Survival and Metastatic Lymph Node Patterns in Gastric Carcinoma with Exocrine and Neuroendocrine Components.

[BACKGROUND] Gastric carcinoma with coexisting exocrine and neuroendocrine components (GC-EN) is a rare and aggressive subtype of gastric cancer that presents unique challenges in diagnosis, treatment, and prognosis. The effect of lymph node metastasis with different components on survival in patients with GC-EN is unknown.

[PATIENTS AND METHODS] This retrospective study included 98 patients diagnosed with GC-EN at the China National Cancer Center between January 2004 and December 2020. GC-EN was classified into NEC-dominant, mixed adenoneuroendocrine carcinoma (MANEC), and AC-dominant based on the proportion of adenocarcinoma (AC) and neuroendocrine (NEC) components. Additionally, lymph nodes were categorized into NEC, AC, and MANEC types based on cellular composition.

[RESULTS] Of the 98 patients, 30 developed NEC-dominant type, 39 (39.8%) developed MANEC type, and 29 (29.6%) developed AC-dominant type. Additionally, 72.48% of the patients developed lymph node metastasis. The incidence rates of lymph node metastasis were significantly higher among patients with the NEC-dominant (76.6%, 23/30) and MANEC types (74.3%, 29/39) than among those with the ACC-dominant type (65.5%, 19/29; P < 0.05). Pathological T stage was a key factor influencing lymph node metastasis of NEC components in patients with GC-EN. Survival analysis revealed that lymph node metastasis significantly worsened the prognosis of patients with GC-EN (P < 0.05). Analysis of lymph node metastasis with different components on prognosis revealed that patients with GC-EN with lymph node metastasis of NEC components were associated with a significantly poorer prognosis than those without lymph node metastasis (hazard ratio 2.341, 95% confidence interval 1.125-4.871, P = 0.023), while patients with GC-EN with lymph node metastasis of MANEC and AC components exhibited no significant statistical differences. A new N staging system was developed on the basis of the number and different compositions of lymph node metastasis. The new N staging system demonstrated a higher C-index than the AJCC N staging system (0.739 vs. 0.719).

[CONCLUSIONS] Lymph node metastasis of NEC components is significantly associated with a poorer prognosis in patients with GC-EN. This study proposes a new N staging system that integrates lymph node count and components, potentially facilitating prognostic stratification and personalized treatment for patients with GC-EN.