[50] A Subset of PEComas Harbor TFE3 Gene Fusions

P Argani, P Illei, G Netto, J Ro, HY Cho, S Dogan, M Ladanyi, G Martignoni, S Aulmann, SW Weiss. Johns Hopkins Medical Institutions, Baltimore, MD; Asan Medical Center, Seoul, Korea; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Verona, Verona, Italy; University of Heidelberg, Heidelberg, Germany; Emory University, Atlanta, GA

Background: Perivascular epithelioid cell neoplasms (PEComas) include the common renal angiomyolipoma, pulmonary clear cell sugar tumor and lymphangioleiomyomatosis, and less common neoplasms of soft tissue, gynecologic and gastrointestinal tracts. Recently, aberrant immunoreactivity for TFE3 protein (a sensitive and specific marker of neoplasms harboring TFE3 gene fusions) has been reported in as many as 80% of PEComas. TFE3 gene status in these neoplasms has not been systematically investigated, though a recent case report has documented a PSF-TFE3 gene fusion in an extrarenal PEComa.
Design: We used a fluorescence in situ hybridization (FISH) break-apart assay to evaluate for TFE3 gene fusions in archival material from 26 PEComas. These cases included 2 previously published TFE3 immunoreactive non-renal PEComas, 12 additional non-renal PEComas (5 soft tissue, 4 abdominal, 2 uterine, 1 hepatic), and 12 renal angiomyolipomas with predominant spindle or epithelioid morphology. Results were correlated with TFE3 immunoreactivity and clinicopathologic features.
Results: Three non-renal PEComas (mean patient age 19 years) demonstrated TFE3 gene fusions by FISH; all three demonstrated strong positive (3+) TFE3 immunoreactivity. Two of these cases had adequate mRNA for RT-PCR analysis, and neither harbored a PSF-TFE3 gene fusion. In addition, a metastasis of a uterine PEComa which showed moderate positive (2+) TFE3 immunoreactivity demonstrated TFE3 gene amplification, a previously unreported phenomenon. None of the other 22 PEComas (mean patient age 54 years) demonstrated TFE3 gene alterations, though 4 demonstrated moderate positive (2+) TFE3 immunoreactivity. All 4 PEComas with TFE3 alterations immunolabeled strongly for Cathepsin K, similar to other PEComas.
Conclusions: A subset of PEComas harbor TFE3 gene fusions. While numbers are small, distinctive features of these cases include young age, extrarenal location, absence of association with tuberous sclerosis (TS), predominant epithelioid clear cell morphology, minimal immunoreactivity for muscle markers, and strong (3+) TFE3 immunoreactivity. Despite significant morphologic overlap with other PEComas, PEComas harboring TFE3 gene fusions may represent a distinctive entity.
Category: Bone & Soft Tissue

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 8, Tuesday Morning


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