{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:18:49Z","timestamp":1787840329164,"version":"build-2784847793"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The normal motility of the gastrointestinal tract depends on the enteric nervous system, the smooth muscle, and the interstitial cells of Cajal (ICC). Hirschsprung\u2019s disease (HD) is the most common motility disorder in the pediatric age group, which needs to be differentiated from other motility disorders, especially intestinal neuronal dysplasia- type B (IND-B). The aim of this study is to analyze the distribution of ICCs in HD and IND-B with reference to location and density as well as to evaluate the importance of submucosal nerve trunk thickness in differentiating HD from IND-B.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>The distribution and number of ICCs were assessed by immunohistochemistry. ICCs were evaluated in the inner circular layer, outer longitudinal layer, and the myenteric plexus. The presence of hyperganglionosis, giant ganglia, and ectopic ganglia was assessed in IND-B and compared to the controls. Immunohistochemistry was performed for CD 117 (c-kit) and Anoctamin-1 (Ano-1) to identify the ICCs, along with synaptophysin and S-100 for identification of the ganglion cells and nerve bundles, respectively. The submucosal nerve trunk thickness was evaluated by nerve trunk morphometry in all three groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      ICCs were significantly reduced in all three layers in IND-B and HD as compared to the normal controls (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      value &lt; 0.5). The cases of IND-B showed a significant reduction of ICCs in the inner circular and outer longitudinal layers as compared to HD, while the number of ICCs in the myenteric plexus was similar in these groups. The nerve trunk thickness was found to be significantly higher in HD and IND-B compared to the normal controls with IND-B showing even higher submucosal nerve trunk thickness than HD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our findings suggest that there is a significant difference in the distribution of ICCs in the two muscular layers of HD and IND-B. Further multicenter studies are required to evaluate the utility of ICCs as a potential marker for differentiating HD from IND-B. Although nerve trunk thickness greater than 40 \u03bc can be useful in differentiating HD from other non-motility disorders, it cannot be used to distinguish HD from IND-B.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijpm.ijpm_574_24","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T16:01:07Z","timestamp":1755532867000},"page":"703-709","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Significance of interstitial cells of Cajal in Hirschsprung\u2019s disease and intestinal neuronal dysplasia \u2013 A comparative study"],"prefix":"10.4103","volume":"68","author":[{"given":"Aniket","family":"Halder","sequence":"first","affiliation":[{"name":"Department of GI Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdous Wasim","family":"Sk","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman Kumar","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranajoy","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of GI Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibsankar","family":"Barman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchirendu","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uttara","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"R1-20251208","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nm0798-848","article-title":"Interstitial cells of Cajal generate a rhythmic pacemaker current","volume":"4","author":"Thomsen","year":"1998","journal-title":"Nat Med"},{"key":"R2-20251208","doi-asserted-by":"crossref","first-page":"G1129","DOI":"10.1152\/ajpgi.2001.281.5.G1129","article-title":"Gastric motility:Lessons from mutant mice on slow waves and innervation","volume":"281","author":"Huizinga","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R3-20251208","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1053\/j.sempedsurg.2009.07.002","article-title":"The histopathology of gastrointestinal motility disorders in children","volume":"18","author":"Feichter","year":"2009","journal-title":"Semin Pediatr Surg"},{"key":"R4-20251208","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00383-013-3351-3","article-title":"Classification and diagnostic criteria of variants of Hirschprung's disease","volume":"29","author":"Friedmacher","year":"2013","journal-title":"Paediatr Surg Int"},{"key":"R5-20251208","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0022-3468(95)90051-9","article-title":"A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung's disease","volume":"30","author":"Yamataka","year":"1995","journal-title":"J Pediatr Surg"},{"key":"R6-20251208","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S1055-8586(98)70015-0","article-title":"Intestinal neuronal dysplasia","volume":"7","author":"Puri","year":"1998","journal-title":"Semin Pediatr Surg"},{"key":"R7-20251208","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1053\/j.sempedsurg.2012.07.005","article-title":"Variants of Hirschsprung's disease","volume":"21","author":"Puri","year":"2012","journal-title":"Semin Paediatr Surg"},{"key":"R8-20251208","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1016\/j.jpedsurg.2019.06.003","article-title":"Clinicopathological study of intestinal smooth muscles, interstitial cells of Cajal, and enteric neurons in neonatal jejuno-ileal atresia with special reference to muscle morphometry","volume":"54","author":"Saha","year":"2019","journal-title":"J Pediatr Surg"},{"key":"R9-20251208","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/modpathol.2009.110","article-title":"Calretinin immunohistochemistry:a simple and efficient tool to diagnose Hirschsprung disease","volume":"22","author":"Guinard-Samuel","year":"2009","journal-title":"Mod Pathol"},{"key":"R10-20251208","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1097\/01.pas.0000166365.83706.e6","article-title":"Immunohistochemical studies of pediatric intestinal pseudo-obstruction:bcl2, a valuable biomarker to detect immature enteric ganglion cells","volume":"29","author":"Park","year":"2005","journal-title":"Am J Surg Pathol"},{"key":"R11-20251208","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00383-010-2828-6","article-title":"A role for Pten in paediatric intestinal dysmotility disorders","volume":"27","author":"O'Donnell","year":"2011","journal-title":"Pediatr Surg Int"},{"key":"R12-20251208","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.5858\/1999-123-1264-EOBIEN","article-title":"Expression of bcl-2 in enteric neurons in normal human bowel and Hirschsprung disease","volume":"123","author":"Wester","year":"1999","journal-title":"Arch Pathol Lab Med"},{"key":"R13-20251208","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1007\/s00383-003-1026-1","article-title":"Interstitial cells of Cajal are normally distributed in both ganglionated and aganglionic bowel in Hirschsprung's disease","volume":"19","author":"Newman","year":"2003","journal-title":"Pediatr Surg Int"},{"key":"R14-20251208","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1053\/gast.1996.v111.pm8690216","article-title":"A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract","volume":"111","author":"Sanders","year":"1996","journal-title":"Gastroenterology"},{"key":"R15-20251208","doi-asserted-by":"crossref","first-page":"928","DOI":"10.5858\/2002-126-0928-ADOICO","article-title":"Altered distribution of interstitial cells of Cajal in Hirschsprung's disease","volume":"126","author":"Rolle","year":"2002","journal-title":"Arch Pathol Lab Med"},{"key":"R16-20251208","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S0016-5085(96)70057-4","article-title":"Interstitial cells of Cajal in the colon and in the Hirschsprung's Disease","volume":"111","author":"Vanderwinden","year":"1996","journal-title":"Gastroenterology"},{"key":"R17-20251208","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1007\/s00383-007-2022-7","article-title":"Interstitial cells of Cajal in the normal gut and in intestinal motility disorders of childhood","volume":"23","author":"Rolle","year":"2007","journal-title":"Pediatr Surg Int"},{"key":"R18-20251208","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/S0022-3468(97)90401-2","article-title":"Intestinal pacemaker C-KIT+cells and synapses in allied Hirschsprung's disorders","volume":"32","author":"Yamataka","year":"1997","journal-title":"J Pediatr Surg"},{"key":"R19-20251208","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1097\/00000478-200011000-00016","article-title":"Congenital interstitial cell of cajal hyperplasia with neuronal intestinal dysplasia","volume":"24","author":"Jeng","year":"2000","journal-title":"Am J Surg Pathol"},{"key":"R20-20251208","first-page":"345","article-title":"Immunohistochemical study of enteric nervous system in Hirschsprung's disease and intestinal neuronal dysplasia","volume":"28","author":"Geramizadeh","year":"2013","journal-title":"Histol Histopathol"},{"key":"R21-20251208","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4103\/0377-4929.81589","article-title":"Migration and maturation pattern of fetal enteric ganglia:A study of 16 cases","volume":"54","author":"Bandyopadhyay","year":"2011","journal-title":"Indian J Pathol Microbiol"},{"key":"R22-20251208","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0022-3468(67)80085-X","article-title":"Embryogenesis of intramural ganglia of the gut and its relation to Hirschsprung's disease","volume":"2","author":"Okamoto","journal-title":"J Pediatr Surg"},{"key":"R23-20251208","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1113\/jphysiol.2006.116814","article-title":"Interstitial cells of Cajal at the clinical and scientific interface","volume":"576","author":"Sanders","year":"2006","journal-title":"J Physiol"},{"key":"R24-20251208","first-page":"721","article-title":"Increased submucosal nerve trunk Caliber in aganglionosis:A \u201cpositive\u201dand objective finding in suction biopsies and segmental resections in Hirschsprung's disease","volume":"122","author":"Monforte-Mu\u00f1oz","year":"1998","journal-title":"Arch Pathol Lab Med"},{"key":"R25-20251208","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/modpathol.2017.4","article-title":"A critical appraisal of the morphological criteria for diagnosing intestinal neuronal dysplasia type B","volume":"30","author":"Terra","year":"2017","journal-title":"Mod Pathol"}],"container-title":["Indian Journal of Pathology and Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_574_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:20:25Z","timestamp":1787836825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_574_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/ijpm.ijpm_574_24","relation":{},"ISSN":["0377-4929","0974-5130"],"issn-type":[{"value":"0377-4929","type":"print"},{"value":"0974-5130","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"assertion":[{"value":"2024-07-10","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-16","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}