Mucosal endocrine cell micronests and single endocrine cells following neo-adjuvant therapy for adenocarcinoma of the distal oesophagus and oesophagogastric junction

Abstract

Aims: To determine the frequency of endocrine cell micronests (ECM) and single endocrine cells (SEC) within the glandular mucosa of the distal oesophagus and oesophagogastric junction (OGJ) following neo-adjuvant therapy for adenocarcinoma. Methods: The resection specimens from 11 patients with adenocarcinoma of the distal oesophagus or OGJ who had undergone preoperative chemotherapy or chemoradiotherapy (CRT) were reviewed and stained immunohistochemically for cytokeratin and chromogranin. The presence of ECM and/or SEC within the mucosa adjacent to the tumour was noted, and the results correlated with the extent of tumour regression. The corresponding pretreatment endoscopic biopsy specimens were reviewed in 6 cases, and the results were also compared to 10 tumour resections from patients with no history of neo-adjuvant treatment. Results: ECM and/or SEC were identified in 8/11 resection specimens after chemotherapy or CRT. The endocrine cells were typically located within the deep lamina propria or muscularis mucosae and were associated with varying degrees of glandular atrophy and inflammation. The appearances were most consistent with endocrine cell preservation (pseudo-hyperplasia) following treatment. Isolated endocrine elements were not seen in the pretreatment biopsy specimens, while rare SEC without ECM were identified in only 2/10 control resection specimens. Conclusions: Endocrine cell pseudo-hyperplasia may be seen within atrophic glandular mucosa following neo-adjuvant therapy of distal oesophageal/OGJ adenocarcinomas. The changes are analogous to those seen in chronic atrophic gastritis and should not be misinterpreted as those of residual tumour.

Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study

“…In support of this observation, no endocrine cells increase was observed in the non-neoplastic irradiated mucosa in PLRT cases, in which acute radiation colitis features were characteristically absent. Unlike previous reports [ 21 ], which found the extent of endocrine differentiation within the tumor to be proportional to the degree of tumor regression, we did not observe increase in endocrine cells within the tumor in either group of patients.…”

“…An increase in endocrine cells was noted in the irradiated non-neoplastic mucosa in the PSRT group. In analogy to previous observations in esophageal adenocarcinoma after neo-adjuvant treatment [ 21 ], we interpreted the endocrine cells as residual normal endocrine elements, appearing more conspicuous for the radiation-induced glandular damage causing “passive clustering” [ 22 ]. In support of this observation, no endocrine cells increase was observed in the non-neoplastic irradiated mucosa in PLRT cases, in which acute radiation colitis features were characteristically absent.…”

Aberrant p53 Expression in Gastric Biopsies and Resection Specimens Following Neoadjuvant Chemoradiation: A Diagnostic Pitfall

“…Features of therapy-related epithelial changes included nuclear changes (pseudostratification, hyperchromasia, nucleomegaly, anisonucleosis, and prominent nucleoli), increased mitoses, cytoplasmic mucin depletion, hypereosinophilia, or clear cell changes, glandular atrophy, and/or irregular microcystic change as previously described by Brien et al 7 The presence or absence of neuroendocrine cell micronests, defined as scattered, non-confluent clusters of 5 to 15 neuroendocrine cells in the lamina propria or muscularis mucosae was also noted. 13, 14…”

Updates in staging and pathologic evaluation of esophageal carcinoma following neoadjuvant therapy

“…One 19 while other studies failed to show any impact on patient outcomes. 17,20,21 More studies are needed to clarify the significance of residual neuroendocrine cells in esophageal ACs (EACs) following neoadjuvant therapy. Nodal status remains prognostically important in EC patients, even after neoadjuvant chemotherapy.…”

“…However, the significance of these neuroendocrine cells in the esophagus remains controversial. One study showed worse clinical outcome associated with residual neuroendocrine cells, 19 while other studies failed to show any impact on patient outcomes 17,20,21 . More studies are needed to clarify the significance of residual neuroendocrine cells in esophageal ACs (EACs) following neoadjuvant therapy.…”