SMARCA4/BRG1 protein–deficient thoracic tumors (SD-TT) constitute a significant percentage of thoracic malignancies with reasonable fear of being inappropriately classified as non-small cell carcinoma–not otherwise specified (NSCC-NOS) and subjected to molecular testing. Overlapping histomorphology of SMARCA4/BRG1 protein–deficient lung adenocarcinoma (SD-LUAD), SD-TS, and other lung adenocarcinomas necessitates more exhaustive immunophenotyping than allowed with the current diagnostic pathway for small lung biopsy. There is uncertainty as to whether the histogenesis of SD-TS represents undifferentiated/dedifferentiated carcinomas or de novo genesis. Furthermore, SMARCA4/BRG1 protein–deficient thoracic sarcoma (SD-TS) is also recognized more frequently, primarily due to rising awareness of its existence. SMARCA4-inactivating mutations and consequent loss of functional SMARCA4/BRG1 protein are observed in many tumor types and are observed in 8.43% of non–small cell lung cancers (NSCLC).
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