Primary collision lung adenocarcinoma harboring EGFR exon 21 L858R and KRAS G12C mutations: A case report

Pulmonary collision tumors are characterized by the coexistence of two morphologically and genetically distinct neoplasms within a single lesion. We report a rare case of primary collision lung adenocarcinoma harboring two mutually exclusive driver mutations, EGFR exon 21 L858R and KRAS G12C. A 77-year-old man with a history of smoking was diagnosed with lung adenocarcinoma. Preoperative molecular testing of a transbronchial biopsy specimen suggested the coexistence of EGFR L858R and KRAS G12C mutations. Pathological findings of the surgically resected tumor exhibited solid and papillary architecture, with a lepidic pattern at the periphery. DNA was extracted separately from the solid/papillary and lepidic components for molecular analysis. The solid/papillary component harbored a KRAS G12C mutation but lacked an EGFR mutation, with a PD-L1 tumor proportion score (TPS) of 5%. In contrast, the lepidic component harbored an EGFR L858R mutation without a KRAS mutation and had a PD-L1 TPS of <1%. These findings supported the diagnosis of a collision tumor composed of KRAS - and EGFR -mutated adenocarcinomas. Despite adjuvant chemotherapy and immunotherapy, the patient developed recurrence of solitary bone metastasis. Molecular testing of the bone biopsy revealed the presence of a KRAS G12C mutation but no EGFR mutation. This case highlights the biological complexity of collision tumors and the clinical importance of repeated biopsies for guiding treatment. Recognizing genetically distinct tumor populations within a single lesion is crucial for accurate diagnosis and optimal therapeutic decision making.