VEGFR Inhibitors for Uterine Metastatic Perivascular Epithelioid Tumors (PEComa) Resistant to mTOR Inhibitors. A Case Report and Review of Literature

Abstract

Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors.

Primitive Cutaneous (P)erivascular (E)pithelioid (C)ell Tumour (PEComa): A New Case Report of a Rare Cutaneous Tumor

“…To date, to our knowledge, only 65 cases of CPEC have been reported, but they are certainly “legitimate”, to which the present case is added. Although there are little molecular data regarding this entity, our case adds to this knowledge, considering the importance of detecting genomic aberrations in the context of specific therapies such as mTOR inhibitors [ 34 ]. Further and future studies with larger case series will be needed to obtain new information and increase our knowledge of this rare entity.…”

Case report: Kidney perivascular epithelioid cell tumor treated with anti-VEGFR tyrosine kinase inhibitor and MTOR inhibitor

“…More recently, Liapi et al. reported a case of uterine metastatic PEComa that progressed on MTOR inhibitor, while subsequent treatment with the VEGFR inhibitor pazopanib led to regression and stability of multiple metastases ( 33 ). Taken together, our report along with other studies suggest that the anti-angiogenic TKIs could be effective for the treatment of some malignant PEComas.…”

Uterine perivascular epithelioid tumors (PEComas) with lung metastasis showed good responses to mTOR and VEGFR inhibitors: A case report

“…Antiangiogenic VEGFR inhibitors also exhibited clinical responses in PEComa patients, but mainly in stabilizing disease in patients with malignant PEComas (ORR = 8.3%, median PFS = 5.4 months) ( 11 , 20 ). The combination of the VEGFR inhibitor, sorafenib, with the mTOR inhibitor, sirolimus, led to a complete response in a uterine PEComa case reported in 2016; however, the patient’s molecular features were not discussed in the study ( 14 ).…”