Agaimy Abbas, Hartmann Arndt
Institut für Pathologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Deutschland.
Pathologe. 2021 Nov;42(6):571-577. doi: 10.1007/s00292-021-00985-y. Epub 2021 Oct 5.
During the last decades, the SWI/SNF chromatin-remodeling complex has received enormous recognition as a major player in the molecular pathogenesis of diverse neoplasms. Accordingly, SWI/SNF defects affecting different subunits of the complex became defining genetic features in the nosology of different neoplastic entities. In the kidney, loss of SMARCB1(INI1) as a major component of the SWI/SNF complex has emerged as the defining genetic marker for renal medullary carcinoma and pediatric malignant rhabdoid tumor. Diagnosis of these two rare entities is based on a set of defined demographic, clinicopathological, immunophenotypic, and genetic (SMARCB1 loss) criteria. Moreover, the sickle cell trait is considered a prerequisite for renal medullary carcinoma. Current knowledge illustrates that SMARCB1 loss is encountered in three major tumor categories in the kidney: (1) histologically defined neoplasms that are primarily driven by de novo SMARCB1 loss (renal medullary carcinoma and malignant rhabdoid tumor); (2) SMRACB1-deficient renal cell carcinoma (RCC) with variable non-specific histology ranging from collecting duct-like, papillary high-grade (papillary type 2), or medullary-like (lacking sickle cell trait), to fully undifferentiated; and (3) biphasic (dedifferentiated) RCC showing a variable SMARCB1-deficient undifferentiated component. The latter variant most frequently originates from pre-existing clear cell RCC but may rarely superimpose on papillary or chromophobe RCC. This review summarizes the major defining features of the emerging SMARCB1-deficient renal neoplasms. All SMARCB1-deficient carcinomas have a poor prognosis in common. Therefore, exact diagnosis of these tumors is a prerequisite for studies investigating new therapies.
在过去几十年里，SWI/SNF染色质重塑复合体作为多种肿瘤分子发病机制中的主要参与者而备受关注。因此，影响该复合体不同亚基的SWI/SNF缺陷成为不同肿瘤实体分类学中的决定性遗传特征。在肾脏中，作为SWI/SNF复合体主要成分的SMARCB1（INI1）缺失已成为肾髓质癌和儿童恶性横纹肌样瘤的决定性遗传标志物。这两种罕见实体的诊断基于一系列明确的人口统计学、临床病理、免疫表型和遗传（SMARCB1缺失）标准。此外，镰状细胞性状被认为是肾髓质癌的一个先决条件。目前的知识表明，SMARCB1缺失见于肾脏的三大类肿瘤：（1）组织学定义的肿瘤，主要由新生的SMARCB1缺失驱动（肾髓质癌和恶性横纹肌样瘤）；（2）SMRACB1缺陷型肾细胞癌（RCC），具有可变的非特异性组织学，从集合管样、乳头状高级别（2型乳头状）或髓质样（缺乏镰状细胞性状）到完全未分化；（3）双相（去分化）RCC，显示可变的SMARCB1缺陷型未分化成分。后一种变体最常见于先前存在的透明细胞RCC，但很少叠加在乳头状或嫌色细胞RCC上。本综述总结了新出现的SMARCB1缺陷型肾肿瘤的主要决定性特征。所有SMARCB1缺陷型癌都有预后不良的共同特点。因此，准确诊断这些肿瘤是研究新疗法的先决条件。
