[Thoracic -deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment].

We explored clinicopathological features and treatment strategies for thoracic -deficient undifferentiated tumor (-UT). Thoracic -UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of -UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic -UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic -UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether gene mutation is detected, it should be classified as -deficient tumors. -deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing -UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with -deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. -UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of -UT should enlighten significance for various kinds of -deficient tumors.