Some patients continue to have obstructive symptoms and/or incontinence after pullthrough surgery for Hirschsprung disease. Incontinence can be due to injury to the anal sphincter and/or dentate line, abnormal colonic motility (nonretentive), or a chronic large stool burden (retentive). A diagnostic algorithm based on clinical and pathological evaluations can be applied to distinguish potential etiologies for obstructive symptoms, which segregate into anatomic (mechanical or histopathological) or physiologic subgroups. Valuable clinical information may be obtained by anorectal examination under anesthesia, radiographic studies, and anorectal or colonic manometry. In addition, histopathological review of a patient\'s original resection specimen(s) as well as postoperative biopsies of the neorectum usually are an important component of the diagnostic workup. Goals for the surgical pathologist are to exclude incomplete resection of the aganglionic segment or transition zone and to identify other neuromuscular pathology that might explain the patient\'s dysmotility. Diagnoses established from a combination of clinical and pathological data dramatically alter management strategies. In rare instances, reoperative pullthrough surgery is required, in which case the pathologist must be aware of histopathological features specific to redo pullthrough resection specimens.

Varied intestinal neuromuscular pathologies are responsible for Hirschsprung disease and other forms of chronic pseudo-obstruction that are encountered in pediatrics. Pathologically distinct subtypes discussed in this review include aganglionosis, hypoganglionosis, neuronal intranuclear inclusion disease, ganglionitis, degenerative neuropathy, diffuse ganglioneuromatosis, neuronal dysplasia, malformations of the muscularis propria, degenerative leiomyopathy, leiomyositis, and mitochondriopathies. Emphasis is given to the histopathologic features that distinguish these conditions and their differential diagnoses.

Intestinal neuronal dysplasia type B (IND) denotes an increased proportion of hyperplastic submucosal ganglia, as resolved histochemically in 15-μm-thick frozen sections. IND has been reported proximal to the aganglionic segment in patients with Hirschsprung disease (HSCR) and is putatively associated with a higher rate of postsurgical dysmotility. We developed and validated histological criteria to diagnose IND-like submucosal ganglion cell hyperplasia (IND-SH) in paraffin sections and used the approach to study the incidence and clinical and/or genetic associations of IND-SH at the proximal margins of HSCR pull-through resection specimens. Full-circumference paraffin sections from the proximal margins of 64 HSCR colonic pull-through specimens and 24 autopsy controls were immunostained for neuron-specific Hu antigen, and nucleated ganglion cells in each submucosal ganglion were counted. In controls, an age-related decline in the relative abundance of \"giant\" ganglia (≥7 nucleated Hu-positive [Hu+] ganglion cells) was observed. A conservative diagnostic threshold for IND-SH (control mean ± 3× standard deviation) was derived from 15 controls less than 25 weeks of age. No control exceeded this threshold, whereas in the same age range, IND-SH was observed at the proximal margins in 15% (7 of 46) of HSCR resections, up to 15 cm proximal to the aganglionic segment. No significant correlation was observed between IND-SH and length of or distance from the aganglionic segment, sex, trisomy 21, RET or SEMA3C/D polymorphisms, or clinical outcome, but analysis of more patients, with better long-term follow-up will be required to clarify the significance of this histological phenotype.