Skip to main content

Molecular Testing in Cutaneous Mesenchymal Tumors

  • Chapter
  • First Online:
Book cover Precision Molecular Pathology of Dermatologic Diseases

Part of the book series: Molecular Pathology Library ((MPLB,volume 9))

  • 729 Accesses

Abstract

Mesenchymal tumors can be difficult to diagnose, with those manifesting in the skin presenting unique challenges. Part of the difficultly comes from the rarity of these tumors, in comparison to epithelial and melanocytic tumors. In addition, there are over 50 subtypes of mesenchymal tumors, each with a range of appearances that can histologically overlap with each other, including some benign and malignant entities.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fletcher CDM. World health organization. International agency for research on cancer. WHO classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013.

    Google Scholar 

  2. Wang WL, Bones-Valentin RA, Prieto VG, Pollock RE, Lev DC, Lazar AJ. Sarcoma metastases to the skin: a clinicopathologic study of 65 patients. Cancer. 2012;118:2900–4.

    Article  PubMed  Google Scholar 

  3. Shingde MV, Buckland M, Busam KJ, McCarthy SW, Wilmott J, Thompson JF, et al. Primary cutaneous Ewing sarcoma/primitive neuroectodermal tumour: a clinicopathological analysis of seven cases highlighting diagnostic pitfalls and the role of FISH testing in diagnosis. J Clin Pathol. 2009;62:915–9.

    Article  CAS  PubMed  Google Scholar 

  4. Hantschke M, Mentzel T, Rutten A, Palmedo G, Calonje E, Lazar AJ, et al. Cutaneous clear cell sarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma. Am J Surg Pathol. 2010;34:216–22.

    Article  PubMed  Google Scholar 

  5. Demicco EG, Lazar AJ. Clinicopathologic considerations: how can we fine tune our approach to sarcoma? Semin Oncol. 2011;38(Suppl 3):S3–S18.

    Article  PubMed  Google Scholar 

  6. Lazar AJ, Trent JC, Lev D. Sarcoma molecular testing: diagnosis and prognosis. Curr Oncol Rep. 2007;9:309–15.

    Article  CAS  PubMed  Google Scholar 

  7. Lessnick SL, Dei Tos AP, Sorensen PH, Dileo P, Baker LH, Ferrari S, et al. Small round cell sarcomas. Semin Oncol. 2009;36:338–46.

    Article  CAS  PubMed  Google Scholar 

  8. Hollmann TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol. 2011;35:e47–e63.

    Article  PubMed  Google Scholar 

  9. Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol. 2009;33:542–50.

    Article  PubMed  Google Scholar 

  10. Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw. 2010;8(Suppl 2):S1–41; quiz S2–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Yang J, Du X, Lazar AJ, Pollock R, Hunt K, Chen K, et al. Genetic aberrations of gastrointestinal stromal tumors. Cancer. 2008;113:1532–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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;173:1518–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Weaver J, Downs-Kelly E, Goldblum JR, Turner S, Kulkarni S, Tubbs RR, et al. Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol. 2008;21:943–9.

    Article  CAS  PubMed  Google Scholar 

  14. Boland JM, Folpe AL. Cutaneous neoplasms showing EWSR1 rearrangement. Adv Anat Pathol. 2013;20:75–85.

    Article  CAS  PubMed  Google Scholar 

  15. Fisher C. The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review. Histopathology. 2014;64:134–50.

    Article  PubMed  Google Scholar 

  16. Rossi S, Szuhai K, Ijszenga M, Tanke HJ, Zanatta L, Sciot R, et al. EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. Clin Cancer Res. 2007;13:7322–8.

    Article  CAS  PubMed  Google Scholar 

  17. Thway K, Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol. 2012;36:e1–e11.

    Article  PubMed  Google Scholar 

  18. Wang WL, Mayordomo E, Zhang W, Hernandez VS, Tuvin D, Garcia L, et al. Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol. 2009;22:1201–9.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma–association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006;12:5356–62.

    Article  CAS  PubMed  Google Scholar 

  21. Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosom Cancer. 2011;50:559–70.

    Article  CAS  PubMed  Google Scholar 

  22. Yancoskie AE, Sreekantaiah C, Jacob J, Rosenberg A, Edelman M, Antonescu CR, et al. EWSR1 and ATF1 rearrangements in clear cell odontogenic carcinoma: presentation of a case. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;118:e115–8.

    Article  PubMed  Google Scholar 

  23. Thway K, Nicholson AG, Lawson K, Gonzalez D, Rice A, Balzer B, et al. Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity. Am J Surg Pathol. 2011;35:1722–32.

    Article  PubMed  Google Scholar 

  24. Bilodeau EA, Weinreb I, Antonescu CR, Zhang L, Dacic S, Muller S, et al. Clear cell odontogenic carcinomas show EWSR1 rearrangements: a novel finding and a biological link to salivary clear cell carcinomas. Am J Surg Pathol. 2013;37:1001–5.

    Article  PubMed  Google Scholar 

  25. Mejia-Guerrero S, Quejada M, Gokgoz N, Gill M, Parkes RK, Wunder JS, et al. Characterization of the 12q15 MDM2 and 12q13-14 CDK4 amplicons and clinical correlations in osteosarcoma. Genes Chromosom Cancer. 2010;49:518–25.

    CAS  PubMed  Google Scholar 

  26. Patel KU, Szabo SS, Hernandez VS, Prieto VG, Abruzzo LV, Lazar AJ, et al. Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays. Hum Pathol. 2008;39:184–93.

    Article  CAS  PubMed  Google Scholar 

  27. Antonescu CR, Tschernyavsky SJ, Woodruff JM, Jungbluth AA, Brennan MF, Ladanyi M. Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. J Mol Diagn. 2002;4:44–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mentzel T, Scharer L, Kazakov DV, Michal M. Myxoid dermatofibrosarcoma protuberans: clinicopathologic, immunohistochemical, and molecular analysis of eight cases. Am J Dermatopathol. 2007;29:443–8.

    Article  PubMed  Google Scholar 

  29. Zelger BW, Ofner D, Zelger BG. Atrophic variants of dermatofibroma and dermatofibrosarcoma protuberans. Histopathology. 1995;26:519–27.

    Article  CAS  PubMed  Google Scholar 

  30. Mentzel T, Beham A, Katenkamp D, Dei Tos AP, Fletcher CD. Fibrosarcomatous (“high-grade”) dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol. 1998;22:576–87.

    Article  CAS  PubMed  Google Scholar 

  31. Swaby MG, Evans HL, Fletcher CD, Prieto VG, Patel KU, Lev DC, et al. Dermatofibrosarcoma protuberans with unusual sarcomatous transformation: a series of 4 cases with molecular confirmation. Am J Dermatopathol. 2011;33:354–60.

    Article  PubMed  Google Scholar 

  32. Wang WL, Patel KU, Coleman NM, Smith-Zagone MJ, Ivan D, Reed JA, et al. COL1A1:PDGFB chimeric transcripts are not present in indeterminate fibrohistiocytic lesions of the skin. Am J Dermatopathol. 2010;32:149–53.

    Article  PubMed  Google Scholar 

  33. Kutzner H, Mentzel T, Palmedo G, Hantschke M, Rutten A, Paredes BE, et al. Plaque-like CD34-positive dermal fibroma (“medallion-like dermal dendrocyte hamartoma”): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans. Am J Surg Pathol. 2010;34:190–201.

    Article  PubMed  Google Scholar 

  34. Weaver J, Billings SD. Postradiation cutaneous vascular tumors of the breast: a review. Semin Diagn Pathol. 2009;26:141–9.

    Article  PubMed  Google Scholar 

  35. Flucke U, Requena L, Mentzel T. Radiation-induced vascular lesions of the skin: an overview. Adv Anat Pathol. 2013;20:407–15.

    Article  CAS  PubMed  Google Scholar 

  36. Fernandez AP, Sun Y, Tubbs RR, Goldblum JR, Billings SD. FISH for MYC amplification and anti-MYC immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular proliferations. J Cutan Pathol. 2012;39:234–42.

    Article  PubMed  Google Scholar 

  37. Mentzel T, Schildhaus HU, Palmedo G, Buttner R, Kutzner H. Postradiation cutaneous angiosarcoma after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and control cases: clinicopathological, immunohistochemical and molecular analysis of 66 cases. Mod Pathol. 2012;25:75–85.

    Article  CAS  PubMed  Google Scholar 

  38. Billings SD, Folpe AL, Weiss SW. Epithelioid Sarcoma-like hemangioendothelioma (pseudomyogenic hemangioendothelioma). Am J Surg Pathol. 2011;35:1088; author reply—9.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  40. 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;232:534–40.

    Article  CAS  PubMed  Google Scholar 

  41. Antonescu CR, Zhang L, Chang NE, Pawel BR, Travis W, Katabi N, et al. EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosom Cancer. 2010;49:1114–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Agaram NP, Chen HW, Zhang L, Sung YS, Panicek D, Healey JH, et al. EWSR1-PBX3: a novel gene fusion in myoepithelial tumors. Genes Chromosom Cancer. 2015;54:63–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Huang SC, Chen HW, Zhang L, Sung YS, Agaram NP, Davis M, et al. Novel FUS-KLF17 and EWSR1-KLF17 fusions in myoepithelial tumors. Genes Chromosom Cancer. 2015;54(5):267–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Antonescu CR, Zhang L, Shao SY, Mosquera JM, Weinreb I, Katabi N, et al. Frequent PLAG1 gene rearrangements in skin and soft tissue myoepithelioma with ductal differentiation. Genes Chromosom Cancer. 2013;52:675–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang WL, Mayordomo E, Czerniak BA, Abruzzo LV, Dal Cin P, Araujo DM, et al. Fluorescence in situ hybridization is a useful ancillary diagnostic tool for extraskeletal myxoid chondrosarcoma. Mod Pathol. 2008;21:1303–10.

    Article  CAS  PubMed  Google Scholar 

  46. Paredes BE, Mentzel T. Atypical lipomatous tumor/“well-differentiated liposarcoma” of the skin clinically presenting as a skin tag: clinicopathologic, immunohistochemical, and molecular analysis of 2 cases. Am J Dermatopathol. 2011;33:603–7.

    Article  PubMed  Google Scholar 

  47. Al-Zaid T, Wang WL, Lopez-Terrada D, Lev D, Hornick JL, Hafeez Diwan A, et al. Pleomorphic fibroma and dermal atypical lipomatous tumor: are they related? J Cutan Pathol. 2013;40:379–84.

    Article  PubMed  Google Scholar 

  48. Dei Tos AP, Mentzel T, Fletcher CD. Primary liposarcoma of the skin: a rare neoplasm with unusual high grade features. Am J Dermatopathol. 1998;20:332–8.

    Article  CAS  PubMed  Google Scholar 

  49. Sachdeva MP, Goldblum JR, Rubin BP, Billings SD. Low-fat and fat-free pleomorphic lipomas: a diagnostic challenge. Am J Dermatopathol. 2009;31:423–6.

    Article  PubMed  Google Scholar 

  50. Gardner JM, Dandekar M, Thomas D, Goldblum JR, Weiss SW, Billings SD, et al. Cutaneous and subcutaneous pleomorphic liposarcoma: a clinicopathologic study of 29 cases with evaluation of MDM2 gene amplification in 26. Am J Surg Pathol. 2012;36:1047–51.

    Article  PubMed  Google Scholar 

  51. Tanas MR, Rubin BP, Tubbs RR, Billings SD, Downs-Kelly E, Goldblum JR. Utilization of fluorescence in situ hybridization in the diagnosis of 230 mesenchymal neoplasms: an institutional experience. Arch Pathol Lab Med. 2010;134:1797–803.

    PubMed  Google Scholar 

  52. Marburger TB, Gardner JM, Prieto VG, Billings SD. Primary cutaneous rhabdomyosarcoma: a clinicopathologic review of 11 cases. J Cutan Pathol. 2012;39:987–95.

    Article  PubMed  Google Scholar 

  53. Fletcher CD, McKee PH. Sarcomas–a clinicopathological guide with particular reference to cutaneous manifestation. III. Angiosarcoma, malignant haemangiopericytoma, fibrosarcoma and synovial sarcoma. Clin Exp Dermatol. 1985;10:332–49.

    Article  CAS  PubMed  Google Scholar 

  54. Ehrig T, Billings SD, Fanburg-Smith JC. Superficial primitive neuroectodermal tumor/Ewing sarcoma (PN/ES): same tumor as deep PN/ES or new entity? Ann Diagn Pathol. 2007;11:153–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wei-Lien Wang MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wang, WL., Lazar, A. (2015). Molecular Testing in Cutaneous Mesenchymal Tumors. In: Prieto, V. (eds) Precision Molecular Pathology of Dermatologic Diseases. Molecular Pathology Library, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2861-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2861-3_3

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-2860-6

  • Online ISBN: 978-1-4939-2861-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics