Differences in clinicopathology and prognosis between gastroesophageal junctional and gastric non-cardiac neuroendocrine carcinomas: a retrospective comparison study of consecutive 56 cases from a single institution in China

Gastric neuroendocrine carcinoma (NEC), including mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), is uncommon and differences in clinicopathological features and outcomes of NEC arising in various gastric regions remain elusive. We investigated 56 consecutive NECs identified among 3961 gastrectomies performed at our center between 2005 and 2021. We then compared clinicopathological characteristics and prognosis between gastroesophageal junctional (GEJ) NECs (N=39) and gastric non-cardiac NECs (N=17). No significant difference was found between the two groups in age, gender, tumor size, mixed non-neuroendocrine carcinoma component, MiNEN, NEC type, metastatic NEC component in lymph nodes, tumor infiltrating lymphocyte, lymph node metastasis, lymphovascular or perineural invasion, intestinal metaplasia in adjacent non-neoplastic mucosa, and expression of P53, PD-L1, TTF-1, HER2, and Ki-67. However, compared to gastric non-cardiac NECs, GEJ NECs displayed a significantly higher frequency of prevalence (2.79% versus 0.66%), pT3-T4 (92.3% versus 64.7%), advanced pathological stage (IIb-IV) (76.9% versus 47.1%), and a significantly lower 5-year overall survival rate (46.1% versus 73.1%) (P<0.05). The GEJ location was the only independent risk factor for overall survival. In stage-stratified comparisons, patients with stage II GEJ NEC demonstrated a significantly lower 5-year survival rate than those with gastric non-cardiac NEC at the same stage. Compared to non-NECs matched for age, gender, tumor location, and pathological summary stage, GEJ NEC was associated with significantly worse prognosis. In conclusion, GEJ NEC showed deeper invasion, more advanced pathological stages, and worse prognosis than gastric non-cardiac NEC. The findings provide pathologic evidence for individualized management strategies for patients with GEJ NEC. Future studies with larger samples are needed.