Tumors of Uncertain Differentiation

  • Cyril Fisher
Part of the Atlas of Anatomic Pathology book series (AAP)


Tumors of uncertain differentiation include benign and malignant neoplasms with distinctive features but uncertain lineage. Many have consistent genetic aberrations, and this category includes an increasing number of translocation-associated benign soft tissue tumors and sarcomas. Although they sometimes express antigens more characteristic of specific tumor types, such as carcinoma or melanoma, these neoplasms usually do not correspond to any normal cell type and can be regarded as new lineages with characteristic patterns of gene expression. Translocation-associated soft tissue sarcomas, when they have a reciprocal translocation resulting in diploid cells, typically lack nuclear pleomorphism, yet they often are aggressive high-grade sarcomas.


Gastrointestinal Stromal Tumor Synovial Sarcoma Imatinib Mesylate Smooth Muscle Actin Reciprocal Translocation 
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.

Suggested Reading

  1. Allen PW, Dymock RB, MacCormac LB. Superficial angiomyxomas with and without epithelial components. Am J Surg Pathol. 1988;12:519–30.PubMedCrossRefGoogle Scholar
  2. 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;46:1051–60.PubMedCrossRefGoogle Scholar
  3. Antonescu CR, Zhang L, Nielsen GP, Rosenberg AE, Cin PD, Fletcher CD. Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor. Genes Chromosomes Cancer. 2011;50:757–64.PubMedCrossRefGoogle Scholar
  4. Bahrami A, Weiss SW, Montgomery E, Horvai AE, Jin L, Inwards CY, et al. RT-PCR analysis for FGF23 using paraffin sections in the diagnosis of phosphaturic mesenchymal tumors with and without known tumor induced osteomalacia. Am J Surg Pathol. 2009;33:1348–54.PubMedCrossRefGoogle Scholar
  5. Browne TJ, Fletcher CD. Haemosiderotic fibrolipomatous tumour (so-called haemosiderotic fibrohistiocytic lipomatous tumour): analysis of 13 new cases in support of a distinct entity. Histopathology. 2006;48:453–61.PubMedCrossRefGoogle Scholar
  6. Calonje E, Guerin D, McCormick D, Fletcher CD. Superficial angiomyxoma: clinicopathologic analysis of a series of distinctive but poorly recognized cutaneous tumors with tendency for recurrence. Am J Surg Pathol. 1999;23:910–7.PubMedCrossRefGoogle Scholar
  7. Chase DR, Enzinger FM. Epithelioid sarcoma. Diagnosis, prognostic indicators, and treatment. Am J Surg Pathol. 1985;9:241–63.PubMedCrossRefGoogle Scholar
  8. Delaney D, Diss TC, Presneau N, Hing S, Berisha F, Idowu BD, et al. GNAS1 mutations occur more commonly than previously thought in intramuscular myxoma. Mod Pathol. 2009;22:718–24.PubMedCrossRefGoogle Scholar
  9. Enzinger FM. Clear-cell sarcoma of tendons and aponeuroses. An analysis of 21 cases. Cancer. 1965;18:1163–74.PubMedCrossRefGoogle Scholar
  10. Enzinger FM. Epithelioid sarcoma. A sarcoma simulating a granuloma or a carcinoma. Cancer. 1970;26:1029–41.PubMedCrossRefGoogle Scholar
  11. Enzinger FM, Weiss SW, Liang CY. Ossifying fibromyxoid tumor of soft parts. A clinicopathological analysis of 59 cases. Am J Surg Pathol. 1989;13:817–27.PubMedCrossRefGoogle Scholar
  12. Fetsch JF, Laskin WB, Miettinen M. Superficial acral fibromyxoma: a clinicopathologic and immunohistochemical analysis of 37 cases of a distinctive soft tissue tumor with a predilection for the fingers and toes. Hum Pathol. 2001;32:704–14.PubMedCrossRefGoogle Scholar
  13. Fetsch JF, Laskin WB, Michal M, Remotti F, Heffner D, Ellis G, et al. Ectopic hamartomatous thymoma: a clinicopathologic and immunohistochemical analysis of 21 cases with data supporting reclassification as a branchial anlage mixed tumor. Am J Surg Pathol. 2004;28:1360–70.PubMedCrossRefGoogle Scholar
  14. Fisher C. Epithelioid sarcoma of Enzinger. Adv Anat Pathol. 2006;13:114–21.PubMedCrossRefGoogle Scholar
  15. Fisher C, Hedges M, Weiss SW. Ossifying fibromyxoid tumor of soft parts with stromal cyst formation and ribosome-lamella complexes. Ultrastruct Pathol. 1994;18:593–600.PubMedCrossRefGoogle Scholar
  16. Folpe AL, Deyrup AT. Alveolar soft-part sarcoma: a review and update. J Clin Pathol. 2006;59:1127–32.PubMedCrossRefGoogle Scholar
  17. Folpe AL, Weiss SW. Ossifying fibromyxoid tumor of soft parts: a clinicopathologic study of 70 cases with emphasis on atypical and malignant variants. Am J Surg Pathol. 2003;27:421–31.PubMedCrossRefGoogle Scholar
  18. Folpe AL, Weiss SW. Pleomorphic hyalinizing angiectatic tumor: analysis of 41 cases supporting evolution from a distinctive precursor lesion. Am J Surg Pathol. 2004;28:1417–25.PubMedCrossRefGoogle Scholar
  19. Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho JY, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol. 2004;28:1–30.PubMedCrossRefGoogle Scholar
  20. Gerald WL, Miller HK, Battifora H, Miettinen M, Silva EG, Rosai J. Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals. Am J Surg Pathol. 1991;15:499–513.PubMedCrossRefGoogle Scholar
  21. Graham RP, Dry S, Li X, Binder S, Bahrami A, Raimondi SC, et al. Ossifying fibromyxoid tumor of soft parts: a clinicopathologic, proteomic, and genomic study. Am J Surg Pathol. 2011;35:1615–25.PubMedCrossRefGoogle Scholar
  22. Hollmann TJ, Bovee JV, Fletcher CD. Digital fibromyxoma (superficial acral fibromyxoma): a detailed characterization of 124 cases. Am J Surg Pathol. 2012;36:789–98.PubMedCrossRefGoogle Scholar
  23. Kilpatrick SE, Ward WG, Mozes M, Miettinen M, Fukunaga M, Fletcher CD. Atypical and malignant variants of ossifying fibromyxoid tumor. Clinicopathologic analysis of six cases. Am J Surg Pathol. 1995;19:1039–46.PubMedCrossRefGoogle Scholar
  24. Kosemehmetoglu K, Folpe A. Clear cell sarcoma of tendons and aponeuroses, and osteoclast-rich tumour of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: a review and update. J Clin Pathol. 2010;63:416–23.PubMedCrossRefGoogle Scholar
  25. Ladanyi M, Gerald W. Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res. 1994;54:2837–40.PubMedGoogle Scholar
  26. 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;20:48–57.PubMedCrossRefGoogle Scholar
  27. Marshall-Taylor C, Fanburg-Smith JC. Hemosiderotic fibrohistiocytic lipomatous lesion: ten cases of a previously undescribed fatty lesion of the foot/ankle. Mod Pathol. 2000;13:1192–9.PubMedCrossRefGoogle Scholar
  28. Mazabraud A, Semat P, Roze R. [Apropos of the association of fibromyxomas of the soft tissues with fibrous dysplasia of the bones]. Presse Med. 1967;75:2223–8.PubMedGoogle Scholar
  29. Meis JM, Enzinger FM. Juxta-articular myxoma: a clinical and pathological study of 65 cases. Hum Pathol. 1992;23:639–46.PubMedCrossRefGoogle Scholar
  30. Miettinen M. Ossifying fibromyxoid tumor of soft parts. Additional observations of a distinctive soft tissue tumor. Am J Clin Pathol. 1991;95:142–9.PubMedGoogle Scholar
  31. Ordonez NG. Desmoplastic small round cell tumor: I: a histopathologic study of 39 cases with emphasis on unusual histological patterns. Am J Surg Pathol. 1998a;22:1303–13.PubMedCrossRefGoogle Scholar
  32. Ordonez NG. Desmoplastic small round cell tumor: II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers. Am J Surg Pathol. 1998b;22:1314–27.PubMedCrossRefGoogle Scholar
  33. Smith ME, Fisher C, Weiss SW. Pleomorphic hyalinizing angiectatic tumor of soft parts. A low-grade neoplasm resembling neurilemoma. Am J Surg Pathol. 1996;20:21–9.PubMedCrossRefGoogle Scholar
  34. Thway K. Angiomatoid fibrous histiocytoma: a review with recent genetic findings. Arch Pathol Lab Med. 2008;132:273–7.PubMedGoogle Scholar
  35. Zamecnik M, Michal M, Simpson RH, Lamovec J, Hlavcak P, Kinkor Z, et al. Ossifying fibromyxoid tumor of soft parts: a report of 17 cases with emphasis on unusual histological features. Ann Diagn Pathol. 1997;1:73–81.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Cyril Fisher
    • 1
  1. 1.Department of HistopathologyThe Royal Marsden HospitalLondonUK

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