Epidemiology of Signet Ring Cell Adenocarcinomas

Abstract

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.

CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance, and Secondary Cancer Risk Postulation

“…CDH1 gastric cancers present as signet-ring cell adenocarcinomas (SRCCs) with abundant intracellular mucin, and readily metastasize before forming significant macroscopic primary lesions, accounting for their typical late stage at detection [ 15 ]. It is not clear either why CDH1 mutations are linked primarily with gastric cancer and an increased risk of lobular breast cancer, although case reports document the co-existence of CDH1 gastric SRCC with colorectal, appendiceal, and pancreatic cancers [ 16 , 17 , 18 ].…”

Primary signet‐ring cell carcinoma of the lung in an HIV‐positive patient

“…Because of its rarity in the lung as a primary tumor, metastatic disease of different organs is considered in the differential diagnosis. The stomach is the most frequent site of origin, 4 but SRCC has also been reported to involve the breast, urinary bladder, thyroid, and ovary. Moreover, malignant lymphomas and melanomas can sometimes exhibit signet‐ring features 5,6 …”

“Bull's eye” cells in a pleural effusion: Metastatic pulmonary adenocarcinoma

“…Kumar et al 6 found “bull's eye” cells, associated with SRCs, in 6.5% of 199 carcinomatous effusions; they were most likely to occur in lobular carcinoma of the breast, followed by bladder, pulmonary, pancreatic, ovarian, gastric and colorectal cancers. Carcinomas with SRC morphology are uncommon, representing about 0.5% of all malignancies 7 . The presence of the SRCs is associated with younger age, higher stage at diagnosis, an aggressive course, and resistance to chemotherapy 7 .…”

“…Carcinomas with SRC morphology are uncommon, representing about 0.5% of all malignancies 7 . The presence of the SRCs is associated with younger age, higher stage at diagnosis, an aggressive course, and resistance to chemotherapy 7 . Signet Ring Cell Carcinoma (SRCC)s represent a variable proportion of adenocarcinomas of various sites, from less than 1% for breast and lung adenocarcinomas, to 5% for appendiceal and 17% for gastric adenocarcinomas 7 .…”

“…The presence of the SRCs is associated with younger age, higher stage at diagnosis, an aggressive course, and resistance to chemotherapy 7 . Signet Ring Cell Carcinoma (SRCC)s represent a variable proportion of adenocarcinomas of various sites, from less than 1% for breast and lung adenocarcinomas, to 5% for appendiceal and 17% for gastric adenocarcinomas 7 . Lung and breast adenocarcinomas represent less than 3% of all SRCC, but are more likely to be found in pleural fluid, while gastrointestinal tract SRCCs are more prone to involve peritoneal fluid.…”