Gastric Dysplasia-Like Epithelial Atypia Associated with Chemoradiotherapy for Esophageal Cancer: A Clinicopathologic and Immunohistochemical Study of 15 Cases

Abstract

Preoperative chemotherapy combined with radiotherapy (chemrad) is a common type of neoadjuvant treatment for esophageal adenocarcinoma or squamous cell carcinoma. The purpose of this study was to describe the clinical, histologic, proliferative (MIB-1), and oncogenetic (p53) features of 15 patients with gastric dysplasia-like epithelial atypical changes associated with preoperative chemrad for esophageal cancer. Two of these cases were initially misinterpreted as dysplasia, which led to partial gastrectomy. The findings were compared with 12 age-and sex-matched patients with known gastric dysplasia. Cases with gastric dysplasia-like epithelial atypia were significantly associated with a flat gross appearance, a patchy distribution, foveolar and gland involvement, surface maturation, an open nuclear chromatin pattern with prominent nucleoli, retention of nuclear polarity, mitoses confined to the pits, lack of atypical mitoses, cytoplasmic hypereosinophila and/or vacuolization, a lack of association with intestinal metaplasia, and finally, irregular glandular microcystic change, in comparison to the dysplasia controls. Furthermore, the study cases showed MIB-1 positivity restricted to the deep foveolar epithelium and an absence of p53 staining in 14 of 15 cases, in contrast to the dysplasia controls, in which MIB-1 stained both the deep and superficial foveolar epithelium and surface epithelium, and p53 was positive in all cases (100%). In summary, a number of histologic and immunohistochemical features may distinguish gastric dysplasia-like epithelial atypia associated with chemrad for esophageal cancer from true dysplasia. Pathologists should be aware of this entity and its histologic and immunohistochemical features to avoid misinterpretation and prevent unnecessary treatment.

Histomorphometry and immunohistochemical features of grade I (WHO) oral radiomucositis

“…In several instances, the dysplasia-like changes were misinterpreted as neoplastic, which in retrospect led to unnecessary treatment. Similar diagnosis difficulties can be found between dysplasia-like induced by radiation and true dysplasia in the esophagus (Brien et al, 2001). Inflammatory mononuclear infiltrate found in our cases was similar to that described by Etiz et al (2000) and Handschel et al (2001b).…”

“…Cellular pleomorphism, hyperchromatism, eosinophilia, vacuolization, enlarged nuclei and an increased nuclear/ cytoplasmic ratio were observed in atypical cells in our study. Evaluation of the esophageal cells after chemoradiotherapy revealed 7.5% of cases with dysplasia-like epithelial atypia, with similar histomorphology like our atypical cells (Brien et al, 2001). In this report, dysplasia-like cases were less positive for p53 and MIB1 than true dysplasia.…”

“…In several instances, the dysplasia‐like changes were misinterpreted as neoplastic, which in retrospect led to unnecessary treatment. Similar diagnosis difficulties can be found between dysplasia‐like induced by radiation and true dysplasia in the esophagus (Brien et al , 2001).…”

“…Our data confirm an increased level of p53 in the irradiated tissue and its possible association with apoptotic death across the epithelium during the RxT sequence (Sonis, 1998; Jee et al , 2005). The p53 staining was not a differential between dysplastic‐like and true dysplasia demonstrated by Brien et al (2001), maybe because of not similar expression behavior in the mucosal sites and the therapeutic approachment, which included chemotherapy.…”

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

“…However focal glandular atrophy, epithelial attenuation and apoptosis have been described within the specialised gastric mucosa,8 and Brien and colleagues noted that radiation induced atypia within benign glands can mimic dysplasia or even residual carcinoma 18. Similar epithelial changes together with crypt architectural distortion and fibrosis within the lamina propria and submucosa have been described in treated rectal tumours 19 20.…”