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


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.


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



Hirschsprung’s disease


allied disorders of Hirschsprung’s disease


isolated hypoganglionosis


congenital isolated hypoganglionosis


acquired isolated hypoganglionosis


hematoxylin and eosin


normoganglionic segment


aganglionic segment



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).


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)


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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

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