Undifferentiated/Unclassified Sarcoma

  • A. Shah
  • R. Botchu
  • A. M. Davies
  • S. L. JamesEmail author


Soft tissue sarcomas (STSs) represent a broad and complex group of mesenchymal lesions with a range of differentiation. The current 2013 World Health Organisation (WHO) classification of soft tissue tumours (Fletcher et al., WHO classification of tumours of soft tissue and bone IARC Press; Lyon, 2013) reflects the better understanding gained with advances in immunohistochemical analysis and cytogenetic and molecular genetic characterisation of STSs. There are over 50 subtypes of STS (Reichardt P, Future Oncol 10:s19–27, 2014).

Malignant fibrous histiocytoma (MFH) was originally used to describe a group of pleomorphic spindle cell tumours that demonstrated both fibroblastic and histiocytic differentiation. Further analysis has not revealed a true histiocytic differentiation. Some STSs that were previously called MFH can now be subclassified in light of the significant developments in molecular analysis. However, a small subset of sarcomas cannot be classified into any presently defined categories, as no identifiable line of differentiation can be found (Lehnhardt et al., J Surg Oncol 97:40–43, 2008). The term MFH has been abandoned and is now replaced with the term ‘undifferentiated pleomorphic sarcoma (UPS)’. Despite this reclassification, the diagnosis of undifferentiated soft tissue sarcoma (USTS) remains controversial with some centres still using the term MFH. USTSs are now described in this entirely new category. It should be noted that dedifferentiated subtypes of specific STSs are not included in this group.


Synovial Sarcoma Malignant Fibrous Histiocytoma Ewing Sarcoma Epithelioid Sarcoma Myositis Ossificans 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Alaggio R, Bisogno G, Rosato A et al (2009) Undifferentiated sarcoma: does it exist? A clinicopathologic study of 7 pediatric cases and review of literature. Hum Pathol 40:1600–1610CrossRefPubMedGoogle Scholar
  2. 2.
    Alaggio R, Ninfo V, Rosolen A et al (2006) Primitive myxoid mesenchymal tumor of infancy: a clinicopathologic report of 6 cases. Am J Surg Pathol 30:388–394CrossRefPubMedGoogle Scholar
  3. 3.
    Carneiro A, Francis P, Bendahl PO et al (2009) Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin? Lab Invest J Tech Methods Pathol 89:668–675CrossRefGoogle Scholar
  4. 4.
    Chan CY, Janarthan N, Vivek AS et al (2008) The outcome of pleomorphic sarcoma at University Malaya Medical Center – a fifteen-year review. Med J Malaysia 63:311–314PubMedGoogle Scholar
  5. 5.
    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
  6. 6.
    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. Modern Pathol Off J US Can Acad Pathol, Inc 16:256–262Google Scholar
  7. 7.
    Cong Z, Gong J (2011) Primary malignant fibrous histiocytoma of the liver: CT findings in five histopathological proven patients. Abdom Imaging 36:552–556CrossRefPubMedGoogle Scholar
  8. 8.
    Constantinidou A, Pollack S, Loggers E et al (2013) The evolution of systemic therapy in sarcoma. Expert Rev Anticancer Ther 13:211–223CrossRefPubMedGoogle Scholar
  9. 9.
    Dei Tos AP (2006) Classification of pleomorphic sarcomas: where are we now? Histopathology 48:51–62CrossRefPubMedGoogle Scholar
  10. 10.
    Delisca GO, Mesko NW, Alamanda VK et al (2015) MFH and high-grade undifferentiated pleomorphic sarcoma-what’s in a name? J Surg Oncol 111:173–177CrossRefPubMedGoogle Scholar
  11. 11.
    Eriksson M (2010) Histology-driven chemotherapy of soft-tissue sarcoma. Ann Oncol Off J Eur Soc Med Oncol/ESMO 21(Suppl 7):vii270–vii276Google Scholar
  12. 12.
    Faizi NA, Thulkar S, Sharma R et al (2012) Magnetic resonance imaging and positron emission tomography-computed tomography evaluation of soft tissue sarcoma with surgical and histopathological correlation. Indian J Nucl Med IJNM Off J Soc Nucl Med, India 27:213–220Google Scholar
  13. 13.
    Fletcher CD (2006) The evolving classification of soft tissue tumours: an update based on the new WHO classification. Histopathology 48:3–12CrossRefPubMedGoogle Scholar
  14. 14.
    Fletcher CD, Dal Cin P, De Wever I et al (1999) Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group. Am J Pathol 154:1841–1847CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Fletcher CDM (2008) Undifferentiated sarcomas: what to do? and does it matter? A surgical pathology Perspective. Ultrastruct Pathol 32:31–36CrossRefPubMedGoogle Scholar
  16. 16.
    Fletcher CDM, Bridge JA, Hogendoorn PC et al (2013) WHO classification of tumours of soft tissue and bone, 4th edn. IARC Press, LyonGoogle Scholar
  17. 17.
    Gladdy RA, Qin LX, Moraco N et al (2010) Do radiation-associated soft tissue sarcomas have the same prognosis as sporadic soft tissue sarcomas? J Clin Oncol Off J Am Soc Clin Oncol 28:2064–2069CrossRefGoogle Scholar
  18. 18.
    Henderson MT, Hollmig ST (2012) Malignant fibrous histiocytoma: changing perceptions and management challenges. J Am Acad Dermatol 67:1335–1341CrossRefPubMedGoogle Scholar
  19. 19.
    Karki B, Xu YK, Wu YK et al (2012) Primary malignant fibrous histiocytoma of the abdominal cavity: CT findings and pathological correlation. World J Radiol 4:151–158CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kransdorf MJ, Murphey MD (2006) Malignant fibrous and fibrohistiocytic tumors. In: Imaging of soft tissue tumors, 2nd edn. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  21. 21.
    Kreiger PA, Judkins AR, Russo PA et al (2009) Loss of INI1 expression defines a unique subset of pediatric undifferentiated soft tissue sarcomas. Modern Pathol Off J US Can Acad Pathol, Inc 22:142–150Google Scholar
  22. 22.
    Laskin WB, Silverman TA, Enzinger FM (1988) Postradiation soft tissue sarcomas. An analysis of 53 cases. Cancer 62:2330–2340CrossRefPubMedGoogle Scholar
  23. 23.
    Lehnhardt M, Daigeler A, Hauser J et al (2008) The value of expert second opinion in diagnosis of soft tissue sarcomas. J Surg Oncol 97:40–43CrossRefPubMedGoogle Scholar
  24. 24.
    Manaster BJ, May DA, Disler DG (2013) Musculoskeletal imaging: the requisites, 4th edn. Saunders, PhiladelphiaGoogle Scholar
  25. 25.
    Mankin HJ, Hornicek FJ, Delaney TF et al (2012) Pleomorphic spindle cell sarcoma (PSCS) formerly known as malignant fibrous histiocytoma (MFH): a complex malignant soft-tissue tumor. Musculoskelet Surg 96:171–177CrossRefPubMedGoogle Scholar
  26. 26.
    Matushansky I, Charytonowicz E, Mills J et al (2009) MFH classification: differentiating undifferentiated pleomorphic sarcoma in the 21st century. Expert Rev Anticancer Ther 9:1135–1144CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Meyers SP (2007) MRI of bone and soft tissue tumors and tumorlike lesions: differential diagnosis and Atlas. Thieme, Stuttgart/New YorkGoogle Scholar
  28. 28.
    Mills AM, Beck AH, Montgomery KD et al (2011) Expression of subtype-specific group 1 leiomyosarcoma markers in a wide variety of sarcomas by gene expression analysis and immunohistochemistry. Am J Surg Pathol 35:583–589CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Mullen JT, Kobayashi W, Wang JJ et al (2012) Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas. Cancer 118:3758–3765CrossRefPubMedGoogle Scholar
  30. 30.
    Murphey MD (2007) World Health Organization classification of bone and soft tissue tumors: modifications and implications for radiologists. Semin Musculoskelet Radiol 11:201–214CrossRefPubMedGoogle Scholar
  31. 31.
    Murphey MD, Gross TM, Rosenthal HG (1994) From the archives of the AFIP. Musculoskeletal malignant fibrous histiocytoma: radiologic-pathologic correlation. Radiogra Rev Publ Radiol Soc N Am, Inc 14:807–826; quiz 827–808Google Scholar
  32. 32.
    Nascimento AF, Raut CP (2008) Diagnosis and management of pleomorphic sarcomas (so-called “MFH”) in adults. J Surg Oncol 97:330–339CrossRefPubMedGoogle Scholar
  33. 33.
    Oda Y, Tamiya S, Oshiro Y et al (2002) Reassessment and clinicopathological prognostic factors of malignant fibrous histiocytoma of soft parts. Pathol Int 52:595–606CrossRefPubMedGoogle Scholar
  34. 34.
    Peiper M, Zurakowski D, Knoefel WT et al (2004) Malignant fibrous histiocytoma of the extremities and trunk: an institutional review. Surgery 135:59–66CrossRefPubMedGoogle Scholar
  35. 35.
    Pierron G, Tirode F, Lucchesi C et al (2012) A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion. Nat Genet 44:461–466CrossRefPubMedGoogle Scholar
  36. 36.
    Reichardt P (2014) Soft tissue sarcomas, a look into the future: different treatments for different subtypes. Future Oncol 10:s19–s27CrossRefPubMedGoogle Scholar
  37. 37.
    Sakharpe A, Lahat G, Gulamhusein T et al (2011) Epithelioid sarcoma and unclassified sarcoma with epithelioid features: clinicopathological variables, molecular markers, and a new experimental model. Oncologist 16:512–522CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Selvarajah S, Yoshimoto M, Prasad M et al (2007) Characterization of trisomy 8 in pediatric undifferentiated sarcomas using advanced molecular cytogenetic techniques. Cancer Genet Cytogenet 174:35–41CrossRefPubMedGoogle Scholar
  39. 39.
    Surace C, Storlazzi CT, Engellau J et al (2005) Molecular cytogenetic characterization of an ins(4;X) occurring as the sole abnormality in an aggressive, poorly differentiated soft tissue sarcoma. Virchows Archiv Int J Pathol 447:869–874CrossRefGoogle Scholar
  40. 40.
    Tateishi U, Hasegawa T, Onaya H et al (2005) Myxoinflammatory fibroblastic sarcoma: MR appearance and pathologic correlation. AJR Am J Roentgenol 184:1749–1753CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • A. Shah
    • 1
  • R. Botchu
    • 1
  • A. M. Davies
    • 1
  • S. L. James
    • 1
    Email author
  1. 1.Royal Orthopaedic Hospital NHS Foundation TrustBirminghamUK

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