Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma.

Mucin occasionally accumulates intracellularly in colorectal mucinous adenocarcinomas, resulting in signet-ring cell morphology. In the current practice of pathology, there is no definitive rule on how to report a minor component of signet-ring cells in colorectal mucinous adenocarcinomas. We hypothesized that the absence of signet-ring cell component might have a favorable effect on survival of mucinous adenocarcinoma patients. To assess the biological characteristics of colorectal mucinous adenocarcinoma, we analyzed its clinicopathological features, microsatellite instability status, and survival outcomes and compared them with those of colorectal signet-ring cell carcinoma. A total of 266 consecutive colorectal mucinous adenocarcinoma patients and 65 signet-ring cell carcinoma patients were included. Mucinous adenocarcinomas, by comparison with signet-ring cell carcinomas, were characterized by development at an older age, less frequent vascular invasion and lymph node metastasis, and lower TNM stage at presentation. A total of 21 (22%) of 95 mucinous adenocarcinomas and 12 (19%) of 63 signet-ring cell carcinomas were high-frequency microsatellite instability. Patients with mucinous adenocarcinoma had significantly better survival than those with signet-ring cell carcinoma (P<0.0001) or than those with signet-ring cell carcinoma showing >50% extracellular mucin by volume (P<0.0001). In univariate analysis, absence of signet-ring cell component (P=0.0197), absence of vascular invasion, decreased invasion depth, no lymph node metastasis, and lower TNM stage had a favorable effect on survival of mucinous adenocarcinoma patients. Absence of vascular invasion, no lymph node metastasis, and lower TNM stage had a favorable effect on survival of signet-ring cell carcinoma patients. Multivariate analysis showed that higher TNM stage and T stage 4 were independent predictors of poor outcome in patients with mucinous adenocarcinoma. Our observations strongly suggest that pathologists should report the percentage of signet-ring cell component in colorectal mucinous adenocarcinomas and mucinous adenocarcinoma has different biologic behavior compared with signet-ring cell carcinoma.