PEComas revisited: mTOR-driven and TFE3-rearranged tumors as distinct biological entities
DOI:
https://doi.org/10.14748/c6bcxy09Keywords:
perivascular epithelioid cell neoplasms (PEComas), TFE3 rearrangement, TSC1/2 PEComas, molecular characteristics, treatment strategiesAbstract
Perivascular epithelioid cell tumors (PEComas) are a rare and fascinating group of mesenchymal neoplasms that can arise in the female reproductive system as well as in extra-gynecologic sites. The first reported case, described in 1996, involved a 57-year-old woman who presented with abnormal vaginal bleeding and a polypoid mass extending into the uterine cavity. Histologically, these tumors are distinctive, consisting of perivascular epithelioid cells that show both smooth muscle and melanocytic differentiation.
Molecular studies have revealed two major biological subtypes of PEComas: (i) tumors harboring TSC1/TSC2 mutations leading to constitutive activation of the mTOR pathway, and (ii) tumors defined by TFE3 gene rearrangements which display distinct clinicopathological and molecular features. PEComas with TFE3 rearrangement represent a separate biological entity, with prognosis influenced by tumor size, location, and histological features. The aim of this review is to summarize current knowledge on the molecular classification, diagnostic approach, and therapeutic management of PEComas, with particular emphasis on the biological and clinical differences between TSC1/TSC2-mutated and TFE3-rearranged tumors.
Given their unpredictable malignant potential, surgical resection remains the cornerstone of treatment, while systemic therapy decisions increasingly rely on molecular profiling. Understanding the molecular landscape of these tumors is essential for optimizing patient management and guiding targeted therapeutic strategies.
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