Perivascular epithelioid cell tumor (PEComa) with TFE3 gene rearrangement: Clinicopathological, immunohistochemical, and molecular features

Abstract

Perivascular epithelioid cell tumors (PEComas) have been increasingly associated with gene rearrangement of the transcription factor E3 (TFE3). We present three cases of PEComa with a TFE3 gene abnormality detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Their clinical features, pathological morphology, and prognosis were investigated. Histologically, the tumors in these three cases showed predominantly epithelioid cells arranged in nests or sheets separated by a delicate vascular network, within two of the three cases nuclear atypia, mitotic figures, and necrosis. All three cases showed strong TFE3 and cathepsin K immunoreactivity and weak to strong reactivity for HMB45. One case of PEComa with TFE3 gene fusion exhibited a benign course. The other two cases of PEComa with both TFE3 translocation and X-chromosome polysomy were histologically malignant and showed aggressive growth. In summary, unusual cases of PEComa with TFE3 gene rearrangement might present malignant histological features and aggressive clinical behavior. Our results add cases to the literature and describe an association of polysomy with aggressive behavior.

PEComa with Transcription Factor E3 Overexpression: A Diagnostic and Therapeutic Challenge

“…This increasingly recognized group of TFE3-rearranged tumors includes TFE3 rearrangement-associated PEComas, melanotic Xp11 translocation renal cancers, or melanotic Xp11 neoplasms [2]. Subsequently, several case reports have highlighted the distinct entity of TFE3-associated PEComas with distinct malignant histological features and relatively aggressive clinical behaviors [3, 4, 5]. TFE3 is a member of the MiT family of transcription factors, which includes MiTF, TFEB, TFEC, and TFE3, which are important for mesenchymal cell differentiation [6].…”

Perivascular epithelioid tumours (PEComas) of the gynaecological tract

“…Translocations involving the TFE3 locus at Xp11.2 have been reported in epithelioid clear cell tumours such as alveolar soft part sarcoma and Xp11.2 translocation-associated renal cell carcinoma. In recent years, 18 cases of TFE3 translocation-associated PEComa have been reported in kidney, 25 89 bladder, 90 colon, 91 92 pelvic soft tissue, 25 ovary, 32 vagina 71 and uterus. 58 71 91 These tumours appear to be characterised by predominantly epithelioid, clear cell morphology without pleomorphism and IHC positivity for HMB-45, TFE3 and Cathepsin K, and negativity for MiTF, 91 92 SMA and desmin.…”

“…58 71 91 These tumours appear to be characterised by predominantly epithelioid, clear cell morphology without pleomorphism and IHC positivity for HMB-45, TFE3 and Cathepsin K, and negativity for MiTF, 91 92 SMA and desmin. 25 within the PEComa family. 71 Activation of the mTOR pathway may not necessarily play a role in these tumours, which has implications with respect to patient entry into clinical trials of mTOR pathway inhibitors.…”

“…Recently, cathepsin K, a transcriptional target of the MiTF family, emerged as a sensitive marker for PEComa. [25][26][27] However, cathepsin K is not specific for PEComa and is commonly positive in melanoma, alveolar soft part sarcoma and mesenchymal tumours, including leiomyosarcoma (LMS). 28 Renal and extrarenal AMLs/PEComas exhibit true melanocytic differentiation in the form of Editor's choice Scan to access more free content melanosomes at various stages of development on electron microscopy 29 30 and positive Masson-Fontana staining.…”

Role of Next-Generation Sequencing as a Diagnostic Tool for the Evaluation of Bone and Soft-Tissue Tumors

“…In addition, a novel DVL2-TFE3 gene fusion was also described. Based on a recent publication, PEComa with a TFE3 gene abnormality shows strong TFE3 and cathepsin K immunoreactivity and weak-to-strong reactivity for HMB45 [52][53][54] . The diagnosis of PEComa is usually based on HE-stained slides combined with IHC.…”