Pulmonary carcinoid harboring a KRAS G12C mutation identified through comprehensive genomic profiling and responding...

Pulmonary carcinoids are the pulmonary counterparts of gastrointestinal neuroendocrine tumors (NETs) G1-2. They may cause distant metastasis, leading to a poor prognosis, and requiring chemotherapy. Reports on cases harboring driver gene mutations remain limited. A man in his late 60s visited to JA Onomichi General Hospital because he was suspected of lung cancer. Positron emission tomography/computed tomography (PET/CT) showed a 24-mm nodule in the right upper lobe with abnormal ^18F-fluorodeoxyglucose uptake, and bronchoscopic examination revealed adenocarcinoma. Surgery was planned for stage IA3 lung adenocarcinoma; however, intraoperative findings demonstrated pleural dissemination, and the procedure was terminated as an exploratory thoracotomy. Pathological examination of tissue obtained from the pleural dissemination showed features consistent with NET G2, confirming a diagnosis of atypical carcinoid. Ten months after treatment with carboplatin plus etoposide, salvage surgery consisting of right upper lobectomy and resection of pleural dissemination was performed. Histopathological examination revealed a papillary adenocarcinoma adjacent to a NET G2. Three months after surgery, CT revealed a metastatic lesion in the retrohepatic segment. Histological examination of the liver tumor obtained via laparoscopic hepatectomy confirmed a NET G2 without adenocarcinomatous components. Four months after hepatectomy, PET/CT demonstrated multiple lymph node metastases. The patient was treated sequentially with carboplatin plus etoposide, everolimus, and amrubicin, however, the liver metastases progressed. A liver tumor biopsy was performed for comprehensive genomic profiling (CGP). The biopsy specimen revealed metastatic NET G2. FoundationOne CDx testing identified KRAS G12C mutation, and treatment with sotorasib was initiated. One year has passed since the initiation of sotorasib with no serious adverse events. The liver metastases have regressed, and tumor marker levels have decreased. Sotorasib is effective for treating KRAS G12C-positive pulmonary carcinoids. Because pulmonary NETs rarely harbor driver mutations, CGP testing may be considered.