Advertisement

Virchows Archiv

, Volume 470, Issue 6, pp 679–685 | Cite as

Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis

  • Koichiro YoshimaruEmail author
  • Tomoaki Taguchi
  • Satoshi Obata
  • Junkichi Takemoto
  • Yoshiaki Takahashi
  • Tsuyoshi Iwanaka
  • Yusuke Yanagi
  • Masaaki Kuda
  • Kina Miyoshi
  • Toshiharu Matsuura
  • Yoshiaki Kinoshita
  • Takako Yoshioka
  • Atsuko Nakazawa
  • Yoshinao Oda
Original Article

Abstract

Isolated hypoganglionosis (IHG) has been proposed as a distinct entity with two subtypes: congenital IHG (CIHG) and acquired IHG (AIHG). However, due to the rarity of the disease and the lack of defining histological criteria, the concept of IHG is not widely accepted. We studied paraffin-embedded intestinal specimens from 79 patients diagnosed with Hirschsprung’s disease (HD) (n = 49), CIHG (n = 25), and AIHG (n = 5) collected between January 1996 and December 2015. Histopathological diagnosis of HD, CIHG, and AIHG was confirmed by hematoxylin and eosin staining and immunohistochemical staining using Hu C/D and CD56. We evaluated (immuno)histopathological findings, counted the number of ganglion cells, and measured the size of Auerbach’s plexus. Hu C/D labeled neuronal cell bodies, whereas CD56 was detected in all neuronal components. In HD, all ganglion cells in Auerbach’s plexus in the normoganglionic segment (NGS) were immunoreactive for Hu C/D, whereas in the aganglionic segment (AGS), these were replaced by CD56-positive extrinsic nerve fibers and bundles. The number of ganglion cells in AIHG and CIHG was significantly lower than in the NGS of HD (p < 0.05). Auerbach’s plexus was significantly smaller in CIHG (p < 0.05) but in AIHG equivalent to the NGS in HD. In summary, immunostaining for Hu C/D and CD56 is useful for definitive histopathological diagnosis of IHG.

Keywords

Acquired isolated hypoganglionosis Allied disorders of Hirschsprung’s disease CD56 Congenital isolated hypoganglionosis Hu C/D Immunohistochemistry 

Abbreviations

HD

Hirschsprung’s disease

ADHD

allied disorders of Hirschsprung’s disease

IHG

isolated hypoganglionosis

CIHG

congenital isolated hypoganglionosis

AIHG

acquired isolated hypoganglionosis

HE

hematoxylin and eosin

NGS

normoganglionic segment

AGS

aganglionic segment

Notes

Acknowledgements

The authors thank Brian Quinn (Editor-in-Chief, Japan Medical Communication Inc., Fukuoka, Japan) for his assistance with reading and editing the manuscript and Dr. Shimozono, Dr. Uchida, Dr. Nakahara, Dr. Muraji, and Dr. Ishii for giving the authors the chance to evaluate the histological slides.

Author contributions

KY and TT participated in the design, data analysis, research, and writing of the manuscript; SO and JT participated in the data analysis and research; YT, TI, YY, MK, KM, TM, YK, TY, AN, and YO participated in the data analysis and provided helpful advices.

Compliance with ethical standards

This retrospective study was performed in accordance with the Ethical Guidelines for Clinical Research published by the Ministry of Health, Labor, and Welfare of Japan on July 30, 2003 (revised in 2008) and complied with the Declaration of Helsinki (revised in 2008). All parents or guardians of patients in this study gave informed consent prior to the operation. This study was approved by the ethics committee for clinical research of Kyushu University Hospital (No.28-155).

Funding

This study was funded by a grant from The Ministry of Health, Labor Sciences Research Grants for Research on intractable disease (H23-042, H24-037, H26-045).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2017_2128_MOESM1_ESM.pdf (23 kb)
ESM 1 (PDF 22 kb)
428_2017_2128_MOESM2_ESM.pdf (13 kb)
ESM 2 (PDF 13 kb)

References

  1. 1.
    Wetherill C, Sutcliffe J (2014) Hirschsprung disease and anorectal malformation. Early Hum Dev 90:927–932CrossRefPubMedGoogle Scholar
  2. 2.
    Langer JC (2013) Hirschsprung disease. Curr Opin Pediatr 25:368–374CrossRefPubMedGoogle Scholar
  3. 3.
    Martucciello G, Pini Prato A, Puri P et al (2005) Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: a report from the fourth international symposium on Hirschsprung's disease and related neurocristopathies. J Pediatr Surg 40:1527–1531CrossRefPubMedGoogle Scholar
  4. 4.
    Taguchi T, Ieiri S, Miyoshi K et al (2017) The incidence and outcome of allied disorders of Hirschsprung's disease in Japan: results from a nationwide survey. Asian J Surg 40:29–34CrossRefPubMedGoogle Scholar
  5. 5.
    Taguchi T, Masumoto K, Ieiri S, Nakatsuji T, Akiyoshi J (2006) New classification of hypoganglionosis: congenital and acquired hypoganglionosis. J Pediatr Surg 41:2046–2051CrossRefPubMedGoogle Scholar
  6. 6.
    Watanabe Y, Kanamori Y, Uchida K, Taguchi T (2013) Isolated hypoganglionosis: results of a nationwide survey in Japan. Pediatr Surg Int 29:1127–1130CrossRefPubMedGoogle Scholar
  7. 7.
    Swaminathan M, Kapur RP (2010) Counting myenteric ganglion cells in histologic sections: an empirical approach. Hum Pathol 41:1097–1108CrossRefPubMedGoogle Scholar
  8. 8.
    Park SH, Min H, Chi JG, Park KW, Yang HR, Seo JK (2005) Immunohistochemical studies of pediatric intestinal pseudo-obstruction: bcl2, a valuable biomarker to detect immature enteric ganglion cells. Am J Surg Pathol 29:1017–1024PubMedGoogle Scholar
  9. 9.
    Dingemann J, Puri P (2010) Isolated hypoganglionosis: systematic review of a rare intestinal innervation defect. Pediatr Surg Int 26:1111–1115CrossRefPubMedGoogle Scholar
  10. 10.
    Geramizadeh B, Akbarzadeh E, Izadi B, Foroutan HR, Heidari T (2013) Immunohistochemical study of enteric nervous system in Hirschsprung's disease and intestinal neuronal dysplasia. Histol Histopathol 28:345–351PubMedGoogle Scholar
  11. 11.
    Desmet AS, Cirillo C, Vanden Berghe P (2014) Distinct subcellular localization of the neuronal marker HuC/D reveals hypoxia-induced damage in enteric neurons. Neurogastroenterol Motil 26:1131–1143CrossRefPubMedGoogle Scholar
  12. 12.
    Phillips RJ, Hargrave SL, Rhodes BS, Zopf DA, Powley TL (2004) Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers. J Neurosci Methods 133:99–107CrossRefPubMedGoogle Scholar
  13. 13.
    Oh JT, Han AR, Yang WI, Han SJ, Choi SH, Hwang EH (2002) Morphometric evaluation of PGP9.5 and NCAM expressing nerve fibers in colonic muscle of patients with Hirschsprung's disease. Yonsei Med J 43:31–36CrossRefPubMedGoogle Scholar
  14. 14.
    Giles AP, Casaclang D, Keen CE (1998) Diagnosis of Hirschsprung's disease. Pediatr Dev Pathol 1:571–572CrossRefPubMedGoogle Scholar
  15. 15.
    Meier-Ruge W, Bruder E (2008) Histopathological diagnosis and differential diagnosis of Hirschsprung’s disease. In: Holschneider AM, Prem P (eds) Hirschsprung’s disease and allied disorders. Springer, Berlin, Heidelberg, pp 185–197CrossRefGoogle Scholar
  16. 16.
    Meier-Ruge WA, Brunner LA, Engert J et al (1999) A correlative morphometric and clinical investigation of hypoganglionosis of the colon in children. Eur J Pediatr Surg 9:67–74CrossRefPubMedGoogle Scholar
  17. 17.
    Munakata K, Fukuzawa M, Nemoto N (2002) Histologic criteria for the diagnosis of allied diseases of Hirschsprung's disease in adults. Eur J Pediatr Surg 12:186–191CrossRefPubMedGoogle Scholar
  18. 18.
    Meier-Ruge W, Morger R, Rehbein F (1970) The hypoganglionated megacolon as accompanying disease of Hirschsprung’s disease. Z Kinderchir 8:254–264Google Scholar
  19. 19.
    Tiffin ME, Chandler LR, Faber HK (1940) Localized absence of the ganglion cell of myenteric plexus in congenital megacolon. Am J Dis Child 59:1071–1082Google Scholar
  20. 20.
    Holland-Cunz S, Göppl M, Rauch U, Bär C, Klotz M, Schäfer KH (2006) Acquired intestinal aganglionosis after a lytic infection with varicella-zoster virus. J Pediatr Surg 41:e29–e31CrossRefPubMedGoogle Scholar
  21. 21.
    Iantorno G, Bassotti G, Kogan Z et al (2007) The enteric nervous system in chagasic and idiopathic megacolon. Am J Surg Pathol 31:460–468CrossRefPubMedGoogle Scholar
  22. 22.
    Dajani OM, Slim MS, Mansour A (1986) Acquired hypoganglionosis after soave endorectal pull-through procedure—a case report. Z Kinderchir 41:248–249PubMedGoogle Scholar
  23. 23.
    Wedel T, Roblick U, Gleiss J et al (1999) Disorders of intestinal innervation as a possible cause for chronic constipation. Zentralbl Chir 124:796–803PubMedGoogle Scholar
  24. 24.
    Cho K-M, Lim S-U, Park S-Y, Lee K-H, Jae-Kyun J, Rew J-S (2015) A case of colonic hypoganglionosis complicated with colonic ulcers. Soonchunhyang Med Sci 21:36–39CrossRefGoogle Scholar
  25. 25.
    Kapur RP (2014) Intestinal motor disorder. In: Russo P, Ruchelli ED, Piccoli DA (eds) Pathology of pediatric gastrointestinal and liver disease. Springer, Berlin, Heidelberg, pp 249–316Google Scholar
  26. 26.
    Taguchi T, Tanaka K, Ikeda K (1985) Fibromascular dysplasia of arteries in Hirschsprung’s disease. Gastroenterology 88:1099–1103CrossRefPubMedGoogle Scholar
  27. 27.
    Lin Z, Gao N, Hu HZ et al (2002) Immunoreactivity of Hu proteins facilitates identification of myenteric neurones in guinea-pig small intestine. Neurogastroenterol Motil 14:197–204CrossRefPubMedGoogle Scholar
  28. 28.
    Wakamatsu Y, Weston JA (1997) Sequential expression and role of Hu RNA-binding proteins during neurogenesis. Development 124:3449–3460PubMedGoogle Scholar
  29. 29.
    Nogueira A, Campos M, Soares-Oliveira M et al (2001) Histochemical and immunohistochemical study of the intrinsic innervation in colonic dysganglionosis. Pediatr Surg Int 17:144–151CrossRefPubMedGoogle Scholar
  30. 30.
    Amiot A, Cazals-Hatem D, Joly F et al (2009) The role of immunohistochemistry in idiopathic chronic intestinal pseudoobstruction (CIPO): a case-control study. Am J Surg Pathol 33:749–758CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Koichiro Yoshimaru
    • 1
    Email author return OK on get
  • Tomoaki Taguchi
    • 1
  • Satoshi Obata
    • 1
  • Junkichi Takemoto
    • 1
  • Yoshiaki Takahashi
    • 1
  • Tsuyoshi Iwanaka
    • 1
  • Yusuke Yanagi
    • 1
  • Masaaki Kuda
    • 1
  • Kina Miyoshi
    • 1
  • Toshiharu Matsuura
    • 1
  • Yoshiaki Kinoshita
    • 1
  • Takako Yoshioka
    • 2
  • Atsuko Nakazawa
    • 2
  • Yoshinao Oda
    • 3
  1. 1.Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical SciencesKyushu UniversityHigashi-kuJapan
  2. 2.Department of PathologyNational Center for Child Health and DevelopmentSetagayaJapan
  3. 3.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Personalised recommendations