PDF(Pubmed)
Abstract：
BACKGROUND: SMARCA4 is a component gene of the SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex; undifferentiated tumors associated with its functional deletion have been described in several organs. However, no established treatment for these tumors currently exists.
METHODS: In this study, we report a case of a SMARCA4-deficient undifferentiated urothelial carcinoma with high PD-L1 expression that was effectively treated with nivolumab after early relapse following treatment for non-invasive bladder cancer. The histological morphology of the rhabdoid-like undifferentiated tumor of unknown primary led us to suspect a SWI/SNF-deficient tumor, and subsequent immunostaining led to the diagnosis of a SMARCA4-deficient undifferentiated tumor. This effort also led to the identification of the developmental origin of this SMARCA4-deficient undifferentiated tumor as a non-invasive bladder cancer. We also carried out a detailed immune phenotypic assay on peripheral T cells. In brief, a phenotypic change of CD8+T cells from naive to terminally differentiated effector memory cells was observed.
CONCLUSIONS: Regardless of the organ of cancer origin or cancer type, SWI/SNF-deficient tumors should be suspected in undifferentiated and dedifferentiated tumors, and immune checkpoint inhibitors may be considered as a promising treatment option for this type of tumor. The pathogenesis of SMARCA4-deficient anaplastic tumors awaits further elucidation for therapeutic development.
METHODS: In this study, we report a case of a SMARCA4-deficient undifferentiated urothelial carcinoma with high PD-L1 expression that was effectively treated with nivolumab after early relapse following treatment for non-invasive bladder cancer. The histological morphology of the rhabdoid-like undifferentiated tumor of unknown primary led us to suspect a SWI/SNF-deficient tumor, and subsequent immunostaining led to the diagnosis of a SMARCA4-deficient undifferentiated tumor. This effort also led to the identification of the developmental origin of this SMARCA4-deficient undifferentiated tumor as a non-invasive bladder cancer. We also carried out a detailed immune phenotypic assay on peripheral T cells. In brief, a phenotypic change of CD8+T cells from naive to terminally differentiated effector memory cells was observed.
CONCLUSIONS: Regardless of the organ of cancer origin or cancer type, SWI/SNF-deficient tumors should be suspected in undifferentiated and dedifferentiated tumors, and immune checkpoint inhibitors may be considered as a promising treatment option for this type of tumor. The pathogenesis of SMARCA4-deficient anaplastic tumors awaits further elucidation for therapeutic development.
摘要：
背景：SMARCA4是SWI/SNF（SWItch/蔗糖非发酵性）染色质重塑复合物的组成基因；已在几个器官中描述了与其功能缺失相关的未分化肿瘤。然而,目前尚无针对这些肿瘤的既定治疗方法。
方法：在本研究中，我们报道了1例PD-L1高表达的SMARCA4缺陷型未分化尿路上皮癌,在治疗非浸润性膀胱癌后早期复发后用纳武单抗有效治疗.未知原发的横纹肌样未分化肿瘤的组织学形态使我们怀疑SWI/SNF缺陷肿瘤，随后的免疫染色导致SMARCA4缺陷的未分化肿瘤的诊断。这项努力还导致将这种缺乏SMARCA4的未分化肿瘤的发育起源鉴定为非浸润性膀胱癌。我们还对外周T细胞进行了详细的免疫表型测定。简而言之,观察到CD8+T细胞从初始到最终分化的效应记忆细胞的表型变化。
结论：无论癌症起源器官或癌症类型如何，SWI/SNF缺陷型肿瘤应在未分化和去分化肿瘤中被怀疑，免疫检查点抑制剂可能被认为是这种类型肿瘤的有希望的治疗选择。缺乏SMARCA4的间变性肿瘤的发病机制有待进一步阐明以进行治疗。
方法：在本研究中，我们报道了1例PD-L1高表达的SMARCA4缺陷型未分化尿路上皮癌,在治疗非浸润性膀胱癌后早期复发后用纳武单抗有效治疗.未知原发的横纹肌样未分化肿瘤的组织学形态使我们怀疑SWI/SNF缺陷肿瘤，随后的免疫染色导致SMARCA4缺陷的未分化肿瘤的诊断。这项努力还导致将这种缺乏SMARCA4的未分化肿瘤的发育起源鉴定为非浸润性膀胱癌。我们还对外周T细胞进行了详细的免疫表型测定。简而言之,观察到CD8+T细胞从初始到最终分化的效应记忆细胞的表型变化。
结论：无论癌症起源器官或癌症类型如何，SWI/SNF缺陷型肿瘤应在未分化和去分化肿瘤中被怀疑，免疫检查点抑制剂可能被认为是这种类型肿瘤的有希望的治疗选择。缺乏SMARCA4的间变性肿瘤的发病机制有待进一步阐明以进行治疗。
