Children with chronic constipation diagnosed as havi ng 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 hav e no histological abnormalities (median 6.1 years, cure rate 23%). Conclusions-In contrast with Hirschsprung's disease, there is a high intero bserver variation with regard to the different morphological features and f inal diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in yo ung infants suggests that some of the features may represent a normal varia nt of postnatal development rather than a pathological process. Investigati ons using more refined and morphometric methods in rectal specimens from in fants and children without bowel disease are needed to define the normal ra nge of morphological appearance at different ages. These preliminary data i ndicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsp rung's disease.