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Soft Tissue Tumors

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Practical Oncologic Molecular Pathology

Part of the book series: Practical Anatomic Pathology ((PAP))

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Abstract

The world of soft tissue pathology is ever changing, and many of the lesions encountered have characteristic gene fusions or mutations that can be assessed for both diagnostic and in some cases prognostic purposes. This chapter will discuss the role of molecular testing in round cell sarcomas as well as the more commonly tested adipocytic, vascular, skeletal muscle, fibroblastic/myofibroblastic neoplasms, and tumors of uncertain differentiation. A discussion of the role of various testing methods (e.g. FISH, NGS) will be discussed as well as any potential pitfalls or limitations. This discussion will be done in a question and answer format followed by a case-based presentation to reinforce some of the concepts.

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References

  1. Board WCoTE. Soft tissue and bone tumours: international agency for research on cancer; 2020.

    Google Scholar 

  2. Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992;359(6391):162–5.

    Article  CAS  PubMed  Google Scholar 

  3. Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, et al. The Ewing family of tumors – a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 1994;331(5):294–9.

    Article  CAS  PubMed  Google Scholar 

  4. Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, et al. A variant Ewing’s sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995;10(6):1229–34.

    CAS  PubMed  Google Scholar 

  5. Kaneko Y, Yoshida K, Handa M, Toyoda Y, Nishihira H, Tanaka Y, et al. Fusion of an ETS-family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer. 1996;15(2):115–21.

    Article  CAS  PubMed  Google Scholar 

  6. Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H, et al. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene. 1997;14(10):1159–64.

    Article  CAS  PubMed  Google Scholar 

  7. Shing DC, McMullan DJ, Roberts P, Smith K, Chin SF, Nicholson J, et al. FUS/ERG gene fusions in Ewing’s tumors. Cancer Res. 2003;63(15):4568–76.

    CAS  PubMed  Google Scholar 

  8. Ng TL, O’Sullivan MJ, Pallen CJ, Hayes M, Clarkson PW, Winstanley M, et al. Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn. 2007;9(4):459–63.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bridge JA, Sumegi J, Druta M, Bui MM, Henderson-Jackson E, Linos K, et al. Clinical, pathological, and genomic features of EWSR1-PATZ1 fusion sarcoma. Mod Pathol. 2019;32(11):1593–604.

    Article  PubMed  Google Scholar 

  10. Koelsche C, Kriegsmann M, Kommoss FKF, Stichel D, Kriegsmann K, Vokuhl C, et al. DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma. J Cancer Res Clin Oncol. 2019;145(5):1273–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Watson S, Perrin V, Guillemot D, Reynaud S, Coindre JM, Karanian M, et al. Transcriptomic definition of molecular subgroups of small round cell sarcomas. J Pathol. 2018;245(1):29–40.

    Article  CAS  PubMed  Google Scholar 

  12. Solomon DA, Brohl AS, Khan J, Miettinen M. Clinicopathologic features of a second patient with Ewing-like sarcoma harboring CIC-FOXO4 gene fusion. Am J Surg Pathol. 2014;38(12):1724–5.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sugita S, Arai Y, Tonooka A, Hama N, Totoki Y, Fujii T, et al. A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma. Am J Surg Pathol. 2014;38(11):1571–6.

    Article  PubMed  Google Scholar 

  14. Le Loarer F, Pissaloux D, Watson S, Godfraind C, Galmiche-Rolland L, Silva K, et al. Clinicopathologic features of CIC-NUTM1 sarcomas, a new molecular variant of the family of CIC-fused sarcomas. Am J Surg Pathol. 2019;43(2):268–76.

    Article  PubMed  Google Scholar 

  15. Sugita S, Arai Y, Aoyama T, Asanuma H, Mukai W, Hama N, et al. NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma. Hum Pathol. 2017;65:225–30.

    Article  CAS  PubMed  Google Scholar 

  16. Smith SC, Buehler D, Choi EY, McHugh JB, Rubin BP, Billings SD, et al. CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression. Mod Pathol. 2015;28(1):57–68.

    Article  CAS  PubMed  Google Scholar 

  17. Huang SC, Zhang L, Sung YS, Chen CL, Kao YC, Agaram NP, et al. Recurrent CIC gene abnormalities in Angiosarcomas: a molecular study of 120 cases with concurrent investigation of PLCG1, KDR, MYC, and FLT4 gene alterations. Am J Surg Pathol. 2016;40(5):645–55.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Antonescu CR, Owosho AA, Zhang L, Chen S, Deniz K, Huryn JM, et al. Sarcomas with CIC-rearrangements are a distinct pathologic entity with aggressive outcome: a clinicopathologic and molecular study of 115 cases. Am J Surg Pathol. 2017;41(7):941–9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kao YC, Owosho AA, Sung YS, Zhang L, Fujisawa Y, Lee JC, et al. BCOR-CCNB3 fusion positive sarcomas: a clinicopathologic and molecular analysis of 36 cases with comparison to morphologic spectrum and clinical behavior of other round cell sarcomas. Am J Surg Pathol. 2018;42(5):604–15.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Specht K, Zhang L, Sung YS, Nucci M, Dry S, Vaiyapuri S, et al. Novel BCOR-MAML3 and ZC3H7B-BCOR gene fusions in undifferentiated small blue round cell sarcomas. Am J Surg Pathol. 2016;40(4):433–42.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Krskova L, Kabickova E, Drahokoupilova E, Kopeckova K, Plank L, Vitkova P, et al. An undifferentiated sarcoma with BCOR-CCNB3 fusion transcript – pathological and clinical retrospective study. Neoplasma. 2018;65(4):630–6.

    Article  CAS  PubMed  Google Scholar 

  22. Yamada Y, Kuda M, Kohashi K, Yamamoto H, Takemoto J, Ishii T, et al. Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes. Virchows Arch. 2017;470(4):373–80.

    Article  CAS  PubMed  Google Scholar 

  23. Huang SC, Zhang L, Sung YS, Chen CL, Kao YC, Agaram NP, et al. Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: potential pitfalls in interpreting EWSR1 FISH results. Genes Chromosomes Cancer. 2016;55(10):767–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mantilla JG, Ricciotti RW, Chen E, Hoch BL, Liu YJ. Detecting disease-defining gene fusions in unclassified round cell sarcomas using anchored multiplex PCR/targeted RNA next-generation sequencing-molecular and clinicopathological characterization of 16 cases. Genes Chromosomes Cancer. 2019;58(10):713–22.

    Article  CAS  PubMed  Google Scholar 

  25. Rekhi B, Kembhavi P, Mishra SN, Shetty O, Bajpai J, Puri A. Clinicopathologic features of undifferentiated round cell sarcomas of bone & soft tissues: an attempt to unravel the BCOR-CCNB3- & CIC-DUX4-positive sarcomas. Indian J Med Res. 2019;150(6):557–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Italiano A, Chen CL, Thomas R, Breen M, Bonnet F, Sevenet N, et al. Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: a pattern distinct from other sarcomas with complex genomics. Cancer. 2012;118(23):5878–87.

    Article  CAS  PubMed  Google Scholar 

  27. Yoshida A, Arai Y, Kobayashi E, Yonemori K, Ogura K, Hama N, et al. CIC break-apart fluorescence in-situ hybridization misses a subset of CIC-DUX4 sarcomas: a clinicopathological and molecular study. Histopathology. 2017;71(3):461–9.

    Article  PubMed  Google Scholar 

  28. Hung YP, Fletcher CD, Hornick JL. Evaluation of ETV4 and WT1 expression in CIC-rearranged sarcomas and histologic mimics. Mod Pathol. 2016;29(11):1324–34.

    Article  CAS  PubMed  Google Scholar 

  29. Kao YC, Sung YS, Chen CL, Zhang L, Dickson BC, Swanson D, et al. ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements. Genes Chromosomes Cancer. 2017;56(6):501–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Panagopoulos I, Gorunova L, Bjerkehagen B, Heim S. The “grep” command but not FusionMap, FusionFinder or ChimeraScan captures the CIC-DUX4 fusion gene from whole transcriptome sequencing data on a small round cell tumor with t(4;19)(q35;q13). PLoS One. 2014;9(6):e99439.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Kashima T, Halai D, Ye H, Hing SN, Delaney D, Pollock R, et al. Sensitivity of MDM2 amplification and unexpected multiple faint alphoid 12 (alpha 12 satellite sequences) signals in atypical lipomatous tumor. Mod Pathol. 2012;25(10):1384–96.

    Article  CAS  PubMed  Google Scholar 

  32. Sirvent N, Coindre JM, Maire G, Hostein I, Keslair F, Guillou L, et al. Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol. 2007;31(10):1476–89.

    Article  PubMed  Google Scholar 

  33. Clay MR, Martinez AP, Weiss SW, Edgar MA. MDM2 and CDK4 immunohistochemistry: should it be used in problematic differentiated lipomatous tumors?: a new perspective. Am J Surg Pathol. 2016;40(12):1647–52.

    Article  PubMed  Google Scholar 

  34. Dal Cin P, Kools P, Sciot R, De Wever I, Van Damme B, Van de Ven W, et al. Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors. Cancer Genet Cytogenet. 1993;68(2):85–90.

    Article  CAS  PubMed  Google Scholar 

  35. Clay MR, Martinez AP, Weiss SW, Edgar MA. MDM2 amplification in problematic lipomatous tumors: analysis of FISH testing criteria. Am J Surg Pathol. 2015;39(10):1433–9.

    Article  PubMed  Google Scholar 

  36. Zhang H, Erickson-Johnson M, Wang X, Oliveira JL, Nascimento AG, Sim FH, et al. Molecular testing for lipomatous tumors: critical analysis and test recommendations based on the analysis of 405 extremity-based tumors. Am J Surg Pathol. 2010;34(9):1304–11.

    Article  PubMed  Google Scholar 

  37. Robinson DR, Wu YM, Kalyana-Sundaram S, Cao X, Lonigro RJ, Sung YS, et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet. 2013;45(2):180–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Doyle LA, Tao D, Marino-Enriquez A. STAT6 is amplified in a subset of dedifferentiated liposarcoma. Mod Pathol. 2014;27(9):1231–7.

    Article  CAS  PubMed  Google Scholar 

  39. Mantilla JG, Ricciotti RW, Chen EY, Liu YJ, Hoch BL. Amplification of DNA damage-inducible transcript 3 (DDIT3) is associated with myxoid liposarcoma-like morphology and homologous lipoblastic differentiation in dedifferentiated liposarcoma. Mod Pathol. 2019;32(4):585–92.

    Article  CAS  PubMed  Google Scholar 

  40. Crozat A, Aman P, Mandahl N, Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993;363(6430):640–4.

    Article  CAS  PubMed  Google Scholar 

  41. Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N, Aman P. Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia. Oncogene. 1997;15(11):1357–62.

    Article  CAS  PubMed  Google Scholar 

  42. Narendra S, Valente A, Tull J, Zhang S. DDIT3 gene break-apart as a molecular marker for diagnosis of myxoid liposarcoma – assay validation and clinical experience. Diagn Mol Pathol. 2011;20(4):218–24.

    Article  CAS  PubMed  Google Scholar 

  43. Koelsche C, Renner M, Hartmann W, Brandt R, Lehner B, Waldburger N, et al. TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities. J Exp Clin Cancer Res. 2014;33:33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Trautmann M, Cyra M, Isfort I, Jeiler B, Kruger A, Grunewald I, et al. Phosphatidylinositol-3-kinase (PI3K)/Akt signaling is functionally essential in myxoid liposarcoma. Mol Cancer Ther. 2019;18(4):834–44.

    Article  CAS  PubMed  Google Scholar 

  45. Antonescu CR, Tschernyavsky SJ, Decuseara R, Leung DH, Woodruff JM, Brennan MF, et al. Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res. 2001;7(12):3977–87.

    CAS  PubMed  Google Scholar 

  46. Huang SC, Zhang L, Sung YS, Chen CL, Krausz T, Dickson BC, et al. Frequent FOS gene rearrangements in epithelioid hemangioma: a molecular study of 58 cases with morphologic reappraisal. Am J Surg Pathol. 2015;39(10):1313–21.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Adam J, Adamova D, Aggarwal MM, Rinella GA, Agnello M, Agrawal N, et al. Measurement of pion, kaon and proton production in proton-proton collisions at [formula: see text] TeV. Eur Phys J C Part Fields. 2015;75(5):226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. van IDG, de Jong D, Romagosa C, Picci P, Benassi MS, Gambarotti M, et al. Fusion events lead to truncation of FOS in epithelioid hemangioma of bone. Genes Chromosomes Cancer. 2015;54(9):565–74.

    Article  CAS  Google Scholar 

  49. Agaram NP, Zhang L, Cotzia P, Antonescu CR. Expanding the Spectrum of genetic alterations in pseudomyogenic hemangioendothelioma with recurrent novel ACTB-FOSB gene fusions. Am J Surg Pathol. 2018;42(12):1653–61.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Antonescu CR, Chen HW, Zhang L, Sung YS, Panicek D, Agaram NP, et al. ZFP36-FOSB fusion defines a subset of epithelioid hemangioma with atypical features. Genes Chromosomes Cancer. 2014;53(11):951–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol. 2003;27(1):48–57.

    Article  PubMed  Google Scholar 

  52. Hornick JL, Fletcher CD. Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior. Am J Surg Pathol. 2011;35(2):190–201.

    Article  PubMed  Google Scholar 

  53. Walther C, Tayebwa J, Lilljebjorn H, Magnusson L, Nilsson J, von Steyern FV, et al. A novel SERPINE1-FOSB fusion gene results in transcriptional up-regulation of FOSB in pseudomyogenic haemangioendothelioma. J Pathol. 2014;232(5):534–40.

    Article  CAS  PubMed  Google Scholar 

  54. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer. 1982;50(5):970–81.

    Article  CAS  PubMed  Google Scholar 

  55. Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, et al. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer. 2011;50(8):644–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Antonescu CR, Le Loarer F, Mosquera JM, Sboner A, Zhang L, Chen CL, et al. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosomes Cancer. 2013;52(8):775–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Doyle LA, Fletcher CD, Hornick JL. Nuclear expression of CAMTA1 distinguishes epithelioid hemangioendothelioma from histologic mimics. Am J Surg Pathol. 2016;40(1):94–102.

    Article  PubMed  Google Scholar 

  58. Guo T, Zhang L, Chang NE, Singer S, Maki RG, Antonescu CR. Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions. Genes Chromosomes Cancer. 2011;50(1):25–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ginter PS, Mosquera JM, MacDonald TY, D'Alfonso TM, Rubin MA, Shin SJ. Diagnostic utility of MYC amplification and anti-MYC immunohistochemistry in atypical vascular lesions, primary or radiation-induced mammary angiosarcomas, and primary angiosarcomas of other sites. Hum Pathol. 2014;45(4):709–16.

    Article  CAS  PubMed  Google Scholar 

  60. Shon W, Sukov WR, Jenkins SM, Folpe AL. MYC amplification and overexpression in primary cutaneous angiosarcoma: a fluorescence in-situ hybridization and immunohistochemical study. Mod Pathol. 2014;27(4):509–15.

    Article  CAS  PubMed  Google Scholar 

  61. Newton WA Jr, Gehan EA, Webber BL, Marsden HB, van Unnik AJ, Hamoudi AB, et al. Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification – an intergroup rhabdomyosarcoma study. Cancer. 1995;76(6):1073–85.

    Article  PubMed  Google Scholar 

  62. Rudzinski ER, Anderson JR, Chi YY, et al. Histology, fusion status, and outcome in metastatic rhabdomyosarcoma: A report from the Children’s Oncology Group. Pediatr Blood Cancer. 2017;64(12):10.1002/pbc.26645. https://doi.org/10.1002/pbc.26645.

  63. Hachitanda Y, Toyoshima S, Akazawa K, Tsuneyoshi M. N-myc gene amplification in rhabdomyosarcoma detected by fluorescence in situ hybridization: its correlation with histologic features. Mod Pathol. 1998;11(12):1222–7.

    CAS  PubMed  Google Scholar 

  64. Ragazzini P, Gamberi G, Pazzaglia L, Serra M, Magagnoli G, Ponticelli F, et al. Amplification of CDK4, MDM2, SAS and GLI genes in leiomyosarcoma, alveolar and embryonal rhabdomyosarcoma. Histol Histopathol. 2004;19(2):401–11.

    CAS  PubMed  Google Scholar 

  65. Duan F, Smith LM, Gustafson DM, Zhang C, Dunlevy MJ, Gastier-Foster JM, et al. Genomic and clinical analysis of fusion gene amplification in rhabdomyosarcoma: a report from the children’s oncology group. Genes Chromosomes Cancer. 2012;51(7):662–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Downs-Kelly E, Shehata BM, Lopez-Terrada D, Weaver J, Patel RM, Hartke M, et al. The utility of FOXO1 fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded specimens in the diagnosis of alveolar rhabdomyosarcoma. Diagn Mol Pathol. 2009;18(3):138–43.

    Article  CAS  PubMed  Google Scholar 

  67. Barr FG, Qualman SJ, Macris MH, Melnyk N, Lawlor ER, Strzelecki DM, et al. Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. Cancer Res. 2002;62(16):4704–10.

    CAS  PubMed  Google Scholar 

  68. van Gaal JC, Flucke UE, Roeffen MH, de Bont ES, Sleijfer S, Mavinkurve-Groothuis AM, et al. Anaplastic lymphoma kinase aberrations in rhabdomyosarcoma: clinical and prognostic implications. J Clin Oncol. 2012;30(3):308–15.

    Article  PubMed  CAS  Google Scholar 

  69. Wierdl M, Tsurkan L, Chi L, Hatfield MJ, Tollemar V, Bradley C, et al. Targeting ALK in pediatric RMS does not induce antitumor activity in vivo. Cancer Chemother Pharmacol. 2018;82(2):251–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rudzinski ER. Histology and fusion status in rhabdomyosarcoma. Am Soc Clin Oncol Educ Book. 2013:425–8.

    Google Scholar 

  71. Mosquera JM, Sboner A, Zhang L, Kitabayashi N, Chen CL, Sung YS, et al. Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma. Genes Chromosomes Cancer. 2013;52(6):538–50.

    Article  CAS  PubMed  Google Scholar 

  72. Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, et al. A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases. Am J Surg Pathol. 2016;40(2):224–35.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Szuhai K, de Jong D, Leung WY, Fletcher CD, Hogendoorn PC. Transactivating mutation of the MYOD1 gene is a frequent event in adult spindle cell rhabdomyosarcoma. J Pathol. 2014;232(3):300–7.

    Article  CAS  PubMed  Google Scholar 

  74. Agaram NP, Chen CL, Zhang L, LaQuaglia MP, Wexler L, Antonescu CR. Recurrent MYOD1 mutations in pediatric and adult sclerosing and spindle cell rhabdomyosarcomas: evidence for a common pathogenesis. Genes Chromosomes Cancer. 2014;53(9):779–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Martinez AP, Fritchie KJ, Weiss SW, Agaimy A, Haller F, Huang HY, et al. Histiocyte-rich rhabdomyoblastic tumor: rhabdomyosarcoma, rhabdomyoma, or rhabdomyoblastic tumor of uncertain malignant potential? A histologically distinctive rhabdomyoblastic tumor in search of a place in the classification of skeletal muscle neoplasms. Mod Pathol. 2019;32(3):446–57.

    Article  CAS  PubMed  Google Scholar 

  76. Bourgeau M, Martinez AP. Histiocyte-rich rhabdomyoblastic tumor: a report of two cases and a review of the differential diagnoses. Virchows Arch. 2021;478(2):367–73.

    Google Scholar 

  77. Fanburg-Smith JC, Miettinen M. Angiomatoid “malignant” fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype. Hum Pathol. 1999;30(11):1336–43.

    Article  CAS  PubMed  Google Scholar 

  78. Antonescu CR, Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD, et al. EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2007;46(12):1051–60.

    Article  CAS  PubMed  Google Scholar 

  79. Tanas MR, Rubin BP, Montgomery EA, Turner SL, Cook JR, Tubbs RR, et al. Utility of FISH in the diagnosis of angiomatoid fibrous histiocytoma: a series of 18 cases. Mod Pathol. 2010;23(1):93–7.

    Article  CAS  PubMed  Google Scholar 

  80. Cheah AL, Zou Y, Lanigan C, Billings SD, Rubin BP, Hornick JL, et al. ALK expression in angiomatoid fibrous histiocytoma: a potential diagnostic pitfall. Am J Surg Pathol. 2019;43(1):93–101.

    Article  PubMed  Google Scholar 

  81. Ladanyi M, Antonescu CR, Leung DH, Woodruff JM, Kawai A, Healey JH, et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res. 2002;62(1):135–40.

    CAS  PubMed  Google Scholar 

  82. Pelmus M, Guillou L, Hostein I, Sierankowski G, Lussan C, Coindre JM. Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. Am J Surg Pathol. 2002;26(11):1434–40.

    Article  PubMed  Google Scholar 

  83. Amary MF, Berisha F, Bernardi Fdel C, Herbert A, James M, Reis-Filho JS, et al. Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma. Mod Pathol. 2007;20(4):482–96.

    Article  CAS  PubMed  Google Scholar 

  84. Storlazzi CT, Mertens F, Mandahl N, Gisselsson D, Isaksson M, Gustafson P, et al. A novel fusion gene, SS18L1/SSX1, in synovial sarcoma. Genes Chromosomes Cancer. 2003;37(2):195–200.

    Article  CAS  PubMed  Google Scholar 

  85. Wang H, Jacobson A, Harmon DC, Choy E, Hornicek FJ, Raskin KA, et al. Prognostic factors in alveolar soft part sarcoma: a SEER analysis. J Surg Oncol. 2016;113(5):581–6.

    Article  PubMed  Google Scholar 

  86. Ladanyi M, Lui MY, Antonescu CR, Krause-Boehm A, Meindl A, Argani P, et al. 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. 2001;20(1):48–57.

    Article  CAS  PubMed  Google Scholar 

  87. Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003;27(6):750–61.

    Article  PubMed  Google Scholar 

  88. Enzinger FM. Clear-cell sarcoma of tendons and aponeuroses. An analysis of 21 cases. Cancer. 1965;18:1163–74.

    Article  CAS  PubMed  Google Scholar 

  89. Hisaoka M, Ishida T, Kuo TT, Matsuyama A, Imamura T, Nishida K, et al. Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol. 2008;32(3):452–60.

    Article  PubMed  Google Scholar 

  90. Panagopoulos I, Mertens F, Debiec-Rychter M, Isaksson M, Limon J, Kardas I, et al. Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses. Int J Cancer. 2002;99(4):560–7.

    Article  CAS  PubMed  Google Scholar 

  91. Park BM, Jin SA, Choi YD, Shin SH, Jung ST, Lee JB, et al. Two cases of clear cell sarcoma with different clinical and genetic features: cutaneous type with BRAF mutation and subcutaneous type with KIT mutation. Br J Dermatol. 2013;169(6):1346–52.

    Article  CAS  PubMed  Google Scholar 

  92. Enzinger FM, Shiraki M. Extraskeletal myxoid chondrosarcoma. An analysis of 34 cases. Hum Pathol. 1972;3(3):421–35.

    Article  CAS  PubMed  Google Scholar 

  93. Panagopoulos I, Mertens F, Isaksson M, Domanski HA, Brosjo O, Heim S, et al. Molecular genetic characterization of the EWS/CHN and RBP56/CHN fusion genes in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer. 2002;35(4):340–52.

    Article  CAS  PubMed  Google Scholar 

  94. Agaram NP, Zhang L, Sung YS, Singer S, Antonescu CR. Extraskeletal myxoid chondrosarcoma with non-EWSR1-NR4A3 variant fusions correlate with rhabdoid phenotype and high-grade morphology. Hum Pathol. 2014;45(5):1084–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Hisaoka M, Ishida T, Imamura T, Hashimoto H. TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer. 2004;40(4):325–8.

    Article  CAS  PubMed  Google Scholar 

  96. Urbini M, Astolfi A, Pantaleo MA, Serravalle S, Dei Tos AP, Picci P, et al. HSPA8 as a novel fusion partner of NR4A3 in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer. 2017;56(7):582–6.

    Article  CAS  PubMed  Google Scholar 

  97. Lae ME, Roche PC, Jin L, Lloyd RV, Nascimento AG. Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical, and molecular study of 32 tumors. Am J Surg Pathol. 2002;26(7):823–35.

    Article  PubMed  Google Scholar 

  98. Ladanyi M, Gerald W. Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res. 1994;54(11):2837–40.

    CAS  PubMed  Google Scholar 

  99. Neuville A, Collin F, Bruneval P, Parrens M, Thivolet F, Gomez-Brouchet A, et al. Intimal sarcoma is the most frequent primary cardiac sarcoma: clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomas. Am J Surg Pathol. 2014;38(4):461–9.

    Article  PubMed  Google Scholar 

  100. Meister P, Buckmann FW, Konrad E. Extent and level of fascial involvement in 100 cases with nodular fasciitis. Virchows Arch A Pathol Anat Histol. 1978;380(2):177–85.

    Article  CAS  PubMed  Google Scholar 

  101. Montgomery EA, Meis JM. Nodular fasciitis. Its morphologic spectrum and immunohistochemical profile. Am J Surg Pathol. 1991;15(10):942–8.

    Article  CAS  PubMed  Google Scholar 

  102. Erickson-Johnson MR, Chou MM, Evers BR, Roth CW, Seys AR, Jin L, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Investig. 2011;91(10):1427–33.

    Article  CAS  PubMed  Google Scholar 

  103. Guo R, Wang X, Chou MM, Asmann Y, Wenger DE, Al-Ibraheemi A, et al. PPP6R3-USP6 amplification: novel oncogenic mechanism in malignant nodular fasciitis. Genes Chromosomes Cancer. 2016;55(8):640–9.

    Article  CAS  PubMed  Google Scholar 

  104. Carter JM, Wang X, Dong J, Westendorf J, Chou MM, Oliveira AM. USP6 genetic rearrangements in cellular fibroma of tendon sheath. Mod Pathol. 2016;29(8):865–9.

    Article  CAS  PubMed  Google Scholar 

  105. Kao YC, Flucke U, Eijkelenboom A, Zhang L, Sung YS, Suurmeijer AJH, et al. Novel EWSR1-SMAD3 gene fusions in a group of acral fibroblastic spindle cell neoplasms. Am J Surg Pathol. 2018;42(4):522–8.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Al-Ibraheemi A, Folpe AL, Perez-Atayde AR, Perry K, Hofvander J, Arbajian E, et al. Aberrant receptor tyrosine kinase signaling in lipofibromatosis: a clinicopathological and molecular genetic study of 20 cases. Mod Pathol. 2019;32(3):423–34.

    Article  CAS  PubMed  Google Scholar 

  107. Marino-Enriquez A, Fletcher CD. Angiofibroma of soft tissue: clinicopathologic characterization of a distinctive benign fibrovascular neoplasm in a series of 37 cases. Am J Surg Pathol. 2012;36(4):500–8.

    Article  PubMed  Google Scholar 

  108. Jin Y, Moller E, Nord KH, Mandahl N, Von Steyern FV, Domanski HA, et al. Fusion of the AHRR and NCOA2 genes through a recurrent translocation t(5;8)(p15;q13) in soft tissue angiofibroma results in upregulation of aryl hydrocarbon receptor target genes. Genes Chromosomes Cancer. 2012;51(5):510–20.

    Article  CAS  PubMed  Google Scholar 

  109. Arbajian E, Magnusson L, Mertens F, Domanski HA, Vult von Steyern F, Nord KH. A novel GTF2I/NCOA2 fusion gene emphasizes the role of NCOA2 in soft tissue angiofibroma development. Genes Chromosomes Cancer. 2013;52(3):330–1.

    Article  CAS  PubMed  Google Scholar 

  110. Bekers EM, Groenen P, Verdijk MAJ, Raaijmakers-van Geloof WL, Roepman P, Vink R, et al. Soft tissue angiofibroma: Clinicopathologic, immunohistochemical and molecular analysis of 14 cases. Genes Chromosomes Cancer. 2017;56(10):750–7.

    Article  CAS  PubMed  Google Scholar 

  111. Crago AM, Denton B, Salas S, Dufresne A, Mezhir JJ, Hameed M, et al. A prognostic nomogram for prediction of recurrence in desmoid fibromatosis. Ann Surg. 2013;258(2):347–53.

    Article  PubMed  Google Scholar 

  112. Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E, et al. Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol. 2008;173(5):1518–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Miyaki M, Konishi M, Kikuchi-Yanoshita R, Enomoto M, Tanaka K, Takahashi H, et al. Coexistence of somatic and germ-line mutations of APC gene in desmoid tumors from patients with familial adenomatous polyposis. Cancer Res. 1993;53(21):5079–82.

    CAS  PubMed  Google Scholar 

  114. Dadone-Montaudie B, Alberti L, Duc A, Delespaul L, Lesluyes T, Perot G, et al. Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions. Mod Pathol. 2018;31(11):1683–93.

    Article  CAS  PubMed  Google Scholar 

  115. Enzinger FM, Smith BH. Hemangiopericytoma. An analysis of 106 cases. Hum Pathol. 1976;7(1):61–82.

    Article  CAS  PubMed  Google Scholar 

  116. Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PH. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet. 1998;18(2):184–7.

    Article  CAS  PubMed  Google Scholar 

  117. Flucke U, van Noesel MM, Wijnen M, Zhang L, Chen CL, Sung YS, et al. TFG-MET fusion in an infantile spindle cell sarcoma with neural features. Genes Chromosomes Cancer. 2017;56(9):663–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Kao YC, Fletcher CDM, Alaggio R, Wexler L, Zhang L, Sung YS, et al. Recurrent BRAF gene fusions in a subset of pediatric spindle cell sarcomas: expanding the genetic spectrum of tumors with overlapping features with infantile fibrosarcoma. Am J Surg Pathol. 2018;42(1):28–38.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Suurmeijer AJH, Dickson BC, Swanson D, Zhang L, Sung YS, Cotzia P, et al. A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Genes Chromosomes Cancer. 2018;57(12):611–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Rudzinski ER, Lockwood CM, Stohr BA, Vargas SO, Sheridan R, Black JO, et al. Pan-Trk immunohistochemistry identifies NTRK rearrangements in pediatric mesenchymal tumors. Am J Surg Pathol. 2018;42(7):927–35.

    Article  PubMed  Google Scholar 

  121. Folpe AL, Lane KL, Paull G, Weiss SW. Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes: a clinicopathologic study of 73 cases supporting their identity and assessing the impact of high-grade areas. Am J Surg Pathol. 2000;24(10):1353–60.

    Article  CAS  PubMed  Google Scholar 

  122. Mertens F, Fletcher CD, Antonescu CR, Coindre JM, Colecchia M, Domanski HA, et al. Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Lab Investig. 2005;85(3):408–15.

    Article  CAS  PubMed  Google Scholar 

  123. Lau PP, Lui PC, Lau GT, Yau DT, Cheung ET, Chan JK. EWSR1-CREB3L1 gene fusion: a novel alternative molecular aberration of low-grade fibromyxoid sarcoma. Am J Surg Pathol. 2013;37(5):734–8.

    Article  PubMed  Google Scholar 

  124. Doyle LA, Moller E, Dal Cin P, Fletcher CD, Mertens F, Hornick JL. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol. 2011;35(5):733–41.

    Article  PubMed  Google Scholar 

  125. Meis-Kindblom JM, Kindblom LG, Enzinger FM. Sclerosing epithelioid fibrosarcoma. A variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol. 1995;19(9):979–93.

    Article  CAS  PubMed  Google Scholar 

  126. Arbajian E, Puls F, Magnusson L, Thway K, Fisher C, Sumathi VP, et al. Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma. Am J Surg Pathol. 2014;38(6):801–8.

    Article  PubMed  Google Scholar 

  127. Dewaele B, Libbrecht L, Levy G, Brichard B, Vanspauwen V, Sciot R, et al. A novel EWS-CREB3L3 gene fusion in a mesenteric sclerosing epithelioid fibrosarcoma. Genes Chromosomes Cancer. 2017;56(9):695–9.

    Article  CAS  PubMed  Google Scholar 

  128. Arbajian E, Puls F, Antonescu CR, Amary F, Sciot R, Debiec-Rychter M, et al. In-depth genetic analysis of sclerosing epithelioid fibrosarcoma reveals recurrent genomic alterations and potential treatment targets. Clin Cancer Res. 2017;23(23):7426–34.

    Article  CAS  PubMed  Google Scholar 

  129. Doyle LA, Wang WL, Dal Cin P, Lopez-Terrada D, Mertens F, Lazar AJ, et al. MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with FUS gene rearrangement. Am J Surg Pathol. 2012;36(10):1444–51.

    Article  PubMed  Google Scholar 

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  1. Department of Pathology and Laboratory Medicine, Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA

    Anthony P. Martinez

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  1. Department of Laboratory Medicine, Geisinger Health, Danville, PA, USA

    Yi Ding

  2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Linsheng Zhang

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Martinez, A.P. (2021). Soft Tissue Tumors. In: Ding, Y., Zhang, L. (eds) Practical Oncologic Molecular Pathology. Practical Anatomic Pathology. Springer, Cham. https://doi.org/10.1007/978-3-030-73227-1_10

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