PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity.
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.
*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.
Qiu
Q
Rao
Qin
Q
Shen
Qiu-yuan
QY
Xia
Zi-yu
ZY
Wang
Biao
B
Liu
Shan-shan
SS
Shi
Qun-li
QL
Shi
Hong-lin
HL
Yin
Bo
B
Wu
Sheng-bing
SB
Ye
Li
L
Li
Jie-Yu
JY
Chen
Min-hong
MH
Pan
Qing
Q
Li
Rui
R
Li
Xuan
X
Wang
Ru-song
RS
Zhang
Bo
B
Yu
Heng-hui
HH
Ma
Zhen-feng
ZF
Lu
Xiao-jun
XJ
Zhou
D000293:Adolescent; D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000032:analysis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002648:Child; D041321:Chromosomes, Human, X; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D008938:Mitosis; D025202:Molecular Diagnostic Techniques; D000072670:PTB-Associated Splicing Factor; D054973:Perivascular Epithelioid Cell Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014178:Translocation, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D000072670:PTB-Associated Splicing Factor; D016601:RNA-Binding Proteins; C069203:TFE3 protein, human