Transformation of Thoracic SMARCA4-Deficient Undifferentiated Tumour to Squamous Cell Carcinoma: A Case Report

Thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-dUT) is a rare and highly aggressive malignant tumour with poor response to conventional chemotherapy and a poor prognosis, for which there is currently no standard treatment. This article details a case of SMARCA4-dUT in which next-generation sequencing (NGS) revealed a frameshift mutation in SMARCA4 (N259Tfs44), along with high PD-L1 expression (tumour proportion score, TPS 90%) and a high tumour mutational burden (TMB, 24.58 mutations/Mb). The patient achieved a progression-free survival (PFS) of over 32 months following treatment with pembrolizumab combined with conventional chemotherapy. However, the tumour eventually recurred and transformed into SMARCA4-deficient squamous cell carcinoma (SMARCA4-dSCC). To our knowledge, this is the first reported case of histological transformation in SMARCA4-dUT. Immunotherapy may represent a potential treatment option for SMARCA4-dUT, particularly in patients with high TMB and PD-L1 expression.