An increasing number of TFE3 rearrangement–associated tumors, such as TFE3 rearrangement–associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement–associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity metastases. Our data suggest that these tumors belong to a single clinicopathologic spectrum and expand the known characteristics of TFE3 rearrangement–associated tumors.
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*Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing University School of Medicine
§Department of Pathology of the Affiliated Drum Tower Hospital, Nanjing University Medical School
∥Department of Pathology of the First Affiliated Hospital of Nanjing Medical University
¶Department of Pathology of Nanjing Maternity and Child Health Care Hospital
†School of Basic Medical Sciences, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu
‡Department of Pathology, Anhui Medical University, Hefei, Anhui, China
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Q.R. and Q.S. contributed equally.
Conflicts of Interest and Source of Funding: Supported by the National Natural Science Foundation of China (81472391; 81101933; Q.R.), (81171391; 81372743; X.-j.Z.) and (81201187; Z.-y.W.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Correspondence: Xiao-jun Zhou, MD, PhD, Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China (e-mail: email@example.com).