Perivascular Epithelioid Cell Tumor With SFPQ/PSF-TFE3 Gene Fusion in a Patient With Advanced Neuroblastoma

Abstract

We report a case of perivascular epithelioid cell tumor (PEComa) with an SFPQ/PSF-TFE3 gene fusion in a 14-year-old girl treated for adrenal neuroblastoma for 4 years. Imaging studies revealed a tumor in the wall of the sigmoid colon, which was radiologically different from the neuroblastoma, together with several inguinal and cervical lymph node metastases of the neuroblastoma. Microscopically, the tumor in the sigmoid colon showed sheet-like growth of epithelioid cells with abundant clear cytoplasm and round nuclei, which were separated by thin fibrovascular septa. These epithelioid cells were immunohistochemically positive for vimentin, gp100 (detected with monoclonal antibody HMB-45), and TFE3, and the tumor was diagnosed as PEComa. In a fluorescence in situ hybridization assay using an in-house probe for TFE3, the tumor cells showed split signals, indicating a rearrangement of TFE3. Molecular cloning using 5' rapid amplification of complementary DNA ends and subsequent reverse transcription-polymerase chain reaction revealed an SFPQ/PSF-TFE3 gene fusion. To the best of our knowledge, this is the second reported case of metachronous PEComa subsequent to a primary tumor, and the first report confirming an SFPQ/PSF-TFE3 gene fusion in PEComa.

Technique for differentiating alveolar soft part sarcoma from other tumors in paraffin-embedded tissue: comparison of immunohistochemistry for TFE3 and CD147 and of reverse transcription polymerase chain reaction for ASPSCR1-TFE3 fusion transcript

“…In fact, 9 different types of tumors with TFE3 immunoreactivity are known [8,9]. Strong TFE3 immunoreactivity has been reported in a subset of perivascular epithelioid cell tumor and RCCs due to genetic alterations involving TFE3 [8,10,11,17]. These results indicate that TFE3-positive findings do not always lead to a confirmed diagnosis.…”

“…TFE3 immunoreactivity is highly sensitive and specific for ASPS; however, this specificity was not mutually exclusive. More recently, in a subset of perivascular epithelioid cell tumor, gene fusion involving the TFE3 gene has been reported [10,11]. Strong immunoreactivities for monocarboxylate transporter 1 and its interacting partner CD147 have been reported for the cytoplasm of ASPS tumor cells.…”

Ocular perivascular epithelioid cell tumor: report of 2 cases with distinct clinical presentations

“…(5) ASPS are typically negative for "melanocytic" markers (extremely rare exceptions noted). (6) ASPS exhibits t(X;17), whereas PEComa has been found to have a t(X;1) translocation [7][8][9].…”

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

“…27 In addition to alveolar soft part sarcoma and Xp11.2 renal cell carcinoma, rearrangements of TFE3 have also recently been identified in PEComas; TFE3 expression was shown using IHC in five of 17 cases and fusion of PSF/TFE3 was established in one case by RT-PCR and FISH. 54,55 Subsequently, four extra-renal site TFE3-rearranged PEComas were identified that suggested an association with younger age, lack of tuberous sclerosis, and prominent epithelioid cells with alveolar architecture, although fusion with PSF was not detected in the two cases tested. 33 In summary, we have validated a FISH probe set for use in formalin-fixed, paraffin-embedded tissues to detect TFE3 rearrangement with a reflex strategy to identify TFE3/ASPSCR1 fusion.…”