Hirschsprung's Disease, One of the Most Difficult Diagnoses in Pediatric Surgery: A Review of the Problems from Clinical Practice to the Bench

Abstract

The rational, algorithmic diagnostic pathway proposed in this review paper aims to optimize every diagnosis by the stepwise application of a complementary set of procedures and enzyme-histochemical reactions as they become appropriate. In the interests of simplifying genetic molecular diagnosis, I suggest the following guidelines: 1) only in cases of total colonic aganglionosis (TCA) is it advisable to carry out full RET mutation screening (the mutation rate is up to 70 %); and 2) all HSCR patients should be tested only for standard MEN2A and MTC mutations. If these are present, the patients should be followed up carefully with proper surveillance and biochemical testing of other susceptible family members as they are at risk of developing neuroendocrine tumors.

Current practice patterns of rectal suction biopsy in the diagnostic work-up of Hirschsprung’s disease: results from an international survey

“…When properly oriented and cut adequately 50-75 sections should be generally sufficient to exclude the presence of submucosal ganglion cells [6,18]. This in turn requires an experienced histopathologist, who is familiar with the various staining methods used in the diagnostic work-up of HD, to avoid false-positive or false-negative results [27][28][29]. As a general rule, at least two formalin-fixed and paraffin-embedded samples are needed for routine histology with an additional specimen on saline wet gauze for enzyme immunohistochemistry of frozen sections.…”

Hirschsprung disease: current perspectives

“…Nevertheless, over 120 years later, "misunderstandings and diagnostic challenges still make it one of the most challenging diagnoses in certain cases". 4 This is mainly due to the interpretation of the findings and difficulties in separating it from allied congenital neurodysplastic conditions causing functional disturbances of the gastrointestinal tract (GIT).…”

Rectal suction biopsy for the diagnosis of Hirschsprung’s disease: a systematic review of diagnostic accuracy and complications

“…The diagnosis of HD can be difficult as it relies on histological confirmation of complete absence of enteric ganglion cells in the myenteric and submucosal plexus of the distal rectum, which extends proximally for varying distance. This requires an experienced histopathologist, who is familiar with the various staining methods used in the diagnostic work-up of HD including hematoxylin and eosin (H&E), acetylcholinesterase (AChE) and calretinin staining, in order to avoid false-positive or false-negative results [3][4][5].…”