ArticleThe American journal of case reports2026
Thoracic SMARCA4-Deficient Undifferentiated Tumor Presenting as a Giant Mediastinal Mass: A Case Report.
Article in The American journal of case reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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