Primary Colorectal Signet Ring Cell Carcinoma and the Risk of Multiple Primary Gastrointestinal Malignancies: A
Belal Mohamed Hamed1, Asmaa Ellaithy2, Alzahraa Faris Alesawy3
1Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Background:
Signet-ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer, constituting 0.5-2.5% of all adenocarcinomas. It is characterized by signet ring cells as the dominant malignant cell type. Developing gastrointestinal (GI) second primary malignancies (SPMs) after SRCC is a rare event reported in the literature and insufficiently addressed. This study aimed to explore this gap and provide updated evidence about this rare cancer.
Methods:
Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio (SIR) analyses with multiple outcome assessment were performed, applying a two-month latency exclusion period to evaluate the risk of GI SPMs in patients diagnosed with primary colorectal SRCC. The SIR was calculated as observed/expected (O/E), with excess absolute risk (EAR) per 10,000. Significance was achieved at 0.05 with a 95% confidence interval (CI).
Results:
There was an increased risk for GI SPMs after SRCC in the 2-11 months interval (O/E=2.49, P<0.05, EAR=37.31), and over 10 years of follow-up (O/E=3.08, P<0.05, EAR=59.20). Small intestine SPMs in the 2-11 months interval had an O/E of 4.17 (P<0.05, 95% CI: 0.11-23.26, EAR=1.97), with an overall O/E of 9.62 (P<0.05, EAR=6.32). No events of GI SPMs were observed among young patients during follow-up (O/E=1.05, P>0.05, EAR=0.12). Young patients had lack of observed events for GI SPMs (O/E=0.00, EAR=-0.15), compared to middle-aged (O/E=7.66, P<0.05) and elderly patients (O/E=2.36, P<0.05). Patients received chemotherapy showed a slightly higher observed incidence of SPMs (O/E=2.39, P<0.05, EAR=49.29); however, this finding should be interpreted cautiously given known limitations of chemotherapy data within the SEER database.
Conclusion:
Patients diagnosed with colorectal SRCC are at a significantly increased risk of developing GI SPMs. Given the poor overall prognosis of colorectal SRCC, early surveillance protocols must be carefully contextualized at short intervals (6-12 months) for early detection of GI SPMs. However, a reduced intensity surveillance is recommended beyond 3-5 years to integrate prevention with long-term follow-up. Recommendations should be tailored according to patients' risk profiles with individualized patient focused programs.
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