Focal Hypoganglionosis-Associated Adult-Onset Megacolon: A Localized Enteric Neuropathy Distinct From Chronic Intestinal Pseudo-Obstruction

Adult-onset megacolon is a heterogeneous disorder traditionally classified within the spectrum of idiopathic megacolon or chronic intestinal pseudo-obstruction (CIPO). However, accumulating evidence suggests that a subset of patients demonstrates distinct clinicopathologic features characterized by localized motor dysfunction resulting in focal colonic narrowing, proximal megacolon, and localized hypoganglionosis. In this review, we refer to this phenotype as focal hypoganglionosis-associated adult-onset megacolon (FHAM). Clinically, patients with FHAM frequently present with severe chronic constipation, progressive abdominal distension and pain, nausea, vomiting, recurrent sub-occlusive or pseudo-obstructive episodes, and repeated decompressive interventions. Computed tomography typically demonstrates proximal megacolon with focal functional narrowing, whereas small bowel motility is preserved despite severe colonic dilatation. Histopathologic studies additionally demonstrated inflammatory ganglionitis associated with CD3-positive lymphocytic infiltration within the myenteric plexus. Molecular and physiologic studies of resected colonic tissue further revealed impaired neuromuscular signaling and smooth muscle contractility within the affected segment, suggesting localized enteric neuropathy as a potential pathogenic mechanism. Importantly, accumulating evidence suggests that patients with FHAM generally demonstrate favorable long-term outcomes following adequate surgical resection compared with patients with CIPO, including markedly lower rates of postoperative reoperation (2.5% vs. 66.7% with CIPO) and long-term total parenteral nutrition requirement (0% vs. 46.2% with CIPO). In summary, current evidence supports the concept that FHAM in adults represents a surgically remediable localized enteric neuropathic phenotype that can be clinically distinguished from classical CIPO. Recognition of this phenotype is clinically important because timely diagnosis and appropriate surgical intervention may substantially improve long-term outcomes.