Epidemiology of Signet Ring Cell Adenocarcinomas

Signet ring cell adenocarcinomas (SRCCs) are a rare histological subtype of adenocarcinomas with a poor prognosis, typically due to advanced disease at diagnosis. A signet ring cell, mimicking its moniker, contains abundant intracytoplasmic mucin that pushes the nucleus to the periphery. In these cancers, this cell feature comprises more than 50% of the tumor. Despite predilection for the gastrointestinal tract, and in particular the stomach, primary SRCCs are also described in other sites, typically in case reports. This literature, however, lacks a standardized overview of the SRCC disease entity. Using a retrospective cohort approach, we summarize the clinicodemographic and mortality outcomes of SRCCs in thirteen primary sites, comprising 95% of all SRCCs in the Surveillance, Epidemiology, and End Results Program (SEER), a population-level cancer database covering nearly one-third of the United States population. SRCCs general trends compared to matching nonvariant adenocarcinomas are earlier age of onset, with initial presentation favoring higher rates of regional or distant disease presentation and poor tumor differentiation. After multivariable analysis, SRCCs typically have worse overall survivals, but substantial variances exist depending on tumor location. Identifying SRCCs at earlier disease stages is likely the single most important intervention to improving outcomes for these patients.