Proportion of histologic component predicts lymph node metastasis risk in undifferentiated-type mucosal and submucosal gastric cancers

Undifferentiated-type (UD-type) gastric cancer is associated with a high frequency of lymph node metastasis (LNM); however, recent reports indicate that LNM frequency varies according to specific histologic components. We conducted a multicenter study to define criteria for distinguishing low- and high-risk histology groups for LNM in UD-type gastric cancers. Histologic components were classified into four types: poorly cohesive signet ring cells (SRC), poorly cohesive non-signet ring cells (non-SRCs), poorly differentiated tubular (PD), and differentiated-type (D-type). Their proportions were measured semi-quantitatively. The proportion of extracellular mucin (EMC) and the predominant histologic components within EMC were also recorded. LNM risk was analyzed based on pathological findings. Overall, 2256 mucosal and 688 submucosal UD-type cancers were analyzed. A higher SRC amount was linked to lower LNM frequency. Non-SRCs showed no association with LNM. Increased PD and D-type were linked to more frequent LNM; however, PD-predominant cases (PD ≥ 90%) showed paradoxically lower LNM frequency. SRC proportion > 10% was essential for low LNM probability. PD or D-type proportion > 10% is important for high LNM probability. Most compositions with low LNM probability (< 5%) showed a SRC majority (SRC > 50%) and ≤ 10% of PD or D-type. Pure poorly cohesive carcinomas with > 10% SRC and no PD or D-type were classified as low-risk histology (LNM probability 2.6%–3.4%). We developed a risk assessment method for tumor histology based on the composition of all histologic components and defined criteria to identify low-risk histology for LNM among UD-type cancers.