Intramural ganglion structures in esophageal atresia: a morphologic and immunohistochemical study

Abstract

Introduction and Aim. Disorders of esophageal motility causing dysphagia and gastroesophageal reflux are frequent in survivors to esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The aim of the present study was to investigate the histologic and immunohistochemical features in both esophageal atretic segments to further understand the nature of the motor disorders observed in these patients. Material and Methods. Esophageal specimens from 12 newborns with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron sections that were stained with hematoxilin and eosin (H and E), and immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron-Specific-Enolase, Chromogranin A and Peripherin were evaluated under the microscope. Results. In controls, the distribution of the neural elements was rather homogenous at both levels of the esophagus. In contrast, the atretic segments showed quantitative and qualitative differences between them with sparser nervous tissue in the distal one in comparison with the proximal one and with controls. Conclusions. These results further support the assumption that histomorphological alterations of the muscular and nervous elements within the esophageal wall might contribute to esophageal dysmotility in patients surviving neonatal operations for EA/TEF.

Figure 1

Actin-A. (a) Control neonatal esophagus: Anti-A immunostaining marks strongly the muscularis mucosae (A), as well as both the inner (B) and outer (C) muscle layers; (b) Presence of disarranged and fragmented muscle bundles (A) reaching the epithelial basal line and segmental agenesia of muscularis mucosae. (B) Anti-A immunostaining is reduced in the smooth musle bundles of the UEP (c), but it is weaker in (d) the DES.

Figure 2

S-100 Protein (S-100). (a) The UEP shows fewer ganglion cells in the myenteric plexus (A) and an increased immunoreactivity for S-100 (B) than the control; (b) The DES shows few small immature cells (C) with less marked immunostaining than in the UEP.

Figure 3

Neurofilament (NF). A diffuse weak immunostaining expression is obvious at myoenteric site of both atretic esophageal segments. In some cases the NF immunoreactivity is absent in the DES.

Figure 4

Peripherin (P). Immunoreactivity is less marked in the myoenteric ganglion cells of (a) the UEP than in (b) the DES.

Figure 5

Neuron Specific Enolase (NSE). Weak cytoplasmic positivity in both proximal and distal segments.

Figure 6

Chromogranin A(CgA). Positive immunoreactivity is more marked in (a) the UEP than in (b) the DES.