Clinical presentations and molecular studies of invasive renal epithelioid angiomyolipoma

Abstract

Purpose Epithelioid angiomyolipoma (EAML) is a rare variant of renal angiomyolipoma with malignant potential, and the cytogenetic and clinical behavior of EAML remains a challenging issue. Methods We retrospectively analyze the clinical courses of five EAML, the use of everolimus on metastatic EAML, and next-generation sequencing (NGS) and polymerase chain reaction (PCR) studies to investigate the gene mutation of TSC and the impact of PI3K/Akt/mTOR signaling pathway in metastatic EAML. Results The mean age was 37.8 years, mean tumor size was 13 cm, all patients received radical nephrectomy, one stage IV patient received neoadjuvant mTOR inhibitor management, and one patient with high mitotic activity developed metastasis 1 year after nephrectomy. NGS assay showed a frameshift gene mutation of TSC2 in chromosome 16. PCR array for the mRNA alterations in PI3K/Akt/mTOR signaling pathway of EAML showed high expression of PIP3, AKT, TSC1, mTOR, PDK1, P70, 4E-BP1 and elF4E. Conclusion EAML of the kidney is a specific type of renal AML with malignant potentials, where around 22% of the patients present with invasion or metastasis. Higher mitotic activities indicate a greater metastatic potential, with radical nephrectomy as the treatment of choice, and mTOR inhibitors such as everolimus either as neoadjuvant or adjuvant targeted therapy can lead to a better clinical outcome. NGS to explore the mTOR signaling pathway may help us to better understand the pathogenesis and progression of EAML.