Advertisement

Soft Tissue Special Issue: Cutaneous Pleomorphic Spindle Cell Tumors

  • Thomas BrennEmail author
Special Issue: Soft Tissue

Abstract

This manuscript provides an overview of pleomorphic spindle cell tumors presenting on sun-damaged skin of the elderly and includes discussions of atypical fibroxanthoma, pleomorphic dermal sarcoma, spindle cell and metaplastic squamous cell carcinoma, spindle cell and dedifferentiated melanoma and poorly differentiated cutaneous angiosarcoma. These tumors share many of the clinical presenting and histological features, making confident diagnosis challenging. A reliable and robust diagnosis is necessary to predict behavior as the biologic potential of these tumors ranges from benign (e.g. atypical fibroxanthoma) to outright malignant with poor survival rates (e.g. cutaneous angiosarcoma). The salient clinical, histologic and immunohistochemical characteristics are discussed in detail with emphasis on distinguishing features and differential diagnosis to provide the reader with a better understanding of these entities and helpful clues for a more robust diagnosis.

Keywords

AFX SCC Melanoma Tumor Immunohistochemistry 

Notes

References

  1. 1.
    Brenn T. Pleomorphic dermal neoplasms: a review. Adv Anat Pathol. 2014;21(2):108–30.  https://doi.org/10.1097/PAP.0000000000000009.CrossRefPubMedGoogle Scholar
  2. 2.
    Miller K, Goodlad JR, Brenn T. Pleomorphic dermal sarcoma: adverse histologic features predict aggressive behavior and allow distinction from atypical fibroxanthoma. Am J Surg Pathol. 2012;36(9):1317–26.  https://doi.org/10.1097/PAS.0b013e31825359e1.CrossRefPubMedGoogle Scholar
  3. 3.
    Beer TW, Drury P, Heenan PJ. Atypical fibroxanthoma: a histological and immunohistochemical review of 171 cases. Am J Dermatopathol. 2010;32(6):533–40.  https://doi.org/10.1097/DAD.0b013e3181c80b97.CrossRefPubMedGoogle Scholar
  4. 4.
    Luzar B, Calonje E. Morphological and immunohistochemical characteristics of atypical fibroxanthoma with a special emphasis on potential diagnostic pitfalls: a review. J Cutan Pathol. 2010;37(3):301–9.  https://doi.org/10.1111/j.1600-0560.2009.01425.x.CrossRefPubMedGoogle Scholar
  5. 5.
    Mirza B, Weedon D. Atypical fibroxanthoma: a clinicopathological study of 89 cases. Aust J Dermatol. 2005;46(4):235–8.  https://doi.org/10.1111/j.1440-0960.2005.00190.x.CrossRefGoogle Scholar
  6. 6.
    Mentzel T, Requena L, Brenn T. Atypical fibroxanthoma revisited. Surg Pathol Clin. 2017;10(2):319–35.  https://doi.org/10.1016/j.path.2017.01.007.CrossRefPubMedGoogle Scholar
  7. 7.
    Thum C, Husain EA, Mulholland K, Hornick JL, Brenn T. Atypical fibroxanthoma with pseudoangiomatous features: a histological and immunohistochemical mimic of cutaneous angiosarcoma. Ann Diagn Pathol. 2013;17(6):502–7.  https://doi.org/10.1016/j.anndiagpath.2013.08.004.CrossRefPubMedGoogle Scholar
  8. 8.
    Kanner WA, Brill LB 2nd, Patterson JW, Wick MR. CD10, p63 and CD99 expression in the differential diagnosis of atypical fibroxanthoma, spindle cell squamous cell carcinoma and desmoplastic melanoma. J Cutan Pathol. 2010;37(7):744–50.  https://doi.org/10.1111/j.1600-0560.2010.01534.x.CrossRefPubMedGoogle Scholar
  9. 9.
    Tallon B, Beer TW. MITF positivity in atypical fibroxanthoma: a diagnostic pitfall. Am J Dermatopathol. 2014;36(11):888–91.  https://doi.org/10.1097/DAD.0000000000000054.CrossRefPubMedGoogle Scholar
  10. 10.
    Thum C, Hollowood K, Birch J, Goodlad JR, Brenn T. Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin. J Cutan Pathol. 2011;38(12):954–60.  https://doi.org/10.1111/j.1600-0560.2011.01798.x.CrossRefPubMedGoogle Scholar
  11. 11.
    Griewank KG, Schilling B, Murali R, Bielefeld N, Schwamborn M, Sucker A, et al. TERT promoter mutations are frequent in atypical fibroxanthomas and pleomorphic dermal sarcomas. Mod Pathol. 2014;27(4):502–8.  https://doi.org/10.1038/modpathol.2013.168.CrossRefPubMedGoogle Scholar
  12. 12.
    Griewank KG, Wiesner T, Murali R, Pischler C, Muller H, Koelsche C, et al. Atypical fibroxanthoma and pleomorphic dermal sarcoma harbor frequent NOTCH1/2 and FAT1 mutations and similar DNA copy number alteration profiles. Mod Pathol. 2018;31(3):418–28.  https://doi.org/10.1038/modpathol.2017.146.CrossRefPubMedGoogle Scholar
  13. 13.
    Koelsche C, Stichel D, Griewank KG, Schrimpf D, Reuss DE, Bewerunge-Hudler M, et al. Genome-wide methylation profiling and copy number analysis in atypical fibroxanthomas and pleomorphic dermal sarcomas indicate a similar molecular phenotype. Clin Sarcoma Res. 2019;9:2.  https://doi.org/10.1186/s13569-019-0113-6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wollina U, Schonlebe J, Ziemer M, Friedling F, Koch A, Haroske G, et al. Atypical fibroxanthoma: a series of 56 tumors and an unexplained uneven distribution of cases in southeast Germany. Head Neck. 2015;37(6):829–34.  https://doi.org/10.1002/hed.23673.CrossRefPubMedGoogle Scholar
  15. 15.
    Tardio JC, Pinedo F, Aramburu JA, Suarez-Massa D, Pampin A, Requena L, et al. Pleomorphic dermal sarcoma: a more aggressive neoplasm than previously estimated. J Cutan Pathol. 2016;43(2):101–12.  https://doi.org/10.1111/cup.12603.CrossRefPubMedGoogle Scholar
  16. 16.
    Wang WL, Torres-Cabala C, Curry JL, Ivan D, McLemore M, Tetzlaff M, et al. Metastatic atypical fibroxanthoma: a series of 11 cases including with minimal and no subcutaneous involvement. Am J Dermatopathol. 2015;37(6):455–61.  https://doi.org/10.1097/DAD.0000000000000237.CrossRefPubMedGoogle Scholar
  17. 17.
    Breuninger H, Schaumburg-Lever G, Holzschuh J, Horny HP. Desmoplastic squamous cell carcinoma of skin and vermilion surface: a highly malignant subtype of skin cancer. Cancer. 1997;79(5):915–9.CrossRefGoogle Scholar
  18. 18.
    Velazquez EF, Werchniack AE, Granter SR. Desmoplastic/spindle cell squamous cell carcinoma of the skin. A diagnostically challenging tumor mimicking a scar: clinicopathologic and immunohistochemical study of 6 cases. Am J Dermatopathol. 2010;32(4):333–9.CrossRefGoogle Scholar
  19. 19.
    Sigel JE, Skacel M, Bergfeld WF, House NS, Rabkin MS, Goldblum JR. The utility of cytokeratin 5/6 in the recognition of cutaneous spindle cell squamous cell carcinoma. J Cutan Pathol. 2001;28(10):520–4.CrossRefGoogle Scholar
  20. 20.
    Dotto JE, Glusac EJ. p63 is a useful marker for cutaneous spindle cell squamous cell carcinoma. J Cutan Pathol. 2006;33(6):413–7.  https://doi.org/10.1111/j.0303-6987.2006.00477.x.CrossRefPubMedGoogle Scholar
  21. 21.
    Henderson SA, Torres-Cabala CA, Curry JL, Bassett RL, Ivan D, Prieto VG, et al. p40 is more specific than p63 for the distinction of atypical fibroxanthoma from other cutaneous spindle cell malignancies. Am J Surg Pathol. 2014;38(8):1102–10.  https://doi.org/10.1097/PAS.0000000000000245.CrossRefPubMedGoogle Scholar
  22. 22.
    Tran TA, Muller S, Chaudahri PJ, Carlson JA. Cutaneous carcinosarcoma: adnexal vs. epidermal types define high- and low-risk tumors. Results of a meta-analysis. J Cutan Pathol. 2005;32(1):2–11.  https://doi.org/10.1111/j.0303-6987.2005.00260.x.CrossRefPubMedGoogle Scholar
  23. 23.
    Clark JJ, Bowen AR, Bowen GM, Hyngstrom JR, Hadley ML, Duffy K, et al. Cutaneous carcinosarcoma: a series of six cases and a review of the literature. J Cutan Pathol. 2017;44(1):34–44.  https://doi.org/10.1111/cup.12843.CrossRefPubMedGoogle Scholar
  24. 24.
    Martin B, Poblet E, Rios JJ, Kazakov D, Kutzner H, Brenn T, et al. Merkel cell carcinoma with divergent differentiation: histopathological and immunohistochemical study of 15 cases with PCR analysis for Merkel cell polyomavirus. Histopathology. 2013;62(5):711–22.  https://doi.org/10.1111/his.12091.CrossRefPubMedGoogle Scholar
  25. 25.
    Erstine EM, Tetzlaff MT, Ko JS, Prieto VG, Cheah AL, Billings SD. Living on the edge: diagnosing sarcomatoid melanoma using histopathologic cues at the edge of a dedifferentiated tumor: a report of 2 cases and review of the literature. Am J Dermatopathol. 2017;39(8):593–8.  https://doi.org/10.1097/DAD.0000000000000716.CrossRefPubMedGoogle Scholar
  26. 26.
    Kiuru M, McDermott G, Berger M, Halpern AC, Busam KJ. Desmoplastic melanoma with sarcomatoid dedifferentiation. Am J Surg Pathol. 2014;38(6):864–70.  https://doi.org/10.1097/PAS.0000000000000201.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Banerjee SS, Eyden B. Divergent differentiation in malignant melanomas: a review. Histopathology. 2008;52(2):119–29.  https://doi.org/10.1111/j.1365-2559.2007.02823.x.CrossRefPubMedGoogle Scholar
  28. 28.
    Gharpuray-Pandit D, Coyne J, Eyden B, Banerjee SS. Rhabdomyoblastic differentiation in malignant melanoma in adults: report of 2 cases. Int J Surg Pathol. 2007;15(1):20–5.  https://doi.org/10.1177/1066896906295775.CrossRefPubMedGoogle Scholar
  29. 29.
    Laskin WB, Knittel DR, Frame JN. S100 protein and HMB-45 negative "rhabdoid" malignant melanoma: a totally dedifferentiated malignant melanoma? Am J Clin Pathol. 1995;103(6):772–3.  https://doi.org/10.1093/ajcp/103.6.772.CrossRefPubMedGoogle Scholar
  30. 30.
    Wilsher MJ. Collision tumour: atypical fibroxanthoma and invasive melanoma. Pathology. 2009;41(7):699–701.  https://doi.org/10.3109/00313020903305746.CrossRefPubMedGoogle Scholar
  31. 31.
    Brenn T, Fletcher CD. Postradiation vascular proliferations: an increasing problem. Histopathology. 2006;48(1):106–14.  https://doi.org/10.1111/j.1365-2559.2005.02293.x.CrossRefPubMedGoogle Scholar
  32. 32.
    Morgan MB, Swann M, Somach S, Eng W, Smoller B. Cutaneous angiosarcoma: a case series with prognostic correlation. J Am Acad Dermatol. 2004;50(6):867–74.  https://doi.org/10.1016/j.jaad.2003.10.671.CrossRefPubMedGoogle Scholar
  33. 33.
    Deyrup AT, McKenney JK, Tighiouart M, Folpe AL, Weiss SW. Sporadic cutaneous angiosarcomas: a proposal for risk stratification based on 69 cases. Am J Surg Pathol. 2008;32(1):72–7.  https://doi.org/10.1097/PAS.0b013e3180f633a3.CrossRefPubMedGoogle Scholar
  34. 34.
    McKay KM, Doyle LA, Lazar AJ, Hornick JL. Expression of ERG, an Ets family transcription factor, distinguishes cutaneous angiosarcoma from histological mimics. Histopathology. 2012;61(5):989–91.  https://doi.org/10.1111/j.1365-2559.2012.04286.x.CrossRefPubMedGoogle Scholar
  35. 35.
    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(2):234–42.  https://doi.org/10.1111/j.1600-0560.2011.01843.x.CrossRefPubMedGoogle Scholar
  36. 36.
    Guo T, Zhang L, Chang NE, Singer S, Maki RG, Antonescu CR. Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions. Genes Chromosomes Cancer. 2011;50(1):25–33.  https://doi.org/10.1002/gcc.20827.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ko JS, Billings SD, Lanigan CP, Buehler D, Fernandez AP, Tubbs RR. Fully automated dual-color dual-hapten silver in situ hybridization staining for MYC amplification: a diagnostic tool for discriminating secondary angiosarcoma. J Cutan Pathol. 2014;41(3):286–92.  https://doi.org/10.1111/cup.12278.CrossRefPubMedGoogle Scholar
  38. 38.
    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(1):75–85.  https://doi.org/10.1038/modpathol.2011.134.CrossRefPubMedGoogle Scholar
  39. 39.
    Shon W, Sukov WR, Jenkins SM, Folpe AL. MYC amplification and overexpression in primary cutaneous angiosarcoma: a fluorescence in-situ hybridization and immunohistochemical study. Mod Pathol. 2014;27(4):509–15.  https://doi.org/10.1038/modpathol.2013.163.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Departments of Pathology & Laboratory Medicine and Medicine, The Arnie Charbonneau Cancer Institute, Cumming School of MedicineUniversity of CalgaryCalgaryCanada

Personalised recommendations