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Diagnosis and Treatment of Myxoid Liposarcomas: Histology Matters

  • Sarah Abaricia
  • Angela C. HirbeEmail author
Sarcoma (SH Okuno, Section Editor)
  • 153 Downloads
Part of the following topical collections:
  1. Topical Collection on Sarcoma

Opinion statement

Sarcomas are a heterogeneous group of rare malignancies that arise from mesenchymal cells and can occur anywhere in the body. Herein, the focus will be on one subtype of sarcoma that arises from adipocytic tissue, liposarcoma. Specifically, the review will focus on one type of liposarcoma, myxoid liposarcoma. Given the rarity of this tumor, it is imperative that these patients are treated at a sarcoma center, where a multidisciplinary approach incorporates all the modalities available including clinical trials. As the understanding of the biology of myxoid liposarcomas progresses, more targeted therapies are being developed that will lead to better tolerated treatments and improved survival for patients. In this review, we will be discussing the pathophysiology, clinical presentation, diagnostic workup, and available treatment options including surgery, radiation, chemotherapy, and clinical trials.

Keywords

Myxoid liposarcoma Treatments Staging Pathology 

Notes

Compliance with Ethical Standards

Conflict of Interest

Sarah Abaricia and Angela C. Hirbe declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Hui JY. Epidemiology and etiology of sarcomas. Surg Clin North Am. 2016;96(5):901–14.  https://doi.org/10.1016/j.suc.2016.05.005.CrossRefPubMedGoogle Scholar
  2. 2.
    Burningham Z, Hashibe M, Spector L, Schiffman JD. The epidemiology of sarcoma. Clin Sarcoma Res. 2012;2(1):14.  https://doi.org/10.1186/2045-3329-2-14.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.  https://doi.org/10.3322/caac.21442.CrossRefGoogle Scholar
  4. 4.
    Guan Z, Yu X, Wang H, Wang H, Zhang J, Li G, et al. Advances in the targeted therapy of liposarcoma. Onco Targets Ther. 2015;8:125–36.  https://doi.org/10.2147/OTT.S72722.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lee ATJ, Thway K, Huang PH, Jones RL. Clinical and molecular spectrum of liposarcoma. J Clin Oncol. 2018;36(2):151–9.  https://doi.org/10.1200/JCO.2017.74.9598.CrossRefPubMedGoogle Scholar
  6. 6.
    Crago AM, Dickson MA. Liposarcoma: multimodality management and future targeted therapies. Surg Oncol Clin N Am. 2016;25(4):761–73.  https://doi.org/10.1016/j.soc.2016.05.007.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Fiore M, Grosso F, Lo Vullo S, Pennacchioli E, Stacchiotti S, Ferrari A, et al. Myxoid/round cell and pleomorphic liposarcomas: prognostic factors and survival in a series of patients treated at a single institution. Cancer. 2007;109(12):2522–31.  https://doi.org/10.1002/cncr.22720.CrossRefPubMedGoogle Scholar
  8. 8.
    Hoffman A, Ghadimi MP, Demicco EG, Creighton CJ, Torres K, Colombo C, et al. Localized and metastatic myxoid/round cell liposarcoma: clinical and molecular observations. Cancer. 2013;119(10):1868–77.  https://doi.org/10.1002/cncr.27847.CrossRefPubMedGoogle Scholar
  9. 9.
    ten Heuvel SE, Hoekstra HJ, van Ginkel RJ, Bastiaannet E, Suurmeijer AJ. Clinicopathologic prognostic factors in myxoid liposarcoma: a retrospective study of 49 patients with long-term follow-up. Ann Surg Oncol. 2007;14(1):222–9.  https://doi.org/10.1245/s10434-006-9043-7.CrossRefPubMedGoogle Scholar
  10. 10.
    Tateishi U, Hasegawa T, Beppu Y, Kawai A, Satake M, Moriyama N. Prognostic significance of MRI findings in patients with myxoid-round cell liposarcoma. AJR Am J Roentgenol. 2004;182(3):725–31.  https://doi.org/10.2214/ajr.182.3.1820725.CrossRefPubMedGoogle Scholar
  11. 11.
    Lowenthal D, Zeile M, Niederhagen M, Fehlberg S, Schnapauff D, Pink D, et al. Differentiation of myxoid liposarcoma by magnetic resonance imaging: a histopathologic correlation. Acta Radiol. 2014;55(8):952–60.  https://doi.org/10.1177/0284185113508114.CrossRefPubMedGoogle Scholar
  12. 12.
    Pohlig F, Kirchhoff C, Lenze U, Schauwecker J, Burgkart R, Rechl H, et al. Percutaneous core needle biopsy versus open biopsy in diagnostics of bone and soft tissue sarcoma: a retrospective study. Eur J Med Res. 2012;17:29.  https://doi.org/10.1186/2047-783X-17-29.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Skrzynski MC, Biermann JS, Montag A, Simon MA. Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J Bone Joint Surg Am. 1996;78(5):644–9.CrossRefGoogle Scholar
  14. 14.
    Ray-Coquard I, Ranchere-Vince D, Thiesse P, Ghesquieres H, Biron P, Sunyach MP, et al. Evaluation of core needle biopsy as a substitute to open biopsy in the diagnosis of soft-tissue masses. Eur J Cancer. 2003;39(14):2021–5.CrossRefGoogle Scholar
  15. 15.
    Strauss DC, Qureshi YA, Hayes AJ, Thway K, Fisher C, Thomas JM. The role of core needle biopsy in the diagnosis of suspected soft tissue tumours. J Surg Oncol. 2010;102(5):523–9.  https://doi.org/10.1002/jso.21600.CrossRefPubMedGoogle Scholar
  16. 16.
    Heslin MJ, Lewis JJ, Woodruff JM, Brennan MF. Core needle biopsy for diagnosis of extremity soft tissue sarcoma. Ann Surg Oncol. 1997;4(5):425–31.CrossRefGoogle Scholar
  17. 17.
    Schmidt H, Bartel F, Kappler M, Wurl P, Lange H, Bache M, et al. Gains of 13q are correlated with a poor prognosis in liposarcoma. Mod Pathol. 2005;18(5):638–44.  https://doi.org/10.1038/modpathol.3800326.CrossRefPubMedGoogle Scholar
  18. 18.
    Suzuki K, Matsui Y, Endo K, Kubo T, Hasegawa T, Kimura T, et al. Myxoid liposarcoma with EWS-CHOP type 1 fusion gene. Anticancer Res. 2010;30(11):4679–83.PubMedGoogle Scholar
  19. 19.
    Powers MP, Wang WL, Hernandez VS, Patel KS, Lev DC, Lazar AJ, et al. Detection of myxoid liposarcoma-associated FUS-DDIT3 rearrangement variants including a newly identified breakpoint using an optimized RT-PCR assay. Mod Pathol. 2010;23(10):1307–15.  https://doi.org/10.1038/modpathol.2010.118.CrossRefPubMedGoogle Scholar
  20. 20.
    Bode-Lesniewska B, Frigerio S, Exner U, Abdou MT, Moch H, Zimmermann DR. Relevance of translocation type in myxoid liposarcoma and identification of a novel EWSR1-DDIT3 fusion. Genes Chromosomes Cancer. 2007;46(11):961–71.  https://doi.org/10.1002/gcc.20478.CrossRefPubMedGoogle Scholar
  21. 21.
    Moreau LC, Turcotte R, Ferguson P, Wunder J, Clarkson P, Masri B, et al. Myxoid/round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases. Ann Surg Oncol. 2012;19(4):1081–8.  https://doi.org/10.1245/s10434-011-2127-z.CrossRefPubMedGoogle Scholar
  22. 22.
    Chung PW, Deheshi BM, Ferguson PC, Wunder JS, Griffin AM, Catton CN, et al. Radiosensitivity translates into excellent local control in extremity myxoid liposarcoma: a comparison with other soft tissue sarcomas. Cancer. 2009;115(14):3254–61.  https://doi.org/10.1002/cncr.24375.CrossRefPubMedGoogle Scholar
  23. 23.
    Morton DL, Eilber FR, Townsend CM Jr, Grant TT, Mirra J, Weisenburger TH. Limb salvage from a multidisciplinary treatment approach for skeletal and soft tissue sarcomas of the extremity. Ann Surg. 1976;184(3):268–78.CrossRefGoogle Scholar
  24. 24.
    Rosenberg SA, Tepper J, Glatstein E, Costa J, Baker A, Brennan M, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg. 1982;196(3):305–15.CrossRefGoogle Scholar
  25. 25.
    Trovik CS, Bauer HC, Alvegard TA, Anderson H, Blomqvist C, Berlin O, et al. Surgical margins, local recurrence and metastasis in soft tissue sarcomas: 559 surgically-treated patients from the Scandinavian Sarcoma Group Register. Eur J Cancer. 2000;36(6):710–6.CrossRefGoogle Scholar
  26. 26.
    Gronchi A, Casali PG, Mariani L, Miceli R, Fiore M, Lo Vullo S, et al. Status of surgical margins and prognosis in adult soft tissue sarcomas of the extremities: a series of patients treated at a single institution. J Clin Oncol. 2005;23(1):96–104.  https://doi.org/10.1200/JCO.2005.04.160.CrossRefPubMedGoogle Scholar
  27. 27.
    Stojadinovic A, Leung DH, Hoos A, Jaques DP, Lewis JJ, Brennan MF. Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas. Ann Surg. 2002;235(3):424–34.CrossRefGoogle Scholar
  28. 28.
    Zagars GK, Goswitz MS, Pollack A. Liposarcoma: outcome and prognostic factors following conservation surgery and radiation therapy. Int J Radiat Oncol Biol Phys. 1996;36(2):311–9.CrossRefGoogle Scholar
  29. 29.
    Pitson G, Robinson P, Wilke D, Kandel RA, White L, Griffin AM, et al. Radiation response: an additional unique signature of myxoid liposarcoma. Int J Radiat Oncol Biol Phys. 2004;60(2):522–6.  https://doi.org/10.1016/j.ijrobp.2004.03.009.CrossRefPubMedGoogle Scholar
  30. 30.
    O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359(9325):2235–41.  https://doi.org/10.1016/S0140-6736(02)09292-9.CrossRefPubMedGoogle Scholar
  31. 31.
    Cheng EY, Dusenbery KE, Winters MR, Thompson RC. Soft tissue sarcomas: preoperative versus postoperative radiotherapy. J Surg Oncol. 1996;61(2):90–9.  https://doi.org/10.1002/(SICI)1096-9098(199602)61:2<90::AID-JSO2>3.0.CO;2-M.CrossRefPubMedGoogle Scholar
  32. 32.
    Eilber FC, Brennan MF, Eilber FR, Dry SM, Singer S, Kattan MW. Validation of the postoperative nomogram for 12-year sarcoma-specific mortality. Cancer. 2004;101(10):2270–5.  https://doi.org/10.1002/cncr.20570.CrossRefPubMedGoogle Scholar
  33. 33.
    Pasquali S, Colombo C, Bottelli S, Verderio P, Broto JM, Lopez-Pousa A, et al. The sarculator stratified prognosis of patients with high-risk soft tissue sarcomas (STS) of extremities and trunk wall treated with perioperative chemotherapy in a randomised controlled trial (RCT). J Clin Oncol. 2017;35(15_suppl):11016.  https://doi.org/10.1200/JCO.2017.35.15_suppl.11016.CrossRefGoogle Scholar
  34. 34.
    Frustaci S, Gherlinzoni F, De Paoli A, Bonetti M, Azzarelli A, Comandone A, et al. Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol. 2001;19(5):1238–47.  https://doi.org/10.1200/JCO.2001.19.5.1238.CrossRefPubMedGoogle Scholar
  35. 35.
    Schenone AD, Luo J, Montgomery L, Morgensztern D, Adkins DR, Van Tine BA. Risk-stratified patients with resectable soft tissue sarcoma benefit from epirubicin-based adjuvant chemotherapy. Cancer Med. 2014;3(3):603–12.  https://doi.org/10.1002/cam4.209.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Gronchi A, Frustaci S, Mercuri M, Martin J, Lopez-Pousa A, Verderio P, et al. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012;30(8):850–6.  https://doi.org/10.1200/JCO.2011.37.7218.CrossRefPubMedGoogle Scholar
  37. 37.
    Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017;18(6):812–22.  https://doi.org/10.1016/S1470-2045(17)30334-0.CrossRefPubMedGoogle Scholar
  38. 38.
    Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993;11(7):1269–75.  https://doi.org/10.1200/JCO.1993.11.7.1269.CrossRefPubMedGoogle Scholar
  39. 39.
    Blum RH, Edmonson J, Ryan L, Pelletier L. Efficacy of ifosfamide in combination with doxorubicin for the treatment of metastatic soft-tissue sarcoma. The Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 1993;31(Suppl 2):S238–40.PubMedGoogle Scholar
  40. 40.
    •• Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388(10043):488–97.  https://doi.org/10.1016/S0140-6736(16)30587-6. Clinical trial that established new standard of care with adriamycin and olaratumab as the trial showed a vastly superior median overall survival with dual combination versus adriamycin alone. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, Tavecchio M, et al. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther. 2009;8(2):449–57.  https://doi.org/10.1158/1535-7163.MCT-08-0848.CrossRefPubMedGoogle Scholar
  42. 42.
    • Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, et al. Efficacy and safety of trabectedin or dacarbazine for metastatic Liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016;34(8):786–93.  https://doi.org/10.1200/JCO.2015.62.4734. Trabectedin was FDA-approved as second-line therapy following this clinical trial revealing decreased risk of progression compared to dacarbazine.CrossRefPubMedGoogle Scholar
  43. 43.
    Barone A, Chi DC, Theoret MR, Chen H, He K, Kufrin D, et al. FDA approval summary: trabectedin for unresectable or metastatic liposarcoma or leiomyosarcoma following an anthracycline-containing regimen. Clin Cancer Res. 2017;23(24):7448–53.  https://doi.org/10.1158/1078-0432.CCR-17-0898.CrossRefPubMedGoogle Scholar
  44. 44.
    Koliou P, Karavasilis V, Theochari M, Pollack SM, Jones RL, Thway K. Advances in the treatment of soft tissue sarcoma: focus on eribulin. Cancer Manag Res. 2018;10:207–16.  https://doi.org/10.2147/CMAR.S143019.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Singhi EK, Moore DC, Muslimani A. Metastatic soft tissue sarcomas: a review of treatment and new pharmacotherapies. P T. 2018;43(7):410–29.PubMedPubMedCentralGoogle Scholar
  46. 46.
    • Demetri GD, Schoffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, et al. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017;35(30):3433–9.  https://doi.org/10.1200/JCO.2016.71.6605. Eribulin was FDA-approved for second-line treatment following this trial showing an improvement in overall survivial as well as progression-free survival compared to dacarbazine. CrossRefPubMedGoogle Scholar
  47. 47.
    van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829):1879–86.  https://doi.org/10.1016/S0140-6736(12)60651-5.CrossRefPubMedGoogle Scholar
  48. 48.
    Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schoffski P, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC study 62043). J Clin Oncol. 2009;27(19):3126–32.  https://doi.org/10.1200/JCO.2008.21.3223.CrossRefPubMedGoogle Scholar
  49. 49.
    Agulnik M, Mohindra NA, Milhem MM, Attia S, Robinson SI, Rademaker A, et al. A phase II study of pazopanib with oral topotecan in patients with metastatic and non-resectable soft tissue and bone sarcomas. J Clin Oncol, 2018 ASCO Annual Meeting. 2018;36((suppl; abstr 11550)).Google Scholar
  50. 50.
    Mahmood ST, Agresta S, Vigil CE, Zhao X, Han G, D'Amato G, et al. Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma. Int J Cancer. 2011;129(8):1963–9.  https://doi.org/10.1002/ijc.25843.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Charytonowicz E, Terry M, Coakley K, Telis L, Remotti F, Cordon-Cardo C, et al. PPARgamma agonists enhance ET-743-induced adipogenic differentiation in a transgenic mouse model of myxoid round cell liposarcoma. J Clin Invest. 2012;122(3):886–98.  https://doi.org/10.1172/JCI60015.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Takeuchi A, Yamamoto N, Shirai T, Hayashi K, Miwa S, Munesue S, et al. Clinical relevance of peroxisome proliferator-activated receptor-gamma expression in myxoid liposarcoma. BMC Cancer. 2016;16:442.  https://doi.org/10.1186/s12885-016-2524-6.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Tontonoz P, Singer S, Forman BM, Sarraf P, Fletcher JA, Fletcher CD, et al. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc Natl Acad Sci U S A. 1997;94(1):237–41.CrossRefGoogle Scholar
  54. 54.
    Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, et al. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999;96(7):3951–6.CrossRefGoogle Scholar
  55. 55.
    Pishvaian MJ, Marshall JL, Wagner AJ, Hwang JJ, Malik S, Cotarla I, et al. A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies. Cancer. 2012;118(21):5403–13.  https://doi.org/10.1002/cncr.27526.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Smith SM, Iwenofu OH. NY-ESO-1: a promising cancer testis antigen for sarcoma immunotherapy and diagnosis. Chin Clin Oncol. 2018;7(4):44.  https://doi.org/10.21037/cco.2018.08.11.CrossRefPubMedGoogle Scholar
  57. 57.
    Shurell E, Vergara-Lluri ME, Li Y, Crompton JG, Singh A, Bernthal N, et al. Comprehensive adipocytic and neurogenic tissue microarray analysis of NY-ESO-1 expression - a promising immunotherapy target in malignant peripheral nerve sheath tumor and liposarcoma. Oncotarget. 2016;7(45):72860–7.  https://doi.org/10.18632/oncotarget.12096.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Pollack SM, Jungbluth AA, Hoch BL, Farrar EA, Bleakley M, Schneider DJ, et al. NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. Cancer. 2012;118(18):4564–70.  https://doi.org/10.1002/cncr.27446.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Svec D, Dolatabadi S, Thomsen C, Cordes N, Shannon M, Fitzpatrick P, et al. Identification of inhibitors regulating cell proliferation and FUS-DDIT3 expression in myxoid liposarcoma using combined DNA, mRNA, and protein analyses. Lab Investig. 2018;98(7):957–67.  https://doi.org/10.1038/s41374-018-0046-3.CrossRefPubMedGoogle Scholar
  60. 60.
    Tornin J, Hermida-Prado F, Padda RS, Gonzalez MV, Alvarez-Fernandez C, Rey V, et al. FUS-CHOP promotes invasion in myxoid liposarcoma through a SRC/FAK/RHO/ROCK-dependent pathway. Neoplasia. 2018;20(1):44–56.  https://doi.org/10.1016/j.neo.2017.11.004.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Medical OncologyWashington University School of MedicineSt. LouisUSA
  2. 2.Siteman Cancer CenterWashington University School of MedicineSaint LouisUSA

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