Metastatic Renal Cell Carcinoma with Fibromyomatous Stroma associated with Tuberous Sclerosis or MTOR, TSC1/TSC2-Mutations: A Series of 4 Cases and a Review of the Literature

Abstract

Renal cell carcinoma with fibromyomatous stroma (RCCfms) are characterized by a constellation of morphologic findings that include elongated tubules lined by cells with clear to pale eosinophilic cytoplasm and intersecting bands of smooth muscle stroma. Consistent immunohistochemistry findings in RCCfms include diffuse positivity for carbonic anhydrase 9 and variable expression of keratin 7. Molecular profiling of such tumors show either pathogenic alterations of the ELOC (TCEB1) gene, or alterations of MTOR, TSC1, and TSC2. MTOR, TSC1/TSC2-altered RCCfms (M/TSC-RCCfms) has been reported both in the sporadic setting and in association with tuberous sclerosis complex (TSC). The importance of accurate diagnosis of M/TSC-RCCfms includes prompting germline testing in the appropriate clinical context. In addition, it can lead to patient management strategies that are focused on the preservation of renal function, as TSC patients often have multifocal and bilateral disease. As diagnostic criteria for M/TSC-RCCfms have only been recently established, additional data are needed to understand the natural history of this disease. Herein, we report 6 patients with metastatic M/TSC-RCCfms, including four patients from our institutional archives (four males, aged 36 to 58 years at nephrectomy), and two additional cases reported in the literature. Five patients had TSC, and the sixth had an MTOR-altered RCCfms. The majority of patients (5/6, 83%) presented with regional lymph node involvement and one patient developed metastases to the lung. All patients were alive at last follow up (median follow-up of 85 months). Our report is intended to raise awareness regarding rare instances of metastatic behavior for M/TSC-RCCfms.