Diagnosis and treatment of malignant PEComa tumours

PEComa (PEC tumours; perivascular epithelioid cell tumours) is a family of rare tumours of mesenchymal origin, consisting of epithelial perivascular cells expressing melanocytic and myioid markers. This group includes benign tumours — such as angiomyolipoma (AML) of the kidney, and poorly differentiated malignant PEComa tumours with potential for an aggressive clinical course, which is the main focus of this review. PEComas are most often diagnosed in middle-aged women as extensive tumours located in the abdominal cavity or pelvis, manifesting as pain and complaints related to pressure on nearby organs. PEComa tumours should be differentiated from gastrointestinal stromal tumours (GIST), leiomyosarcoma, melanoma metastasis, chromophobic renal cell carcinoma, clear cel sarcoma, and other clear cell component tumours. Somatic inactivating mutations within the TSC1/TSC2 genes, resulting in excessive activation of the mTORC1 complex, are characteristic for this group of tumour. Recently, a separate PEComa subgroup has been distinguished, characterised by the presence of the TFE3 gene fusion, which also causes increased activity of the mTOR signalling pathway. Negative prognostic factors that indicate an increased risk of PEComa malignant biology are most often: tumour size > 5 cm, increased cytological and nuclear atypia, infiltration of surrounding tissues and blood vessels, presence of necrosis, and high mitotic activity. Radical resection remains the primary treatment method for PEComas because these tumours are characterised by high resistance to radiation and chemotherapy. In the case of locally advanced or metastatic disease, only single reports of short-term responses to palliative chemotherapy containing doxorubicin, gemcitabine, or ifosfamide are available in the literature. There are an increasing number of reports, in the form of several case reports and a few retrospective analyses, about the potential effectiveness of using mTOR inhibitors in unresectable cases. These drugs result in a reduction in primary tumour size and metastasis, as well as symptom relief, with controllable side effects. Unfortunately, case reports of complete resistance to mTOR inhibitor therapy are also available.