The Diagnostic Value of Immunohistochemistry Markers in Hirschsprung Disease; A Systematic Review and Meta-analysis

Immunohistochemistry (IHC) markers are employed to improve the diagnostic yield when testing for Hirschsprung disease (HSCR). Yet, a superior test has not been identified. We aimed to determine the diagnostic test accuracy (DTA) of IHC markers. We conducted database search for studies reporting IHC staining on rectal biopsy investigating for HSCR. We constructed 2 × 2 contingency tables, and calculated DTA estimates in pooled and paired testing using random-effect model meta-analysis. Twenty eight IHC markers from 107 studies were used to investigate for HSCR in 10891 children. In pooled analysis; calretinin sensitivity and specificity were superior to acetylcholinesterase, S100, and peripherin [98 % (CI; 0.95–0.99) & 99 % (CI; 0.97–0.99)], [94 % (CI; 0.86–0.97) & 99 % (CI; 0.96–0.99)], [92 % (CI; 0.85–0.96) & 97 % (CI; 0.89–0.99)] and [91.7 % (CI; 0.54–0.98) & 94.8 % (CI; 0.59–0.99)], respectively. In paired analysis calretinin diagnostic odds ratio was superior to hematoxylin and eosin (H&E), acetylcholinesterase and S100: [3349 (PI; 551.3–22667.2) vs 345.3 (PI; 54.9–2394.2)], [300.9 (PI; 13.3–4146.9) vs 34.6 (PI; 2.2–363.9)] and [696.9 (PI; 91.2–3401.7) vs 196.9 (PI; 29.8–890.5)], respectively. In biopsies labelled inadequate for H&E testing, calretinin specificity to rule out HSCR reached 92 % (CI; 0.288–0.998). IHC provides additional diagnostic value over H&E. Calretinin appears to be, currently, a superior IHC marker. The available literature is of variable quality, cautious interpretation of the findings should be considered. III. •What is currently known about this topic? Many immunohistochemistry markers have been used to improve the diagnostic accuracy when testing for Hirschsprung disease on rectal biopsy.•What new information is contained in this article? We report the staining characteristic and diagnostic accuracy of 28 distinct Immunohistochemistry markers used in the diagnosis of Hirschsprung disease. Calretinin demonstrate the best diagnostic test accuracy parameters, and seems superior to rule out Hirschsprung disease in inadequate rectal suction biopsy.