Distal Rectal Skip-Segment Hirschsprung Disease and the Potential for False-Negative Diagnosis

Abstract

In skip-segment Hirschsprung disease (SS-HSCR), an aganglionic segment of bowel, which extends proximally from the distal rectum, is interrupted by a ganglionated "skip segment." Skip segments are usually located far proximal to the rectum where they do not interfere with initial diagnosis, although the possibility of distal SS-HSCR should be considered during interpretation of intraoperative biopsies or patients with atypical postoperative courses. We report 2 cases of SS-HSCR with skip areas in the distal rectum, 1 of which led to a false-negative diagnosis by suction rectal biopsy. These 2 cases of SS-HSCR, along with others in the literature, highlight the point that ganglionic skip segments can confuse clinicians and lead to inadequate bowel resection, diagnostic delay, or a false-negative diagnosis. The pathogenesis of SS-HSCR is discussed in light of recent discoveries regarding transmesenteric migration of vagal neural crest cells and the role of sacral neural crest cells in hindgut neurodevelopment.

Hirschsprung’s disease: clinical dysmorphology, genes, micro-RNAs, and future perspectives

“…Expression of calretinin, a vitamin D-dependent calcium-binding protein found in ganglion cells and nerves, has been described as an adjunctive or primary diagnostic test on gut biopsy specimens in HSCR with lack of specific calretinin staining confirming the diagnosis of aganglionosis (Figure 1d) (8). Classifying HSCR clinically is not an easy task, because the nervous system colonization failure may be variable or discontinuous (9,(13)(14)(15). Three phenotypes are usually recognized, including (i) total colonic aganglionosis (TCA), which involves the entire colon which is aganglionic with a potential proximal extension into varying lengths of small bowel (usually no more than 50 cm of small bowel proximal to the ileocaecal valve), (ii) total colonic and small bowel aganglionosis, which may involve very long segments of small bowel aganglionosis, and (iii) the more frequent rectal or rectal/sigmoid colonic aganglionosis (RA or RSCA).…”

“…Three phenotypes are usually recognized, including (i) total colonic aganglionosis (TCA), which involves the entire colon which is aganglionic with a potential proximal extension into varying lengths of small bowel (usually no more than 50 cm of small bowel proximal to the ileocaecal valve), (ii) total colonic and small bowel aganglionosis, which may involve very long segments of small bowel aganglionosis, and (iii) the more frequent rectal or rectal/sigmoid colonic aganglionosis (RA or RSCA). A debate over the definition and occurrence of several phenotypical entities, including the ultrashort segment and the skip-segmental aganglionosis is ongoing (13,(16)(17)(18)(19)(20)(21)(22). The majority of treatment remains surgical, while intense efforts are exploring the use of ENS stem cells by means of transplantation (12,23).…”

Skip segment Hirschsprung disease: modelling the trans-mesenteric origin of the enteric nervous system in the human colon

“…short segment HSCR) or ‘just succeeded’ (Binder et al, 2015). However skip lesions occur most frequently in a TCA context (Coe et al, 2016; O’Donnell and Puri, 2010), which is a major failure of colonisation. This suggests a greater reduction in ENC division rate is at play.…”

“…1 ). Combining the literature reviewed by O’ Donnell and Puri (O’Donnell and Puri, 2010), Ruiz et al (Ruiz et al, 2016) and Coe et al (Coe et al, 2016), there have been over 30 patients with skip-like ENS defects described since 1954. Most (>90%) skip segments have been detected in a TCA region (O’Donnell and Puri, 2010).…”

“…Assuming this trans-mesenteric event occurs in vivo as it does in organ cultures, then the stage at which this can occur is probably brief in vivo since further growth and morphogenesis increases the separation of the proximal and distal intestinal arms. This and other models have been incorporated in recent reviews (Coe et al, 2016; Sehgal, 2018), and this notion of Nishiyama and colleagues (Nishiyama et al, 2012) explains the occurrence and variable position of all skip segments better than the caecal by-pass model of Kapur and colleagues (Kapur et al, 1995).…”