Lenvatinib-refractory thymic mucinous carcinoma with PIK3CA mutation

Mucinous adenocarcinoma, a very rare type of thymic carcinoma, is aggressive and has a poor prognosis. The optimal treatment for advanced thymic mucinous adenocarcinoma has not yet been established because of its rarity. An oral multi-tyrosine kinase inhibitor, lenvatinib, was approved for treatment of thymic carcinoma in March 2021 in Japan. However, to the best of our knowledge, there are no published reports concerning lenvatinib for thymic mucinous adenocarcinoma. Herein, we report a 39-year-old woman who presented with a 70 mm multilocular cystic tumor in her left anterior mediastinum and a massive pericardial effusion. We diagnosed a Masaoka stage IVb thymic mucinous adenocarcinoma with multiple metastases to the liver and bones, and pericardial dissemination on the basis of the pathologic findings on examination of a video-assisted thoracoscopic tumor biopsy and radiological examinations. She received paclitaxel-carboplatin-based chemotherapy, but developed a left cerebellar metastasis. Second-line chemotherapy with lenvatinib failed to suppress the tumor. She died of cancer progression 5 months after presentation. Here, we report what we believe to be the first case of a thymic mucinous adenocarcinoma treated with lenvatinib. Our patient's thymic mucinous adenocarcinoma was refractory to both cytotoxic chemotherapy and lenvatinib. Using next-generation sequencing, we identified phosphatidylinositol 3-kinase catalytic subunit alpha mutation in the tumor. We suspected an association between this mutation and resistance to lenvatinib. We therefore recommend performing next-generation sequencing when considering introduction of lenvatinib for thymic mucinous adenocarcinoma. A surgical procedure may be necessary for accurate diagnosis and genetic analysis of this histological tumor type.