Cancer of Unknown Primary Most Suggestive of Colorectal Origin With Microsatellite Instability-high Status and High Tumor Mutation Burden Including NTRK Fusion.

BACKGROUND/AIM: Cancer of unknown primary (CUP) is associated with a poor prognosis. Recent advances in comprehensive genomic profiling (CGP) have made it possible to detect actionable mutations in CUP cases, which allows the inference of the primary tumor site. This report demonstrates CUP most suggestive of colorectal origin and highlights how CGP can significantly impact treatment decisions and outcomes.

CASE REPORT: A 73-year-old woman presented with altered consciousness secondary to diabetic ketoacidosis. Imaging revealed a huge mass with abscess formation near the hepatic flexure, but colonoscopy and biopsy failed to identify a definitive primary site. The histopathology of echo-guided percutaneous tumor biopsy showed poorly differentiated adenocarcinoma. Immunohistochemistry revealed that it was positive for cytokeratin (CK) 7, negative for CK20, and slightly positive for caudal type homeobox (CDX) 2. Although colorectal cancer was the most suspected diagnosis based on imaging examination, the patient was still diagnosed with CUP and treated with carboplatin and nab-paclitaxel, resulting in a partial response; however, treatment was discontinued due to adverse effects. CGP revealed microsatellite instability (MSI)-high, high tumor mutation burden (TMB) of 100/Mb, and neurotrophic tropomyosin receptor tyrosine kinase (NTRK) fusion. The patient was subsequently treated with larotrectinib, to achieve further tumor shrinkage. Considering MSI-high and TPM3-NTRK1 fusion in addition to radiological examinations, colorectal cancer was the most suspected diagnosis.

CONCLUSION: CUP is generally associated with poor prognosis. Comprehensive genomic profiling (CGP) offers a promising avenue for discovering personalized and potentially effective therapeutic strategies.