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YAP1-TFE3 epithelioid hemangioendothelioma: a case without vasoformation and a new transcript variant

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Abstract

Epithelioid hemangioendothelioma is a rare vascular tumor of borderline malignancy characterized by recurrent WWTR1-CAMTA1 gene fusions in approximately 90 % of cases. In addition, a recurrent YAP1-TFE3 gene fusion has been identified in WWTR1-CAMTA1 negative epithelioid hemangioendotheliomas. This subset has been reported as having a distinct morphology with more obvious vasoformation, voluminous eosinophilic cytoplasm, and TFE3 positivity on immunohistochemistry. We report a case of a YAP1-TFE3 translocated epithelioid hemangioendothelioma arising in a groin lymph node in a 29-year-old male. Plump spindle cell morphology and absence of vasoformation made correct diagnosis particularly difficult. Immunohistochemistry showed nuclear positivity for both ERG and TFE3, fluorescence in situ hybridization showed break apart for TFE3 and RT-PCR identified a YAP1 exon1 to TFE3 exon 6 transcript, a previously unreported fusion variant. Awareness of this solid morphology and variant fusion will aid in identification of future cases of this rare vascular tumor.

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References

  1. Antonescu CR (2014) Malignant vascular tumors—an update. Mod Pathol 27(Suppl 1):S30–S38

    Article  CAS  PubMed  Google Scholar 

  2. Antonescu CR, Le Loarer F, Mosquera J-M, Sboner A, Zhang L, Chen C-L, Chen H-W, Pathan N, Krausz T, Dickson BC, Weinreb I, Rubin MA, Hameed M, Fletcher CDM (2013) Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Gene Chromosome Cancer 52:775–784

    Article  CAS  Google Scholar 

  3. Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, Healey JH, Antonescu CR (2011) A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosom Cancer 50:644–653

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Tanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, Hanwright PJ, Flanagan J, Luo Y, Fenwick K, Natrajan R, Mitsopoulos C, Zvelebil M, Hoch BL, Weiss SW, Debiec-Rychter M, Sciot R, West RB, Lazar AJ, Ashworth A, Reis-Filho JS, Lord CJ, Gerstein MB, Rubin MA, Rubin BP (2011) Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med 3:98ra82

    Article  PubMed  Google Scholar 

  5. Flucke U, Vogels RJ, de Saint Aubain Somerhausen N, Creytens DH, Riedl RG, van Gorp JM, Milne AN, Huysentruyt CJ, Verdijk MA, van Asseldonk MM, Suurmeijer AJ, Bras J, Palmedo G, Groenen PJ, Mentzel T (2014) Epithelioid Hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases. Diagn Pathol 9:131

    Article  PubMed Central  PubMed  Google Scholar 

  6. Williams A, Bartle G, Sumathi VP, Meis JM, Mangham DC, Grimer RJ, Kindblom L-G (2011) Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: useful diagnostic tools in cases with unusual histological features. Virchows Arch 458:291–300

    Article  CAS  PubMed  Google Scholar 

  7. Varelas X (2014) The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 141:1614–1626

    Article  CAS  PubMed  Google Scholar 

  8. Vassilev A (2001) TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm. Genes Dev 15:1229–1241

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Beckmann H, Kadesch T (1991) The leucine zipper of TFE3 dictates helix-loop-helix dimerization specificity. Genes Dev 5:1057–1066

    Article  CAS  PubMed  Google Scholar 

  10. Beckmann H, Su LK, Kadesch T (1990) TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer μE3 motif. Genes Dev 4:167–179

    Article  CAS  PubMed  Google Scholar 

  11. Ladanyi M, Lui MY, Antonescu CR, Krause-Boehm A, Meindl A, Argani P, Healey JH, Ueda T, Yoshikawa H, Meloni-Ehrig A, Sorensen PH, Mertens F, Mandahl N, van den Berghe H, Sciot R, Dal Cin P, Bridge J (2001) The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20:48–57

    Article  CAS  PubMed  Google Scholar 

  12. Weterman MA, Wilbrink M, Geurts van Kessel A (1996) Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas. Proc Natl Acad Sci U S A 93:15294–15298

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Sidhar SK, Clark J, Gill S, Hamoudi R, Crew AJ, Gwilliam R, Ross M, Linehan WM, Birdsall S, Shipley J, Cooper CS (1996) The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. Hum Mol Genet 5:1333–1338

    Article  CAS  PubMed  Google Scholar 

  14. Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, Newbury R, Reuter VE, Garvin AJ, Perez-Atayde AR, Fletcher JA, Beckwith JB, Bridge JA, Ladanyi M (2001) Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 159:179–192

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, Debiec-Rychter M, Hutchinson B, Reuter VE, Boccon-Gibod L, Timmons C, Hafez N, Ladanyi M (2002) PRCC-TFE3 renal carcinomas: Morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol 26:1553–1566

    Article  PubMed  Google Scholar 

  16. Clark J, Lu YJ, Sidhar SK, Parker C, Gill S, Smedley D, Hamoudi R, Linehan WM, Shipley J, Cooper CS (1997) Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma. Oncogene 15:2233–2239

    Article  CAS  PubMed  Google Scholar 

  17. Argani P, Lui MY, Couturier J, Bouvier R, Fournet JC, Ladanyi M (2003) A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). Oncogene 22:5374–5378

    Article  CAS  PubMed  Google Scholar 

  18. Tanaka M, Kato K, Gomi K, Matsumoto M, Kudo H, Shinkai M, Ohama Y, Kigasawa H, Tanaka Y (2009) Perivascular epithelioid cell tumor with SFPQ/PSF-TFE3 gene fusion in a patient with advanced neuroblastoma. Am J Surg Pathol 33:1416–1420

    Article  PubMed  Google Scholar 

  19. Weterman MJ, van Groningen JJ, Jansen A, van Kessel AG (2000) Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins. Oncogene 19:69–74

    Article  CAS  PubMed  Google Scholar 

  20. Kobos R, Nagai M, Tsuda M, Merl MY, Saito T, Laé M, Mo Q, Olshen A, Lianoglou S, Leslie C, Ostrovnaya I, Antczak C, Djaballah H, Ladanyi M (2013) Combining integrated genomics and functional genomics to dissect the biology of a cancer-associated, aberrant transcription factor, the ASPSCR1-TFE3 fusion oncoprotein. J Pathol 229:743–754

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Tsuda M, Davis IJ, Argani P, Shukla N, McGill GG, Nagai M, Saito T, Lae M, Fisher DE, Ladanyi M (2007) TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition. Cancer Res 67:919–929

    Article  CAS  PubMed  Google Scholar 

  22. Artandi SE, Merrell K, Avitahl N, Wong K-K, Calame K (1995) TFE3 contains two activation domains, one acidic and the other proline-rich, that synergistically activate transcription. Nucleic Acids Res 23:3865–3871

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Carter JM, Sukov WR, Montgomery E, Goldblum JR, Billings SD, Fritchie KJ, Folpe AL (2014) TGFBR3 and MGEA5 rearrangements in pleomorphic hyalinizing angiectatic tumors and the spectrum of related neoplasms. Am J Surg Pathol 38:1182–1992

    Article  PubMed  Google Scholar 

  24. Nayler SJ, Rubin BP, Calonje E, Chan JK, Fletcher CD (2000) Composite hemangioendothelioma: a complex, low-grade vascular lesion mimicking angiosarcoma. Am J Surg Pathol 24:352–361

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital NHS Foundation Trust, Birmingham, UK

    Florian Puls, Angela Niblett, Jade Clarke & Lars-Gunnar Kindblom

  2. Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, UK

    Tom McCulloch

  3. Department of Musculoskeletal Pathology, (Royal Orthopaedic Hospital NHS Foundation Trust), Robert Aitken Institute of Clinical Research, University of Birmingham, Birmingham, B15 2TT, UK

    Florian Puls

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  1. Florian Puls
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  2. Angela Niblett
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  3. Jade Clarke
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  4. Lars-Gunnar Kindblom
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  5. Tom McCulloch
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Correspondence to Florian Puls.

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Puls, F., Niblett, A., Clarke, J. et al. YAP1-TFE3 epithelioid hemangioendothelioma: a case without vasoformation and a new transcript variant. Virchows Arch 466, 473–478 (2015). https://doi.org/10.1007/s00428-015-1730-y

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  • DOI: https://doi.org/10.1007/s00428-015-1730-y

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