Intestinal neuronal dysplasia-like submucosal ganglion cell hyperplasia at the proximal margins of hirschsprung disease resections

Maya Swaminathan, Assaf P. Oron, Sumantra Chatterjee, Hannah Piper, Sandy Cope-Yokoyama, Aravinda Chakravarti, Raj P. Kapur

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Intestinal neuronal dysplasia type B (IND) denotes an increased proportion of hyperplastic submucosal ganglia, as resolved histochemically in 15-mm-thick frozen sections. IND has been reported proximal to the aganglionic segment in patients with Hirschsprung disease (HSCR) and is putatively associated with a higher rate of postsurgical dysmotility. We developed and validated histological criteria to diagnose IND-like submucosal ganglion cell hyperplasia (IND-SH) in paraffin sections and used the approach to study the incidence and clinical and/or genetic associations of IND-SH at the proximal margins of HSCR pull-through resection specimens. Full-circumference paraffin sections from the proximal margins of 64 HSCR colonic pull-through specimens and 24 autopsy controls were immunostained for neuron-specific Hu antigen, and nucleated ganglion cells in each submucosal ganglion were counted. In controls, an age-related decline in the relative abundance of "giant" ganglia (≥7 nucleated Hu-positive [Hu+] ganglion cells) was observed. A conservative diagnostic threshold for IND-SH (control mean ± 3× standard deviation) was derived from 15 controls less than 25 weeks of age. No control exceeded this threshold, whereas in the same age range, IND-SH was observed at the proximal margins in 15% (7 of 46) of HSCR resections, up to 15 cm proximal to the aganglionic segment. No significant correlation was observed between IND-SH and length of or distance from the aganglionic segment, sex, trisomy 21, RET or SEMA3C/D polymorphisms, or clinical outcome, but analysis of more patients, with better long-term follow-up will be required to clarify the significance of this histological phenotype.

Original languageEnglish (US)
Pages (from-to)466-476
Number of pages11
JournalPediatric and Developmental Pathology
Volume18
Issue number6
DOIs
StatePublished - Nov 1 2015

Fingerprint

Hirschsprung Disease
Ganglia
Hyperplasia
Paraffin
ELAV Proteins
Frozen Sections
Down Syndrome
Autopsy
Cohort Studies
Phenotype
Neurons

Keywords

  • Hirschsprung
  • Hyperganglionosis
  • Neuronal dysplasia
  • Observer bias
  • Transition zone

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

Cite this

Intestinal neuronal dysplasia-like submucosal ganglion cell hyperplasia at the proximal margins of hirschsprung disease resections. / Swaminathan, Maya; Oron, Assaf P.; Chatterjee, Sumantra; Piper, Hannah; Cope-Yokoyama, Sandy; Chakravarti, Aravinda; Kapur, Raj P.

In: Pediatric and Developmental Pathology, Vol. 18, No. 6, 01.11.2015, p. 466-476.

Research output: Contribution to journalArticle

Swaminathan, Maya ; Oron, Assaf P. ; Chatterjee, Sumantra ; Piper, Hannah ; Cope-Yokoyama, Sandy ; Chakravarti, Aravinda ; Kapur, Raj P. / Intestinal neuronal dysplasia-like submucosal ganglion cell hyperplasia at the proximal margins of hirschsprung disease resections. In: Pediatric and Developmental Pathology. 2015 ; Vol. 18, No. 6. pp. 466-476.
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AU - Oron, Assaf P.

AU - Chatterjee, Sumantra

AU - Piper, Hannah

AU - Cope-Yokoyama, Sandy

AU - Chakravarti, Aravinda

AU - Kapur, Raj P.

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KW - Observer bias

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