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.

The morphopathological particuliarities of intrinsic innervation of the esophagus in newborns with esophageal atresia and inferior tracheoesophageal fistula

“…Evaluation of anti-NF expression revealed a more dense, intrinsically fibrous esophageal fibrillation network in cases of esophageal atresia with inferior tracheoesophageal fistula, data similar to other studies [21]. At the same time some studies have described a diminished or even negative expression of this suggestive marker for diffuse neural diffusion [4,30].…”

“…Several immunohistochemical studies have found poor or negative immunoreactivity expression of neuronal markers, including neuron-specific enolase [16]. The anti-NSE 0 or 1+ expression found in some proximal areas of both atresied segments is characteristic of a neoglicogenesis deficiency [30].…”

“…Neurofilamentary proteins (NFPs) are intermediate filaments of neurons and their processes, believed to provide rigidity, traction resistance, and possibly guidance for intracellular transport in axons and dendrites. Given that NFP expression is determined exclusively in neurons, the NFP evaluation was used in the study to evaluate the presence of the mienterical plexus in the esophageal segments to detect neuroglial structures [17,30].…”

“…Chromogranin A (anti-CGA) is one of the major granines belonging to the family of acidic glycoproteins, which are a major component of the secretory granules of various endocrine and neuroendocrine cells of the classical endocrine glands and the diffuse neuroendocrine system, having multiple roles in the process of regulating neurotransmitters. The expression of chromogranin correlates with the amount of secretory vesicles in the neuroendocrine cells [12,30].…”

“…The primary motor disorders characteristic of esophageal atresia are the main cause of the abnormal development of muscular and nervous system (intrinsic and extrinsic innervation) of the esophagus, and these statements are supported in part by several histopathological studies [24]. Some authors believe that traumatic surgery can contribute to the esophageal dismotility in cases of eso phageal atresia due to a neurological defect caused by partial esophageal denervation [2], at the same time several studies found that abnormal innervation and neuromuscular defect of the esophagus are present before surgery [30]. Several authors have found the association of esophageal atresia with tracheoesophageal fistula with neural crest development malformations, where originates and innervation of the esophagus [21].…”