TFE3 Translocation–associated Perivascular Epithelioid Cell Neoplasm (PEComa) of the Gynecologic Tract

Abstract

TFE3 translocation associated PEComa is a distinct form of perivascular epithelioid cell neoplasm, the features of which are poorly defined owing to their general infrequency and limited prior reports with confirmed rearrangement or fusion totaling nine cases. Recent investigation has found a lack of TSC gene mutation in these tumors compared to their nonrearranged counterparts which underscores the importance of recognizing the translocated variant due to hypothetical ineffectiveness of targeted mTOR inhibitor therapy. Six cases were identified and TFE3 rearrangement was confirmed by FISH. Patient age ranged 46 to 66 years (median 50) and none had a history of tuberous sclerosis complex. Three cases arose in the uterine corpus, one in the vagina, and one pelvic tumor and one pulmonary tumor were likely a recurrence/metastasis from a probable uterine primary. Five cases had purely clear cell epithelioid morphology that showed a spectrum of atypia while one case had a mixture of clear cell epithelioid and spindle cells. A mostly consistent immunophenotype was observed in the purely clear cell epithelioid cases: each demonstrated diffuse TFE3, HMB45, CathepsinK labeling, either focal or no melanA staining and variably weak reactivity to smooth muscle markers. The mixed clear cell epithelioid and spindle cell case had a similar pattern in its epithelioid component, but strong muscle marker positivity in its spindle cell component. Follow up ranged 1 to 57 months. Three cases demonstrated aggressive behavior and three cases had no evidence of recurrence. Both GYN-specific and traditional sets of criteria for malignancy were evaluated. The GYN model showed improved inclusion and specificity in comparison to the traditional model.

Perivascular epithelioid tumours (PEComas) of the gynaecological tract

“…The remaining tumours 44 45 48 71 (including three transcription factor E3 (TFE3)-translocation-associated PEComas 71 ) were HMB-45-positive but negative for multiple muscle markers. 71 On ultrastructural examination, seven of ‡Strong or diffuse in three of three cases. §Focally weakly positive in two of three cases and was strongly positive in one of three cases.…”

“…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. 40 PEComas associated with TFE3 translocations are immunoreactive for TFE3, but the converse is not necessarily true; for example, three gynaecological tract PEComas which were TFE3-positive on IHC were negative for TFE3 translocation on fluorescent in-situ hybridisation (FISH).…”

“…40 PEComas associated with TFE3 translocations are immunoreactive for TFE3, but the converse is not necessarily true; for example, three gynaecological tract PEComas which were TFE3-positive on IHC were negative for TFE3 translocation on fluorescent in-situ hybridisation (FISH). 71 Since TFE3 is ubiquitously expressed at a low level in many cell types, the use of sensitive IHC techniques may yield positive IHC results in tumours which lack TFE3 translocations. 91 Therefore, weak IHC staining for TFE3 on should be interpreted with caution.…”

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

“…In a clinical followup study, Agaram et al [55] demonstrated that PEComa patients with TFE3 rearrangement may have a better prognosis. In patients with TSC1/2 mutation, mTOR inhibitors have proven to be effective [56,57] . Especially in patients suffering from malignant/metastatic PEComa, NGS may provide further insight regarding potential treatment strategies.…”

Malignant Pervascular Epitheloid Cell Tumor (PEComa), Presenting as a Large Intra-Abdominal Mass in a Young Woman: A Case Report and Review of Literature

“…She showed extremely poor tolerance to chemotherapy and the tumour size was seen to increase soon after the first cycle with worsening of symptoms. mToR inhibitors have shown good clinical activity and solid molecular basis to have efficacy in this rare tumor [3,4].…”