Diagnosis and treatment of malignant PEComa tumours

Abstract

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 cell 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.

Unusual Pediatric Sigmoid Perivascular Epithelioid Cell Tumor with Regional Lymph Node Metastasis Treated Using Gemcitabine and Docetaxel: A Case Report and Literature Review

“…Immunohistochemical discernment of melanocytic differentiation is the most effective approach to differentiating GI PEComa from other tumors, such as GIST, angiomyolipoma, paraganglioma, malignant melanoma, and alveolar soft part sarcoma [2]. Although the precursor or normal counterpart of PEComa remains unde ned [12], HMB-45 continues to be the most sensitive and frequent melanocytic marker in 92%-100% of reports [1,2,23].…”

“…Immunohistochemical discernment of melanocytic differentiation is the most effective approach to differentiating GI PEComa from other tumors, such as GIST, angiomyolipoma, paraganglioma, malignant melanoma, and alveolar soft part sarcoma [2]. Although the precursor or normal counterpart of PEComa remains unde ned [12], HMB-45 continues to be the most sensitive and frequent melanocytic marker in 92%-100% of reports [1,2,23]. Other potential melanocytic markers are melan-A, smooth muscle actin, and microphthalmia transcription factor, which were indicated in 23%-88%, 59%-93%, and 50%-92% of reports, respectively, as well as desmin and caldesmon [1,2,8,10,14,23].…”

“…Perivascular epithelioid cell tumors (PEComas) are extremely rare neoplasms of mesenchymal origin, featuring distinctive morphology, immunohistochemistry, and ultrastructure [1,2]. Angiomyolipomas, lymphangioleiomyomatosis, and clear-cell sugar tumors are some examples of PEComas [1,2].…”

“…Immunohistochemically, PEComas NOS typically exhibit positive melanocytic and myogenic markers, such as human melanoma black 45 (HMB45), melanoma antigen recognized by T cells (melan-A), and smooth muscle actin, and negative expressions of protein S100, cytokeratin, and desmin [9][10][11]. However, the histogenesis and corresponding normal cellular counterpart of PEComa remain unknown [1,3], and a standardized treatment strategy remains unestablished [2].…”

“…The mammalian target of rapamycin (mTOR) inhibitor treatment remains controversial in patients lacking the tuberous sclerosis complex (TSC) gene mutation [5,9]. To date, radical surgical resection is an effective treatment for primary tumor and local recurrence prevention [2]. Herein, we report the case of an adolescent female patient with an unusual PEComa.…”