Background:Thoracic SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4)-deficient undifferentiated tumor (SMARCA4-UT) is a rare and highly aggressive thoracic malignancy.It predominantly affects male smokers and typically arises in the mediastinum, where rapid tumor growth and early metastasis contribute to a poor prognosis.Recent evidence suggests that this tumor exhibits biological heterogeneity and variable responses to therapy, underscoring the need for further clinical characterization. Case Report:A 67-year-old man presented with dyspnea and superior vena cava syndrome.Computed tomography revealed a 7-cm mass in the anterior and superior mediastinum with suspected lymph node and bone metastases.Histological examination demonstrated a sheet-like proliferation of large atypical cells with rhabdoid features and necrosis.Immunohistochemical analysis showed loss of SMARCA4 (Brahma-related gene 1 BRG1) expression, positivity for cluster of differentiation 34 (CD34) and sex-determining region Y-box 2 (SOX2), weak epithelial membrane antigen expression, preserved integrase interactor 1 (INI1) expression, and negativity for other epithelial markers, fulfilling the diagnostic criteria for SMARCA4-UT.Despite palliative radiotherapy and combination immunotherapy with nivolumab and ipilimumab, the tumor rapidly progressed.The patient developed grade 4 drug-induced pneumonitis; transient stabilization was achieved, but his condition deteriorated.He died 6 months after disease onset.Autopsy revealed widespread metastases with minimal therapeutic effect, highlighting the aggressive clinical course and treatment resistance. Conclusions:SMARCA4-UT is a highly aggressive tumor requiring comprehensive immunohistochemical evaluation for accurate diagnosis.This case highlights the limited efficacy of immune checkpoint inhibitors in a PD-L1-negative setting and underscores the need for more effective therapeutic strategies.
Ichihashi et al. (Mon,) studied this question.