Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm of the Esophagogastric Junction with Enteroblastic Differentiation and Morphologic-Immunophenotypic Discordance: A Case Report with Five-Year Disease-Free Survival.

INTRODUCTION: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the esophagogastric junction (EGJ) are extremely rare and are generally associated with aggressive clinical behavior. Enteroblastic (fetal gut-like) differentiation at this anatomical site is uncommon and is regarded as a poor prognostic feature. In addition, discordance between tumor morphology and immunophenotype in such mixed tumors has rarely been documented, and its clinical significance remains unclear. We report an exceptionally rare case of an EGJ MiNEN with enteroblastic differentiation and morphologic-immunophenotypic discordance that achieved long-term disease-free survival after surgery alone.

CASE PRESENTATION: An 81-year-old man presented with progressive dysphagia. Upper gastrointestinal endoscopy revealed a circumferential, ulcerated mass extending from the distal esophagus to the EGJ. Biopsy specimens suggested adenocarcinoma, and preoperative imaging demonstrated a localized EGJ tumor with suspected regional lymph node involvement. The patient underwent transhiatal distal esophagectomy with total gastrectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction. Histopathological examination of the resected specimen demonstrated a MiNEN, with each component accounting for more than 30% of the tumor volume. The glandular component consisted of a well-to-moderately differentiated adenocarcinoma with clear-cell morphology and enteroblastic features, showing positivity for glypican-3 and SALL4 with focal alpha-fetoprotein expression. The neuroendocrine component was a high-grade tumor with a markedly elevated proliferative index. Notably, immunophenotypic overlap was observed between the two components, with expression of neuroendocrine markers in the glandular areas and enteroblastic markers in the neuroendocrine nests. Resection margins were tumor-free. No adjuvant therapy was administered because of the patient's advanced age and comorbidities. The patient remains alive and disease-free 5 years after surgery.

CONCLUSIONS: This case illustrates an exceptionally rare MiNEN of the EGJ with enteroblastic differentiation and morphologic-immunophenotypic discordance. Despite the presence of aggressive histologic features, long-term disease-free survival was achieved with surgical resection alone. This report highlights the importance of thorough histopathological and immunohistochemical evaluation for accurate diagnosis and suggests that curative surgery alone may provide durable disease control in carefully selected patients with localized disease.