Calretinin-Immunoreactive Mucosal Innervation in Very Short-Segment Hirschsprung Disease: A Potentially Misleading Observation

Absent calretinin-immunoreactive (CRir) mucosal innervation in aganglionic rectal biopsies is considered a useful diagnostic finding for Hirschsprung disease. Analysis of a series of rectosigmoid resections from patients with short-segment (>2-cm aganglionic, n = 9) and very short-segment (<= 2-cm aganglionic, n = 9) Hirschsprung disease demonstrates that CRir mucosal nerves extend into the proximal 1-2 cm of aganglionic bowel, where their presence in distal rectal biopsies could complicate diagnosis of very short-segment disease. Indeed, retrospective analysis of preoperative, aganglionic, distal rectal biopsies from 4 of 9 patients with very short-segment Hirschsprung disease revealed CRir mucosal innervation. Accurate diagnosis was possible based on generous histopathological submucosal sampling to exclude ganglion cells and the presence of abundant large-caliber submucosal nerves (more than 4 nerves >30 mu m thick/x200 field or more than 2 nerves >40 mu m thick/x200 field). Absent CRir mucosal innervation supports the diagnosis of Hirschsprung disease, but the presence of CRir mucosal nerves does not exclude aganglionosis, especially in distal rectal biopsies from patients with very short-segment Hirschsprung disease.