Submucosal nerve diameter of greater than 40 μm is not a valid diagnostic index of transition zone pull-through

BackgroundSubmucosal nerve hypertrophy is a feature of the transition zone in Hirschsprung disease and has been used as a primary diagnostic feature of transition zone pull-through for patients with persistent obstructive symptoms after their initial surgery. Most published criteria for identification of hypertrophy rely on a nerve diameter of greater than 40 μm, based primarily on data from a relatively small number of infants with Hirschsprung disease and controls. The validity of these objective measures has not been validated in appropriate controls for post-pull-through patients.Scientific approachThe primary pull-through specimens and post pull-through biopsies +/− redo pull-through resections from a series of 9 patients with Hirschsprung disease were reviewed to assess the prevalence of submucosal nerves > 40 μm in diameter and 400 × microscopic fields containing two or more such nerves. Similar data from multiple colonic locations were collected from a series of 40 non-Hirschsprung autopsy and surgical controls.ResultsThe overwhelming majority of Hirschsprung patients harbored submucosal nerves > 40 μm in their post-pull-through specimens independent of other features of transition zone pathology, and despite normal innervation at the proximal margins of their initial resections. Measurement of submucosal nerve diameters in autopsy and surgical non-Hirschsprung control samples indicated that nerves > 40 μm are normal in the distal rectum after 1 year of age and are found in more proximal colon at older ages.ConclusionsThese results suggest that diagnostic criteria currently used to recognize submucosal nerve hypertrophy in the neorectum after a pull-through for Hirschsprung disease are not justified and should not be regarded as definitive evidence for transition zone pull-through.