Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Mayo Clin Proc. 2021 Jun;96(6):1470-1489. doi: 10.1016/j.mayocp.2020.11.004. Epub 2021 Jan 29.
To study the clinical features and identify unique renal neoplasia subtypes and their prognostic implications in individuals with tuberous sclerosis complex (TSC).
The Mayo Clinic nephrectomy registry included 37 patients with TSC diagnosed between 1970 and 2018. Four additional patients were identified from the pathology consultation and autopsy files. All available renal tumors were further characterized using immunohistochemistry and fluorescence in situ hybridization. Clinicopathologic features and follow-up were obtained from the medical record. The American Association for Cancer Research Project GENIE registry was accessed using cBioPortal for molecular profiling of angiomyolipoma (AML).
A total of 276 renal tumors from 41 patients were analyzed. Renal tumors were classified into 9 distinct morphological subtypes, with AML predominating (238 [86%]). Interestingly, all these tumors acted in a benign fashion except one renal cell carcinoma with clear cells and fibromyomatous stroma and one epithelioid AML that metastasized. Molecular profiling studies revealed that epithelioid AMLs were enriched for alterations of TP53, RB1, and ATRX. Eight patients died of direct complications of TSC, including 3 of end-stage renal disease. To date, none have died of a renal epithelial neoplasm.
The identification of unique renal neoplasia subtypes may provide important clues to establish a diagnosis of TSC, and in the somatic setting, this finding has important implications for accurate prognostication. These tumors tend to be indolent, and only 2 of 276 tumors in our study exhibited metastatic behavior. Our results support multidisciplinary management with a focus on preservation of renal function.
研究结节性硬化症（TSC）患者的临床特征，并确定其独特的肾肿瘤亚型及其对预后的影响。
梅奥诊所的肾切除术登记处纳入了 1970 年至 2018 年间诊断为 TSC 的 37 例患者。另外从病理咨询和尸检档案中确定了 4 例患者。所有可用的肾肿瘤均进一步通过免疫组织化学和荧光原位杂交进行了特征分析。从病历中获得了临床病理特征和随访信息。通过 cBioPortal 访问了美国癌症研究协会项目 GENIE 登记处，对血管平滑肌脂肪瘤（AML）进行了分子谱分析。
分析了来自 41 名患者的总共 276 个肾肿瘤。将肾肿瘤分为 9 种不同的形态亚型，其中 AML 占主导地位（238 例[86%]）。有趣的是，除了 1 例具有透明细胞和纤维肌性基质的肾细胞癌和 1 例转移的上皮样 AML 外，所有这些肿瘤均表现为良性行为。分子谱研究表明，上皮样 AML 富含 TP53、RB1 和 ATRX 的改变。8 例患者死于 TSC 的直接并发症，包括 3 例终末期肾病。迄今为止，尚无患者死于肾上皮性肿瘤。
确定独特的肾肿瘤亚型可能为建立 TSC 的诊断提供重要线索，在体细胞环境下，这一发现对准确预测预后具有重要意义。这些肿瘤往往呈惰性，在我们的研究中，276 个肿瘤中仅有 2 个表现出转移性行为。我们的结果支持以保护肾功能为重点的多学科管理。
