A rare case of double primary lung adenocarcinomas with uncommon complex EGFR G719X and S768I mutations and pleomorphic carcinoma.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy has emerged as a viable treatment for patients with advanced non-small cell lung cancer with common EGFR mutations. The uncommon G719X and S768I mutations can co-occur as complex mutations in the same tumor. Here we report a case of a 72-year-old male patient with double lung carcinoma, with G719X and S768I complex mutations detected in the right upper lung lobe along with brain metastases. Osimertinib (80 mg/day) was administered as the first-line treatment, and a reduction in the right lobe tumor and brain lesions was achieved. However, the left upper lung lobe mass remained unchanged; histopathological examination via a lobectomy revealed pleomorphic carcinoma. Thus, the patient was diagnosed with multiple primary lung cancers. In conclusion, osimertinib is a viable treatment option for lung cancer with rare EGFR G719X and S768I complex mutations.

Fatal limbic encephalitis as paraneoplastic neurological syndrome in a patient with lung adenocarcinoma positive for antiamphiphysin antibody after durvalumab treatment.

A 69-year-old Japanese male with advanced lung adenocarcinoma developed neurological symptoms after chemoradiotherapy and durvalumab maintenance therapy. He was positive for serum antiamphiphysin antibody, which is rarely seen in patients with lung adenocarcinoma. Additionally, his brain magnetic resonance images showed limbic encephalitis which led to the diagnosis of classic paraneoplastic neurological syndrome (PNS). Immune checkpoint inhibitors (ICIs) activate T cells and may also activate antineuronal antibodies that cause PNS. Durvalumab, which is an ICI, may have led to antiamphiphysin antibody-positive PNS in our patient. Treatment with systemic high-dose methylprednisolone was unsuccessful and he died 2 months later. PNS should be considered as one of the differential diagnoses in patients with lung cancer and neurological symptoms during, or after, ICI treatment.