Signet Ring Cell Esophageal Adenocarcinoma: A Rare Histologic Variant

Abstract

A 68-year-old man with a history of heavy smoking presented with 3 weeks of dysphagia to solids. Endoscopy revealed erythema in the lower esophagus with scattered white plaques covering umbilicated nodules (Figure A); on gastric retroflexion, these lesions extended beyond the esophagogastric junction (Figure B). Infectious esophagitis, specifically esophageal candidiasis or herpes esophagitis, was suspected, but surprisingly the biopsies revealed squamous mucosa with infiltrating adenocarcinoma containing copious signet ring cells (SRC) (Figure C: low [left] and high [right] magnification; arrows indicate SRC with large intracellular mucin-containing vacuoles displacing nuclei to the cell periphery). SRC comprised >50% of the tumor mass. Immunostaining detected overexpressed programmed death-ligand-1 (PD-L1) but not human epidermal growth factor receptor-2 (HER-2). Positron emission tomography/computed tomography revealed distal esophageal wall thickening with mild metabolic uptake but no enlarged, metabolically active lymph nodes. Endoscopic-ultrasonography revealed an irregular circumferential mucosal mass extending 36 cm from the incisors to 1 cm distal to the esophagogastric junction, invading the adventitia but not regional lymph nodes (Figure D). The cancer progressed despite neoadjuvant chemoradiotherapy, esophagectomy, and adjuvant immunotherapy; the patient died 8 months after presentation. SRC adenocarcinoma accounts for <10% of esophageal adenocarcinomas and portends a worse outcome. Clearly, the presence of esophageal skip lesions should not exclude the possibility of neoplasia. The prevalence and prognostic value of PD-L1 and HER-2 overexpression in esophageal SRC adenocarcinoma are unknown.