Postmortem Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy in a Patient with Metastatic NTRK Gene Fusion-Positive Transverse Colon Cancer During Effective Entrectinib Treatment

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal malignancy-related complication characterized by tumor embolization in small pulmonary arteries, leading to acute respiratory failure and pulmonary hypertension. Neurotrophic tropomyosin receptor kinase (NTRK) gene fusion-positive colorectal cancer (CRC) is resistant to conventional chemotherapy but responds to tropomyosin receptor kinase (TRK) inhibitors. We report a case of a 70-year-old male with advanced transverse colon adenocarcinoma and peritoneal metastases who developed PTTM despite a marked response to entrectinib. Postmortem findings confirmed tumor emboli, fibrocellular intimal thickening, and thrombosis within the pulmonary arteries. Given the aggressive nature of PTTM, treatment strategies must extend beyond tumor suppression to include antiangiogenic therapy and targeted inhibition of cytokines and growth factors. This case underscores the importance of integrating TRK inhibition with approaches that mitigate mediator-induced pulmonary hypertension. Further research into predictive biomarkers and optimized therapeutic strategies combining TRK inhibitors with antiangiogenic agents is warranted to improve outcomes in NTRK fusion-positive CRC patients at risk of PTTM.