Abstract
Pulmonary pleomorphic carcinoma (PPC) is a rare, aggressive non-small cell lung cancer (NSCLC) subtype characterized by rapid progression and challenging diagnosis from a limited biopsy. These challenges delay treatment initiation. Comprehensive genomic panel profiling helps identify actionable driver mutations, such as mesenchymal-epithelial transition factor (MET) exon 14 skipping mutations, enabling molecular targeted therapy planning. We present a case of an older female patient with suspected NSCLC and rapid clinical deterioration, where biopsy did not confirm the specific subtype. Genotype testing identified a MET exon 14 skipping mutation. A MET inhibitor treatment was planned; however, the patient died before treatment began. Postmortem autopsy confirmed the diagnosis of PPC. This case highlights the importance of early comprehensive genomic profiling in suspected NSCLC with inconclusive histology based on a fine-needle biopsy (FNB) to facilitate timely and potentially beneficial therapeutic planning in rapidly progressing malignancies such as PPC.