Acquired SMARCA4 loss during metastatic progression of hepatocellular carcinoma: a case report

SMARCA4 alterations are recognized in various malignancies and associated with tumor aggressiveness and dedifferentiation. However, the dynamic evolution of SMARCA4 expression during hepatocellular carcinoma (HCC) metastasis has rarely been reported. Here, we report a rare case of HCC with acquired loss of nuclear SMARCA4 staining during metastatic progression. Nuclear SMARCA4 staining was partially preserved in the primary hepatic tumor but completely lost in subsequent pulmonary and lymph node metastases. Compared with the primary lesion, metastatic tumors showed reduced hepatocellular differentiation, increased proliferative activity, and altered immunophenotypic profiles. The case highlights dynamic alterations in SMARCA4 expression during the metastatic progression of HCC. This case could offer valuable insights into the diagnosis of distinguishing primary from metastatic lesions in SMARCA4-deficient tumors.