Abstract
The aim of this study was to review critically the diagnostic features of intestinal neuronal dysplasia type B (IND B). Over a period of 5 years colonic mucosal biopsies of 773 children with symptoms of chronic constipation were examined. Four biopsies taken 2–10 cm above the pectinate line were cut in serial sections and histochemical lactate dehydrogenase, succinate dehydrogenase, (SDH) and acetylcholinesterase (AChE) reactions performed. Presence of giant ganglia of the submucosal plexus, being characterized by more than seven nerve cells, established the diagnosis of IND B. Giant ganglia were found to be age-independent changes, while hyperplasia of the submucosal plexus, increase of AChE activity in nerve fibres of the lamina propria and low SDH activity in nerve cells proved to be age-dependent findings which disappear during the maturation of the enteric nervous system. Using these criteria IND B was diagnosed in 209 children. In 64 of these patients a combination of IND B and aganglionosis (Hirschsprung's disease) was found. IND B seems to be related to premature expression of laminin A during embryogenesis, resulting in premature nerve cell differentiation in the myenteric and submucosal plexus, which in turn blocks neuroblast colonization of the rectum. IND B, hypoganglionosis and aganglionosis, which are often combined, may therefore be considered to be different manifestations of the same developmental abnormality.
Similar content being viewed by others
References
Angrist M, Kauffman E, Slaugenhaupt SA, Matise TC, Puffenberger EG, Washington SS, Lipson A, Cass DT, Reyna T, Weeks DE (1993) A gene for Hirschsprung's disease (megacolon) in the pericentromeric region of human chromosome 10. Nat Genet 4:325–326
Baumgarten HG (1967) Über die Verteilung von Catecholaminen im Darm des Menschen. Z Zellforsch 83:133–146
Bertoni-Freddari C, Fattoretti P, Casoli T, Spagna C, Meier-Ruge W, Ulrich J (1993) Morphological plasticity of synaptic mitochondria during aging. Brain Res 628:193–200
Borchard F, Meier-Ruge W, Wiebecke B, Briner J, Müntefering H, Födisch HJ, Holschneider AM, Schmidt A, Enck P, Stolte M (1991) Innervationsstörungen des Dickdarms — Klassifikation und Diagnostik. Pathologe 12:171–174
Briner J, Oswald HW, Hirsig J, Lehner M (1986) intestinal neuronal dysplasia — clinical and histochemical findings and its association with Hirschsprung's disease. Z Kinderchir 41:282–286
Bussmann H, Roth H, Deimling O von, Nützenadel W (1990) Variabilität klinischer Symptome bei neuronaler intestinaler Dysplasie. Monatsschr Kinderheilkd 138:284–287
Cass DT, Zhang AL, Morthrope J (1992) Aganglionosis in rodents. J Pediatr Surg 27:351–356
Edery P, Lyonnet S, Mulligan LM, Pelet A, Dow E, Abel L, Holder S, Nihoul-Fekete C, Ponder BA, Munnich A (1994) Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature 367:319–320
Fadda B, Maier WA, Meier-Ruge W, Schärli A, Daum R (1983) Neuronale intestinal Dysplasia. Eine kritische 10-Jahres-Analyse klinischer und bioptischer Diagnostik. Z Kinderchir 381:303–311
Fadda B, Pistor G, Meier-Ruge W, Hofmann-von Kap-herr S, Müntefering H, Espinosa R (1987) Symptoms, diagnosis and therapy of intestinal neuronal dysplasia masked by Hirschsprung's disease. Pediatr Surg Int 2:76–80
Gershon MD, Tennyson VM (1991) Microenvironmental factors in the normal and abnormal development of the enteric nervous system. Progr Clin Biol Res 373:257–276
Gershon MD, Epstein ML, Hegstrand L (1980) Colonisation of the chick gut by progenitors of enteric serotonergic neurons: distribution, differentiation and maturation within the gut. Dev Biol 77:41–51
Gershon MD, Chalazonitis A, Rothman TP (1993) From neural crest bo bowel: Development of the enteric nervous system. J Neurobiol 24:199–214
Goerttler K (1932) Der konstruktive Bau der menschlichen Darmwand. Gegenbaurs Morphol Jahrb 69:329–379
Gullotta F, Straaten G (1977) Hirschsprungsche Krankheit mit gleichzeitiger Aganglionose und sogenannter neuronaler Kolondysplasie (Dysganglionosis colica). Z Kinderchir 20:42–49
Hamberger B, Norberg KA (1965) Studies on some systems of adrenergic synaptic terminals in the abdominal ganglia of the cat. Acta Physiol Scand 65:235–242
Hanimann B, Inderbitzin D, Briner J, Sacher P (1992) Clinical relevance of Hirschsprung-associated intestinal neuronal dysplasia (HANID). Eur J Pediatr Surg 2:147–149
Harms KH, Bertele-Harms RM (1990) Variationen der neuronalen intestinalen Dysplasie Typ B. Der Kinderarzt 21:348–352
Heitz PU, Komminoth P (1990) Biopsy diagnosis of Hirschsprung's disease and related disorders. Curr Top Pathol 59:257–275
Hess R, Scarpelli DG, Pearse AGE (1958) The cytochemical localization of oxidative enzymes. II. Pyridine nucleotide-linked dehydrogenase. J Biophys Biochem Cytol 4:753–760
Hinkel AS, Bender SW, Posselt HG, Meier-Ruge W, Störer B, Holschneider AM, Waag KL (1989) Biochemische Untersuchungen der Azetylcholinesterase (AChE) an Rektumbiopsien und Darmresektaten bei Morbus Hirschsprung (Abstract). Monatsschr Kinderheilkd 137:120
Holschneider AM (1982) Manometric diagnosis. In: Holschneider AM (ed) Hirschsprung's Disease. Hippokrates Verlag, Stuttgart, pp 72–86
Kapur RP, Yost C, Palmiter RD (1992) A transgenic model for studying development of the enteric nervous system in normal and aganglionic mice. Development 116:167–175
Karnovsky MJ, Roots L (1964) A “direct-coloring” thiocholine method for cholinesterase. J Histochem Cytochem 12:219–221
Kessler S, Campbell JR (1985) Neuronal colonic dysplasia associated with short-segment Hirschsprung's disease. Arch Pathol Lab Med 109:532–533
Koletzko S, Ballauff A, Hadziselimovic F, Enck P (1992) Anorectal manometry in Hirschsprung's disease and intestinal neuronal dysplasia. In: Hadziselimovic F, Herzog B (eds) Pediatric Gastroenterology: Inflammatory Bowel Diseases and Morbus Hirschsprung. Kluwer Academic Publishers, Dordrecht, pp 263–281
Krebs C, Silva MC, Parra MA (1991) Anorectal electromanometry in the diagnosis of intestinal neuronal dysplasia in childhood. Eur J Pediatr Surg 1:40–44
Lyonnet S, Bolino A, Pelet A, Abel L, Nihoul-Fekete C, Briard ML, Mok-Siu V, Kaariainen H, Martucciello G, Lerone M (1993) A gene for Hirschsprung's disease maps to the proximal long arm of chromosom 10. Nat Genet 4:346–350
Meier-Ruge W (1971) Über ein Erkrankungsbild des Colon mit Hirschsprung-Symptomatik. Verh Dtsch Ges Pathol 55:506–509
Meier-Ruge W (1974) Hirschsprung's disease: Its aetology, pathogenesis and differential diagnosis. Curr Top Pathol 59:131–179
Meier-Ruge W (1983) Zur Pathogenese anorektaler Anomalien und Dysganglionose. In: Hofmann-von Kap-herr S, Schärli A, Sauer H, Enger E (eds) Anorektale Fehlbildungen. Gustav Fischer, Stuttgart, pp 19–22
Meier-Ruge W (1985) Angeborene Dysganglionosen des Colon. Der Kinderarzt 16:151–164
Meier-Ruge W (1990) Das morphologische Erscheinungsbild der neuronalen Dysplasie des Plexus submucosus. Der Kinderarzt 21:837–844
Meier-Ruge W (1992) Epidemiology of congenital innervation defects of the distal colon. Virchows Arch [A] 420:171–177
Meier-Ruge W, Hunziker O, Tobler HJ, Walliser C (1972) The pathophysiology of aganglionosis of the entire colon (Zuelzer-Wilson Syndrome). Morphometric investigations of the extent of sacral parasympathetic innervation of the circular muscle of the aganglionic colon. Beitr Pathol 147:228–236
Meier-Ruge W, Käufeler RE, Brönnimann P (1992) Classification of inborn malformation of distal gut innervation. In: Hadziselimovic F, Herzog B (eds) Pediatric Gastroenterology: Inflammatory Bowel Disease and Morbus Hirschsprung. Academic Publishers, Dordrecht, pp 177–201
Meijers JHC, Sanden MP van der, Tibboel D, Kamp AWM van der, Luider TM, Molenaar JC (1992) Colonization characteristics of enteric neural crest cells: embryological aspects of Hirschsprung's disease. J Pediatr Surg 27:811–814
Moore SW, Rode H, Millar AJW, Albertyn R, Cywes S (1991) Familial aspects of Hirschsprung's disease. Eur J Pediatr Surg 1:57–100
Moore SW, Kaschula ROC, Cywes S (1993) Familian and genetic aspects of intestinal neuronal dysplasia and Hirschsprung's disease. Pediatr Surg Int 8:406–409
Munakata K, Morita K, Okabe I, Seuoka H (1985) Clinical and histological studies of neuronal dysplasia. J Pediatr Surg 20:231–235
Nachlas MM, Tsou KC, Souza E, Cheng CS, Seligman AM (1957) Cytochemical demonstration of succinic dehydrogenase by the use of a new p-nitrophenyl substituted ditetrazole. J Histochem Cytochem 5:420–436
Norberg KA (1964) Adrenergic innervation of the intestinal wall studied by fluorescence microscopy. Int J Neuropharmacol 3:379–382
Norberg KA (1967) Transmitter histochemistry of the sympathetic adrenergic nervous system. Brain Res 5:125–170
Okamoto E, Ueda T (1967) Embryogenesis of intramural ganglia of the gut and its relation to Hirschsprung's disease. J Pediatr Surg 2:437–443
Parikh DH, Tam PKH, Lloyd DA, Velzen D van, Edgar DH (1992) Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung's disease. J Pediatr Surg 27:991–996
Pistor G (1989) Functional colonic ultrasonography: normal findings of colonic motility and follow-up in intestinal neuronal dysplasia. Prog Pediatr Surg 24:155–164
Pistor G (1990) Die Colonsonographie als bildgebender Verlaufsparameter bei neuronaler Dysplasie. Der Kinderarzt 21:182–186
Pistor G, Hofmann-von Kap-herr S, Grüssner R, Munakata K, Müntefering H (1987) intestinal neuronal dysplasia — Modern diagnosis and therapy. Pediatr Surg Int 2:352–358
Puri P, Lake BD, Nixon HH, Mishalany H, Claireaux AE (1977) Neuronal colon dysplasia: an unusual association of Hirschsprung's disease. J Pediatr Surg 12:681–685
Rintala R, Rapola J, Louhimo I (1989) intestinal neuronal dysplasia. Prog Pediatr Surg 24:186–192
Romeo G, Ronchetto P, Luo Y, Barone V, Seri M, Ceccherini J, Pasini B, Bocciardi R, Lesone M, Kaariainen H (1994) Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature 367:377–378
Sacher P, Briner J, Stauffer UG (1991) Unusual cases of intestinal neuronal dysplasia. Pediatr Surg Int 6:225–226
Schärli AF (1992) intestinal neuronal dysplasia. Pediatr Surg Int 7:2–7
Schärli AF (1992) Surgery for Hirschsprung's disease and intestinal neuronal dysplasia. In: Hadziselimovic F, Herzog B (eds) Pediatric Gastroenterology: Inflammatory Bowel Disease and Morbus Hirschsprung. Kluwer Academic Publishers, Dordrecht, pp 287–296
Schärli AF, Meier-Ruge W (1981) Localized and disseminated forms of intestinal neuronal dysplasia mimicking Hirschsprung's disease. J Pediatr Surg 16:164–170
Schofield DE, Yunis EJ (1991) Intestinal neuronal dysplasia. J Pediatr Gastroenterol Nutr 12:182–189
Schofield DE, Yunis EJ (1992) What is intestinal neuronal dysplasia? Pathol Ann 27:249–262
Simpser E, Kahn E, Kenigsberg K, Duffy L, Markowitz J, Daum F (1991) intestinal neuronal dysplasia: quantitative diagnostic criteria and clinical management. J Pediatr Gastroenterol Nutr 12:61–64
Smith VV (1992) Isolated intestinal neuronal dysplasia: a descriptive histological pattern of a distinct clinicopathological entity? In: Hadziselimovic F, Herzog B (eds) Pediatric Gastroenterology: Inflammatory Bowel Diseases and Morbus Hirschsprung. Kluwer Academic Publishers, Dordrecht, 203–213
Stoss F (1990) Neuronal dysplasia. Consideration of the pathogenesis and treatment of primary chronic constipation in adults. Int J Colorectal Dis 5:106–112
Stoss F, Meier-Ruge W (1991) Diagnosis of neuronal colon dysplasia in primary chronic constipation and sigmoid diverticulosis — endoscopic biopsy and enzyme-histochemical examination. Surg Endosc 5:146–149
Wiebecke B, Müller-Lissner S (1990) Neuronale intestinale Dysplasie (IND) Typ B beim Erwachsenen. Verh Dtsch Ges Pathol 74:525
Wolgemuth DJ, Behringer RR, Mostoller MP, Brinster RL, Palmiter RD (1989) Transgenic mice overexpressing the mouse homeobox-containing gene Hox-1,4 exhibit abnormal gut development. Nature 337:466–467
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Meier-Ruge, W., Brönnimann, P., Gambazzi, F. et al. Histopathological criteria for intestinal neuronal dysplasia of the submucosal plexus (type B). Vichows Archiv A Pathol Anat 426, 549–556 (1995). https://doi.org/10.1007/BF00192108
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00192108