Surgical pathology of adenocarcinomas arising around or within the gastroesophageal junction

Classification of adenocarcinomas (AC) arising around or within the gastroesophageal junction (GEJ) is hampered by major morphologic and phenotypic overlaps. We reviewed the surgical pathology of esophagectomy specimens of 115 primary resected AC of the esophagus as defined by the 5th edition of the WHO classification regarding the anatomical site of the tumor, with corresponding categorization according to the Siewert AEG Classification and the preceding 4th edition of the WHO (discriminating esophageal adenocarcinomas/EAC and adenocarcinomas of the gastroesophageal junction/AdGEJ), and further histology findings. In addition, immunohistochemistry (IHC) for CDX2, CK7, CK20, MUC2, MUC5AC and MUC6 was performed. Sixty-eight cases were Siewert AEG type I and 47 cases Siewert AEG type II. Out of the AEG I tumors, 26 were classified as AdGEJ. Regardless of the classification system, more proximally located tumors showed less aggressive behavior with lower rates of lymph node metastases, lymphatic, venous and perineural invasion, better histological differentiation (p < 0.05 each) and were more frequently associated with pre-neoplastic Barrett's mucosa (p < 0.001). Histologically, the tumors displayed intestinal morphology in the majority of cases. IHC showed non-conclusive patterns with a frequent CK7+/CK20+ immunophenotype in all tumors, but also a gastric MUC5AC+ and MUC6+ phenotype in some proximal tumors. In conclusion, histology of the tumors and IHC failed to distinguish reliably between more proximal and more distal tumors. The presence of Barrett's mucosa rather than location alone, however, may help to further differentiating adenocarcinomas arising in this region and may be indicative for a particular biologic type.