Comprehensive next-generation sequencing reveals double primary colorectal carcinoma missed by diagnostic imaging: A case report

BACKGROUNDMultiple primary colorectal carcinoma (MPCC) is a rare clinical disease, which is challenging to differentiate from metastatic disease using histopathological methods. Next-generation sequencing (NGS) has been employed to identify multiple primary cancers.CASE SUMMARYThis study a rare case of a 63-year-old male patient diagnosed with MPCC by targeted NGS, which was initially missed by radiological evaluation. The patient was found to have two tumors located on the surface of the colorectum which had distinct genomic alterations. Based on wild-type KRAS detected in the unresected tumor, the patient benefited from the epidermal growth factor receptor (EGFR) inhibitor cetuximab treatment, but developed novel mutations including KIF5B-RET fusion, which provides a possible resistance mechanism to anti-EGFR therapy.CONCLUSIONOur case highlights the necessity of using genetic testing for primary tumor diagnosis and the application of serial plasma circulating tumor DNA profiling for dynamic disease monitoring.