Microsatellite unstable esophageal adenocarcinoma masquerading as a conventional esophageal primary

Abstract

Abstract Introduction/Objective Patients with microsatellite instability (MSI) are susceptible to developing epithelial malignancies in multiple organs and systems, especially along the gastrointestinal tract. It’s important to know that MSI-tumors may present with an intriguing non-classical, “non-MSI-appearing”, histomorphology that deviates from the well-known MSI or Lynch syndrome spectrum. Pathologists should thus be prepared for unusual histopathological presentations in order to detect MSI and related therapeutic and prognostic targets. Ultimately, a timely and accurate classification is a crucial step in guiding clinical course. Methods/Case Report An 80-year-old male presented to an outside facility due to worsening dysphagia. Imaging and endoscopy studies confirmed a near-obstructing distal esophageal mass. Subsequently, an esophagogastrostomy was performed, which removed a moderately differentiated adenocarcinoma (pT3N1). The patient was managed with conventional chemotherapy after the surgery; however, due to progressive metastasis involving the liver, he was referred to our cancer center. Results (if a Case Study enter NA) Upon review of outside pathology materials, the tumor displayed irregularly arranged bizarre glands with eosinophilic cytoplasm and unusually large nuclei within the abundant fibrotic stroma. No intra-tumoral lymphocytes or “Crohn’s-like” pushing borders were identified. However, ancillary tests performed on acquired outside material showed loss of MLH1 and PMS2 with retained MSH2 and MSH6 in the tumor. Subsequent mutational analysis revealed additional MSI-related carcinogenic mutations. Accordingly, the previous regimen was switched to immunotherapy-based management. The patient remains disease-free 10-months later. Conclusion This unusual MSI esophageal adenocarcinoma exemplifies that such tumors may present with non- MSI/non-lynch histomorphology and that ancillary analyses should be carried out without reservation to evaluate microsatellite status. Thus, optimizing patient management and outcome.