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Angiomyolipoma/PEComa: the past, the present…and back to the future
Anna Caliò1, Stefano Marletta2,3, Guido Martignoni1,4
1Department of Diagnostics and Public Health, Section of Pathology, University of Verona.
Purpose Of Review:
This review provides a comprehensive update on renal angiomyolipoma, a mesenchymal neoplasm within the PEComa family. It revisits its historical classification, evolving pathological understanding, and recent molecular insights, emphasizing its relevance in current diagnostic and pathogenetic contexts.
Recent Findings:
Angiomyolipoma/PEComa has transitioned from being considered a hamartoma to a neoplasm with clonal origin and malignant potential in a few epithelioid angiomyolipoma/pure epithelioid PEComa. Advances in immunohistochemistry have identified new markers such as GPNMB, STING, and TRIM63, aiding differential diagnosis. Molecular studies highlight frequent TSC1/TSC2 mutations and mTOR pathway dysregulation. Emerging evidence suggests a noncanonical activation of TFEB via the cGAS-STING pathway in angiomyolipoma/PEComa.
Summary:
A thorough understanding of the histological subtypes and molecular drivers of angiomyolipoma/PEComa is essential for accurate diagnosis and risk stratification. However, the comprehension of its pathophysiological mechanisms remains not completely understood. The cGAS-STING-TFEB axis may explain the unique immunophenotype of the cellular element composing these neoplasms. Furthermore, this pathway could also be related to the unexpected presence of autophagy observed in angiomyolipoma/PEComa, with STING representing the missing piece in this intricate puzzle. Nevertheless, this proposed mechanism requires validation through further research.
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