Four Metachronous Cancers: Mutation Profiling Can Be Used to Distinguish Multiple Primary Cancers from Metastases

Distinguishing between primary and metastatic tumors is critical in patients with multiple cancers. We present the case of a man in his 70s with quadruple carcinoma, squamous cell carcinoma in both lungs, invasive urothelial carcinoma of the bladder, and esophageal cancer, discovered during follow-up after sigmoid colon cancer surgery. A histopathological analysis, including immunostaining, could not confirm whether these were primary or metastatic cancer. A comprehensive oncogene mutation analysis using next-generation sequencing revealed distinct gene mutations in each tumor, confirming that all were primary cancers of heterogeneous origin. Our findings highlight the importance of advanced genomic studies on complex cancer cases.