Renal angiomyolipomas (AMLs) are typically benign, fat-rich mesenchymal tumours composed of vascular, smooth muscle, and adipose elements. However, rare fat-poor subtypes, particularly epithelioid angiomyolipoma (EAML), pose significant diagnostic and therapeutic challenges due to their malignant potential and morphological overlap with renal cell carcinoma (RCC). EAML represents less than 1% of AMLs but differs markedly in its biological behaviour, with a propensity for local invasion, lymphadenopathy, and distant metastasis, most commonly to the lungs and liver. Preoperative diagnosis is often delayed or incorrect, as imaging may fail to detect fat-deficient lesions, making histopathological evaluation necessary. EAML is defined by sheets of polygonal epithelioid cells with eosinophilic or clear cytoplasm, prominent nucleoli, and frequent mitotic figures. Genetic alterations in TSC1/TSC2 and activation of the mTOR pathway are central to pathogenesis, particularly in tuberous sclerosis complex-associated cases. Management hinges on surgical resection, yet recurrence and metastasis may occur years after nephrectomy. mTOR inhibitors have demonstrated efficacy in tumour reduction, especially in TSC-linked cases, while VEGF pathway inhibitors and immune checkpoint blockade represent promising but underexplored avenues. Prognostic features include tumour size >9 cm, necrosis, vascular invasion, and high epithelioid cell proportion. Given the rarity and aggressive potential of EAML, long-term surveillance and multidisciplinary care are essential. Continued research into molecular drivers and targeted therapies will be critical to improving diagnostic precision and patient outcomes.
Keywords: Angiomyolipoma; immunotherapy; renal cell carcinoma; review; targeted therapy; tyrosine kinase inhibitors.
©2025 The Author(s). Published by the International Institute of Anticancer Research.