Neuroendocrine apendicopathy in morphologically normal appendices of patients with diagnosis of acute appendicitis: Diagnostic study

Abstract

Background: About 15%-25% of appendices removed to treat acute appendicitis present normal macro- and macroscopic morphology. The objective of this study was to verify an association of proinflammatory, neuroendocrine and immune mediators with morphologically normal appendices removed from patients with clinical laboratorial and imaging characteristics of acute appendicitis.

Materials and methods: Appendices removed from 121 adult patients of both genders were distributed into three groups according to their following characteristics: group 1: 53 macro- and microscopically normal appendices from patients with clinical, laboratorial and imaging diagnosis of acute appendicitis; group 2: 24 inflamed appendices from patients with clinical, laboratorial, imaging and histopathological diagnosis of acute appendicitis; group 3: 44 normal appendices from patients submitted to right colectomy to treat localized ascending colon adenocarcinoma. All appendices were immunohistochemically studied for gastrin inhibitor peptide, mast cell tryptase, vascular endothelial growth factor; intestinal vasoactive peptide, tumor necrosis factor alpha, interleukin 1, prostaglandin E2, gene-protein product 9.5, CD8 T lymphocytes, synaptophysine, enolase, and S100 protein.

Results: The group 1 revealed increased levels of synaptophysine, enolase, mast cell tryptase and PGP-9.5 comparing with the other two groups. The group 2 presented increased levels of interleukin 1, CD8 T lymphocytes and prostaglandin E2 comparing with the other two groups. The group 3 confirmed the normal levels of all these neuroendocrine, immune and proinflammatory mediators.

Conclusions: Morphologically normal appendices removed from patients with clinical and complementary exams indicating acute appendicitis have appendicular neuroimmunoendocrine disorder associated with the mediators synaptophysin, enolase, mast cell-related tryptase and gene-protein product 9.5.

Keywords: Appendicitis; CD8, CD8 T lymphocytes; Diagnosis; G1, group 1; G2, group 2; G3, group 3; GIP, gastrin inhibitor peptide; Histology; IL-1, interleukin 1; Immunohistochemistry; Neuroendocrine peptide; Neuroimmune peptide; PGE-2, prostaglandin E 2; PGP 9.5, gene-protein product 9.5; TNFα, tumor necrosis factor alpha; Tryptase, mast cell-related tryptase; VEGFA, vascular endothelial growth factor; VIP, intestinal vasoactive peptide.

Fig. 1

Microphotograph images showing positive mediators immunostaining (arrows) in the appendiceal wall (400 X):A - Synaptophysin in the submucosa nerve plexus and submucosa (SubM).B - Mast cell tryptase in the mucosa lamina propria (MucLP) (*).C - Enolase in myenteric nerve plexus, outer (OML) and inner (IML) muscle layer.D - PGP9.5 in the in myenteric nerve plexus.