Virchows Archiv

, Volume 456, Issue 2, pp 167–179 | Cite as

Well-differentiated and dedifferentiated liposarcomas

  • Jean-Michel CoindreEmail author
  • Florence Pédeutour
  • Alain Aurias
Review and Perspective


Atypical lipomatous tumor or well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) share the same basic genetic abnormality characterized by a simple genomic profile with a 12q14–15 amplification involving MDM2 gene. These tumors are the most frequent LPS. This paper reviews the molecular pathology, general clinical and imaging features, histopathology, new diagnostic tools, and prognosis of ALT-WDLPS and DDLPS.


Well-differentiated liposarcoma Dedifferentiated liposarcoma MDM2 CDK4 


  1. 1.
    Fletcher CDM, Unni KK, Mertens F (2002) Pathology and genetics. Tumours of soft tissue and bone. IARC, LyonGoogle Scholar
  2. 2.
    Idbaih A, Coindre JM, Derré J et al (2005) Myxoid malignant fibrous histiocytoma and pleomorphic liposarcoma share very similar genomic imbalances. Lab Invest 85:176–181CrossRefPubMedGoogle Scholar
  3. 3.
    Willems SM, Debiec-Rychter M, Szuhai K et al (2006) Local recurrence of myxofibrosarcoma is associated with increase in tumour grade and cytogenetic aberrations, suggesting a multistep tumour progression model. Mod Pathol 19:407–416CrossRefPubMedGoogle Scholar
  4. 4.
    Rubin BP, Fletcher CDM (1997) The cytologenetics of lipomatous tumours. Histopathology 30:507–511CrossRefPubMedGoogle Scholar
  5. 5.
    Pedeutour F, Marie G, Sirvent N (2004) De la cytogénétique à la cytogénomique des tumeurs adipocytaires. 2. Tumeurs adipocytaires malignes. Bull Cancer 91:317–323PubMedGoogle Scholar
  6. 6.
    Sandberg AA (2004) Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma. Cancer Genet Cytogenet 155:1–24CrossRefPubMedGoogle Scholar
  7. 7.
    Pedeutour F, Suijkerbuijk RF, Forus A et al (1994) Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcomas. Genes Chromosomes Cancer 10:85–94CrossRefPubMedGoogle Scholar
  8. 8.
    Italiano A, Blanchini L, Keslair F et al (2008) HMGA2 is the partner of MDM2 in well-differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a distinctive inconsistent amplicon. Int J Cancer 122:2233–2241CrossRefPubMedGoogle Scholar
  9. 9.
    Sirvent N, Forus A, Lescaut W et al (2000) Characterization of centromere alterations in liposarcomas. Genes Chromosomes Cancer 29:117–129CrossRefPubMedGoogle Scholar
  10. 10.
    Pedeutour F, Forus A, Coindre JM et al (1999) Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 24:30–41CrossRefPubMedGoogle Scholar
  11. 11.
    Italiano A, Maire G, Sirvent N et al (2009) Variability of origin for the neocentromeric sequences in analphoid supernumerary marker chromosomes of well-differentiated liposarcomas. Cancer Lett 273:323–330CrossRefPubMedGoogle Scholar
  12. 12.
    Sirvent N, Coindre JM, Marie G et al (2007) 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 31:1476–1489CrossRefPubMedGoogle Scholar
  13. 13.
    Bui Nguyen Binh M, Sastre-Garau X, Guillou L et al (2005) MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes. A comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol 29:1340–1347CrossRefGoogle Scholar
  14. 14.
    Chibon F, Mariani O, Derré J et al (2002) A subgroup of malignant fibrous histiocytomas in associated with genetic changes similar to those of well-differentiated liposarcomas. Cancer Genet Cytogenet 139:24–29CrossRefPubMedGoogle Scholar
  15. 15.
    Mariani O, Brennetot C, Coindre JM et al (2007) JUN oncogene amplification and overexpression block adipocytic differentiation in highly aggressive sarcomas. Cancer Cell 11:361–374CrossRefPubMedGoogle Scholar
  16. 16.
    Chibon F, Mariani O, Derré J et al (2004) ASKI (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14–15 and 6q23 amplifications. Genes Chromosomes Cancer 40:32–37CrossRefPubMedGoogle Scholar
  17. 17.
    Momand J, Wu HH, Dasgupta G (2000) MDM2-master regulator of the p53 tumor suppressor protein. Gene 242:15–29CrossRefPubMedGoogle Scholar
  18. 18.
    Ortega S, Malumbres M, Barbacid M (2002) Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta 1602:73–87PubMedGoogle Scholar
  19. 19.
    Castriota G, Thompson GM, Lin Y et al (2007) Peroxisome proliferator-activited receptor gamma agonists inhibit adipocyte expression of alpha1-acid glycoprotein. Cell Biol Int 31:586–591CrossRefPubMedGoogle Scholar
  20. 20.
    Singer S, Socci ND, Ambrosini G et al (2007) Gene expression profiling of liposarcoma identifies distinct biological types/subtypes and potential therapeutic targets in well-differentiated and dedifferentiated liposarcoma. Cancer Res 67:6626–6636CrossRefPubMedGoogle Scholar
  21. 21.
    Müller CR, Paulsen EB, Noordhuis P et al (2007) Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A. Int J Cancer 121:199–205CrossRefPubMedGoogle Scholar
  22. 22.
    Shapiro GI (2006) Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 24:1770–1783CrossRefPubMedGoogle Scholar
  23. 23.
    Cuadrado A, Gnozalez L, Suarez Y et al (2004) JNK activation is critical for Aplidin-induced apoptosis. Oncogene 23:4673–4680CrossRefPubMedGoogle Scholar
  24. 24.
    Dei Tos AP, Pedeutour F (2002) Atypical lipomatous tumour/well differentiated liposarcoma. In: Fletcher CDM, Unni KK, Mertens F (eds) Pathology and Genetics. Tumours of soft tissue and bone. IARC, Lyon, pp 35–37Google Scholar
  25. 25.
    Pilotti S, Della Torre G, Mezzelani A et al (2000) The expression of MDM2/CDK4 gene product in the differential diagnosis of well differentiated liposarcoma and large deep-seated lipoma. Br J Cancer 82:1271–1275CrossRefPubMedGoogle Scholar
  26. 26.
    Dalal KM, Kattan MW, Antonescu CR et al (2006) Subtype specific prognostic nomogram for patients with primary liposarcoma of the retroperitoneum, extremity, or trunk. Ann Surg 244:381–391PubMedGoogle Scholar
  27. 27.
    Weiss SW, Goldblum JR (2008) Liposarcoma. In: Weiss SW, Goldblum JR (eds) Enzinger and Weiss’s soft tissue tumors. Mosby, St Louis, pp 477–516Google Scholar
  28. 28.
    Kraus MD, Guillou L, Fletcher CD (1997) Well-differentiated inflammatory liposarcoma: an uncommon and easily overlooked variant of a common sarcoma. Am J Surg Pathol 1:37–50Google Scholar
  29. 29.
    Weaver J, Downs-Kelly E, Goldblum JR et al (2008) Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol 21:943–949CrossRefPubMedGoogle Scholar
  30. 30.
    Evans HL, Soule EH, Winkelman RK (1979) Atypical lipoma, atypical intramuscular lipoma, and well differentiated retroperitoneal liposarcoma. Cancer 43:574CrossRefPubMedGoogle Scholar
  31. 31.
    Azumi N, Curtis J, Kempson RL et al (1987) Atypical and malignant neoplasms showing lipomatous differentiation: a study of 111 cases. Am J Surg Pathol 11:161CrossRefPubMedGoogle Scholar
  32. 32.
    Weiss SW, Rao VK (1992) Well-differentiated liposarcoma (atypical lipoma) of deep soft tissue of the extremities, retroperitoneum and miscellaneous sites: a follow-up study of 92 cases with analysis of the incidence of "dedifferentiated". Am J Surg Pathol 16:1051CrossRefPubMedGoogle Scholar
  33. 33.
    Evans HL (1979) Liposarcoma: a study of 55 cases with a reassessment of its classification. Am J Surg Pathol 3:507–523PubMedCrossRefGoogle Scholar
  34. 34.
    Henricks WH, Chu YC, Goldblum JR et al (1997) Dedifferentiated liposarcoma. A clinicopathologic analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol 21:271–281CrossRefPubMedGoogle Scholar
  35. 35.
    McCormick D, Mentzel T, Beham A et al (1994) Dedifferentiated liposarcoma. Clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas. Am J Surg Pathol 18:1213–1223PubMedGoogle Scholar
  36. 36.
    Dalal KM, Kattan MW, Antonescu CR et al (2006) Subtype specific prognostic nomogram for patients with primary liposarcoma of the retroperitoneum, extremity, or trunk. Ann Surg 244:381–391PubMedGoogle Scholar
  37. 37.
    Dei Tos AP, Pedeutour F (2002) Dedifferentiated liposarcoma. In: Fletcher CDM, Unni KK, Mertens F (eds) Pathology and genetics—tumours of soft tissue and bone. IARC, Lyon, pp 38–39Google Scholar
  38. 38.
    Coindre JM, Mariani O, Chibon F et al (2003) Most malignant fibrous histiocytomas developed in the retroperitoneum are dedifferentiated liposarcomas: a review of 25 cases initially diagnosed as malignant fibrous histiocytoma. Mod Pathol 16:256–262CrossRefPubMedGoogle Scholar
  39. 39.
    Coindre JM, Hostein I, Maire G et al (2004) Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity. J Pathol 203:822–830CrossRefPubMedGoogle Scholar
  40. 40.
    Tallini G, Erlandson RA, Brennan MF et al (1993) Divergent myosarcomatous differentiation in retroperitoneal liposarcoma. Am J Surg Pathol 17:546–556CrossRefPubMedGoogle Scholar
  41. 41.
    Evans HL, Khurana KK, Kemp BL et al (1994) Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma. Am J Surg Pathol 18:1150–1157PubMedGoogle Scholar
  42. 42.
    Bui Nguyen Binh M, Guillou L, Hostein I et al (2007) Dedifferentiated liposarcomas with divergent myosarcomatous differentiation developed in the internal trunk. A study of 27 cases and comparison to conventional dedifferentiated liposarcomas and leiomyosarcomas. Am J Surg Pathol 31:1557–1566CrossRefPubMedGoogle Scholar
  43. 43.
    Fanburg-Smith JC, Miettinen M (1998) Liposarcoma with meningothelial-like whorls: a study of 17 cases of a distinctive histological pattern associated with dedifferentiated liposarcoma. Histopathological 33:414–424CrossRefGoogle Scholar
  44. 44.
    Nascimento AG, Kurtin PJ, Guillou L et al (1998) Dedifferentiated liposarcoma: a report of nine cases with a peculiar neurolike whorling pattern associated with metaplastic bone formation. Am J Surg Pathol 22:945–955CrossRefPubMedGoogle Scholar
  45. 45.
    Willems SW, Szuhai K, Hartgrink H et al (2007) CT-guided, COBRA-FISH-assisted diagnosis of well-differentiated liposarcoma (inflammatory subtype) of the retroperitoneum. Histopathology 51:422–426CrossRefPubMedGoogle Scholar
  46. 46.
    Mussi C, Collini P, Miceli R et al (2008) The prognostic impact of dedifferentiation in retroperitoneal liposarcoma: a series of surgically treated patients at a single institution. Cancer 113:1657–1665CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jean-Michel Coindre
    • 1
    • 2
    • 5
    Email author
  • Florence Pédeutour
    • 3
  • Alain Aurias
    • 4
  1. 1.Department of Pathology and INSERM U916Institut BergoniéBordeauxFrance
  2. 2.Laboratory of PathologyUniversity Victor SégalenBordeauxFrance
  3. 3.Laboratoire de Génétique Somatique des Tumeurs SolidesCHU de Nice et CNRS UMR 6543, Faculté de MédecineNiceFrance
  4. 4.Genetics and Biology of Cancers and INSERM U830Institut CurieParisFrance
  5. 5.Department of PathologyInstitut BergoniéBordeaux CédexFrance

Personalised recommendations