Intestinal Neuronal Dysplasia Type B: One Giant Ganglion is Not Good Enough

Abstract

In this "Current Practice in Pediatric Pathology" article, 2 experts in the field and an associate editor of Pediatric and Developmental Pathology discuss the definition, diagnosis, clinical significance, and management of intestinal neuronal dysplasia type B. Intestinal neuronal dysplasia type B has constituted a diagnostic challenge ever since its first description more than 30 years ago. Intestinal neuronal dysplasia type B is regarded by many as a subtle malformation of the enteric nervous system that is limited to the submucosal plexus of the colon. The precise etiology remains unknown, and, to date, no specific diagnostic test exists other than morphology. Over time, with increasing experience, obligate pathological features have been adapted and refined, leading to contemporary diagnostic criteria that are enunciated in this review and placed into context with prior published data. Rigorous application of these criteria, under standardized laboratory conditions, is crucial for accurate diagnosis and future advances in this field.

Is the RET proto-oncogene involved in the pathogenesis of intestinal neuronal dysplasia type B?

“…We performed an exhaustive retrospective study of 23 patients presenting with INDB and 30 patients with a combined HSCR+INDB phenotype that were admitted to the Pediatric Surgery Unit of our hospital between 1980 and 2007. After the re-evaluation of all the biopsy specimens, INDB was histologically diagnosed according to the criteria updated by Meier-Ruge et al (3). Based on these criteria, diagnosis was performed when patients were over a year of age, and a minimum of 25 submucosal ganglia were randomly evaluated in the corresponding histological sections.…”

“…Children afflicted with INDB present with intractable constipation and grossly slowed intestinal transit time. Characteristic histologic features of INDB include hypoganglionosis of the submucous plexus, giant ganglia, ectopic ganglion cells and increased acetylcholinesterase activity in the lamina propria and around submucosal blood vessels (3). The clinical picture of INDB in some ways resembles Hirschsprung disease (HSCR, OMIM 142623), a congenital disorder characterized by the absence of intramural ganglion cells in the myenteric and submucosal plexuses along a variable portion of the distal intestine.…”

Intestinal Neuronal Dysplasia Type B: An Updated Review of a Problematic Diagnosis

“…Patients, particularly infants, often have spontaneous resolution of their symptoms with conservative medical management. 2,14,32 A few studies have evaluated retrospectively the clinical outcomes of patients receiving a diagnosis of IND B. Although the diagnostic criteria used in each of these investigations vary, conclusions regarding management are generally relatively uniform.…”

A new experimental approach is required in the molecular analysis of intestinal neuronal dysplasia type B patients

“…the clinical picture of indB resembles hirschsprung disease (hScr; Omim 142623), a congenital disorder characterized by the absence of intramural ganglion cells in the myenteric and submucosal plexuses along a variable portion of the distal intestine. indB does not include a region of aganglionosis, in absolute contrast to hScr, but as in hScr, it is reported to sometimes show increased extrinsic nerve fibers in the affected gut (2). In addition, some investigators have reported that 25-35% of patients with HSCR have associated INDB (2).…”

“…indB does not include a region of aganglionosis, in absolute contrast to hScr, but as in hScr, it is reported to sometimes show increased extrinsic nerve fibers in the affected gut (2). In addition, some investigators have reported that 25-35% of patients with HSCR have associated INDB (2). The lack of unified criteria for the diagnosis of indB has led to doubt regarding whether indB exists as a distinct histopathology entity.…”