Abstract
Histological transformation is a phenomenon that is well described as one of the causes of tyrosine kinase inhibitor resistance in oncogene-driven non-small-cell lung cancer (NSCLC). The use of immune checkpoint inhibitors (ICIs) as a potential mechanism of acquired resistance to immunotherapy in NSCLC to small-cell lung cancer was also recently found. Here, we report the histological transformation of sarcomatoid carcinoma and metastasis in a lung adenocarcinoma patient without targetable genetic alterations who experienced long-term disease remission after nivolumab therapy. The patient subsequently developed rapid progression in the mediastinal and retroperitoneal lymph nodes, bones, and small intestine. Surgical resection of the small intestine lesion due to acute small intestine bleeding revealed the transformation of NSCLC to sarcomatoid carcinoma. The patient died 3 months after sarcomatoid carcinoma transformation and extensive disease progression, although he was rechallenged with immunotherapy. Genomic and immunohistochemical analyses revealed a comparable abundance of gene mutations and a limited number of immune cells in the tumor microenvironment, with low infiltration of CD8+ T cells, CD4+ T cells, regulatory T cells, and PD-L1+ macrophages in metastatic tumors, revealing a noninflamed immune microenvironment for ICI-resistant tumors.