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Immunohistology and Molecular Studies of Fibrohistiocytic and Myofibroblastic Cutaneous Tumors

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Applied Immunohistochemistry in the Evaluation of Skin Neoplasms

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Abstract

Fibrohistiocytic tumors of the skin and superficial soft tissues represent an increasingly obsolete rubric. Lesions in this category are defined largely based on morphology, and in reality represent mesenchymal lesions with variable fibroblastic and myofibroblastic differentiation. As such, we restricted our review to the following entities: dermatofibroma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, plaque-like CD34-positive dermal fibroma, plexiform fibrohistiocytic tumor, and myxoinflammatory fibroblastic sarcoma. The pertinent immunohistochemical and molecular features of each entity are described, together with common pitfalls and differential diagnosis clues.

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References

  1. Gru AA, Santa Cruz DJ. Atypical fibroxanthoma: a selective review. Semin Diagn Pathol. 2013;30(1):4–12.

    Article  PubMed  Google Scholar 

  2. Luzar B, Calonje E. Cutaneous fibrohistiocytic tumours – an update. Histopathology. 2010;56(1):148–65.

    Article  PubMed  Google Scholar 

  3. Fletcher CDM, World HH. WHO classification of tumours of soft tissue and bone. Lyon: IARC Press; 2013.

    Google Scholar 

  4. Szablewski V, Laurent-Roussel S, Rethers L, Rommel A, Van Eeckhout P, Vaneechout P, et al. Atypical fibrous histiocytoma of the skin with CD30 and p80/ALK1 positivity and ALK gene rearrangement. J Cutan Pathol. 2014;41(9):715–9.

    Article  PubMed  Google Scholar 

  5. Doyle LA, Mariño-Enriquez A, Fletcher CD, Hornick JL. ALK rearrangement and overexpression in epithelioid fibrous histiocytoma. Mod Pathol. 2015;28(7):904–12.

    Article  CAS  PubMed  Google Scholar 

  6. Kim HJ, Lee JY, Kim SH, Seo YJ, Lee JH, Park JK, et al. Stromelysin-3 expression in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans: comparison with factor XIIIa and CD34. Br J Dermatol. 2007;157(2):319–24.

    Article  CAS  PubMed  Google Scholar 

  7. Bandarchi B, Ma L, Marginean C, Hafezi S, Zubovits J, Rasty G. D2-40, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans. Mod Pathol. 2010;23(3):434–8.

    Article  CAS  PubMed  Google Scholar 

  8. West RB, Harvell J, Linn SC, Liu CL, Prapong W, Hernandez-Boussard T, et al. Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans. Am J Surg Pathol. 2004;28(8):1063–9.

    Article  PubMed  Google Scholar 

  9. Horenstein MG, Prieto VG, Nuckols JD, Burchette JL, Shea CR. Indeterminate fibrohistiocytic lesions of the skin: is there a spectrum between dermatofibroma and dermatofibrosarcoma protuberans? Am J Surg Pathol. 2000;24(7):996–1003.

    Article  CAS  PubMed  Google Scholar 

  10. Goldblum JR, Folpe AL, Weiss SW, Enzinger FMSTT, Weiss SWEASTT. Enzinger and Weiss’s soft tissue tumors. Philadelphia, PA: Saunders/Elsevier; 2014.

    Google Scholar 

  11. Palmerini E, Gambarotti M, Staals EL, Zanella L, Sieberova G, Longhi A, et al. Fibrosarcomatous changes and expression of CD34+ and apolipoprotein-D in dermatofibrosarcoma protuberans. Clin Sarcoma Res. 2012;2(1):4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pedeutour F, Simon MP, Minoletti F, Barcelo G, Terrier-Lacombe MJ, Combemale P, et al. Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor-associated chromosome rearrangement. Cytogenet Cell Genet. 1996;72(2–3):171–4.

    Article  CAS  PubMed  Google Scholar 

  13. Simon MP, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet. 1997;15(1):95–8.

    Article  CAS  PubMed  Google Scholar 

  14. O’Brien KP, Seroussi E, Dal Cin P, Sciot R, Mandahl N, Fletcher JA, et al. Various regions within the alpha-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomas. Genes Chromosomes Cancer. 1998;23(2):187–93.

    Article  PubMed  Google Scholar 

  15. Sirvent N, Maire G, Pedeutour F. Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer. 2003;37(1):1–19.

    Article  CAS  PubMed  Google Scholar 

  16. Wang J, Hisaoka M, Shimajiri S, Morimitsu Y, Hashimoto H. Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues. Diagn Mol Pathol. 1999;8(3):113–9.

    Article  CAS  PubMed  Google Scholar 

  17. Salgado R, Llombart B, Pujol RM, Fernández-Serra A, Sanmartín O, Toll A, et al. Molecular diagnosis of dermatofibrosarcoma protuberans: a comparison between reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization methodologies. Genes Chromosomes Cancer. 2011;50(7):510–7.

    Article  CAS  PubMed  Google Scholar 

  18. Karanian M, Pérot G, Coindre JM, Chibon F, Pedeutour F, Neuville A. Fluorescence in situ hybridization analysis is a helpful test for the diagnosis of dermatofibrosarcoma protuberans. Mod Pathol. 2015;28(2):230–7.

    Article  CAS  PubMed  Google Scholar 

  19. Patel KU, Szabo SS, Hernandez VS, Prieto VG, Abruzzo LV, Lazar AJ, López-Terrada D. 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(2):184–93.

    Article  CAS  PubMed  Google Scholar 

  20. Bianchini L, Maire G, Guillot B, Joujoux JM, Follana P, Simon MP, et al. Complex t(5;8) involving the CSPG2 and PTK2B genes in a case of dermatofibrosarcoma protuberans without the COL1A1-PDGFB fusion. Virchows Arch. 2008;452(6):689–96.

    Article  CAS  PubMed  Google Scholar 

  21. Syed S, Martin AM, Haupt H, Podolski V, Brooks JJ. Frequent detection of androgen receptors in spindle cell lipomas. Arch Pathol Lab Med. 2008;132:81–3.

    PubMed  Google Scholar 

  22. Kutzner H, Mentzel T, Palmedo G, Hantschke M, Rütten 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(2):190–201.

    Article  PubMed  Google Scholar 

  23. Mirza B, Weedon D. Atypical fibroxanthoma: a clinicopathological study of 89 cases. Australas J Dermatol. 2005;46(4):235–8.

    Article  PubMed  Google Scholar 

  24. Brenn T. Pleomorphic dermal neoplasms: a review. Adv Anat Pathol. 2014;21(2):108–30.

    Article  PubMed  Google Scholar 

  25. 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.

    Article  PubMed  Google Scholar 

  26. Nonaka D, Bishop PW. Sarcoma-like tumor of head and neck skin. Am J Surg Pathol. 2014;38(7):956–65.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  PubMed  Google Scholar 

  28. Kanner WA, Brill LB, 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.

    Article  PubMed  Google Scholar 

  29. Alomari AK, Glusac EJ, McNiff JM. P40 is a more specific marker than p63 for cutaneous poorly differentiated squamous cell carcinoma. J Cutan Pathol. 2014;41(11):839–45.

    Article  PubMed  Google Scholar 

  30. Henderson SA, Torres-Cabala CA, Curry JL, Bassett RL, Ivan D, Prieto VG, Tetzlaff MT. 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.

    PubMed  Google Scholar 

  31. Cuda J, Mirzamani N, Kantipudi R, Robbins J, Welsch MJ, Sundram UN. Diagnostic utility of fli-1 and D2-40 in distinguishing atypical fibroxanthoma from angiosarcoma. Am J Dermatopathol. 2013;35(3):316–8.

    Article  PubMed  Google Scholar 

  32. Bull C, Mirzabeigi M, Laskin W, Dubina M, Traczyc T, Guitart J, Gerami P. Diagnostic utility of low-affinity nerve growth factor receptor (P 75) immunostaining in atypical fibroxanthoma. J Cutan Pathol. 2011;38(8):631–5.

    Article  PubMed  Google Scholar 

  33. Wieland CN, Dyck R, Weenig RH, Comfere NI. The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma. J Cutan Pathol. 2011;38(11):884–8.

    Article  PubMed  Google Scholar 

  34. Monteagudo C, Calduch L, Navarro S, Joan-Figueroa A, Llombart-Bosch A. CD99 immunoreactivity in atypical fibroxanthoma: a common feature of diagnostic value. Am J Clin Pathol. 2002;117(1):126–31.

    Article  PubMed  Google Scholar 

  35. Rodríguez-Jurado R, Palacios C, Durán-McKinster C, Mercadillo P, Orozco-Covarrubias L, Saez-de-Ocariz Mdel M, Ruiz-Maldonado R. Medallion-like dermal dendrocyte hamartoma: a new clinically and histopathologically distinct lesion. J Am Acad Dermatol. 2004;51(3):359–63.

    Article  PubMed  Google Scholar 

  36. Shah KN, Anderson E, Junkins-Hopkins J, James WD. Medallion-like dermal dendrocyte hamartoma. Pediatr Dermatol. 2007;24(6):632–6.

    Article  PubMed  Google Scholar 

  37. Marque M, Bessis D, Pedeutour F, Viseux V, Guillot B, Fraitag-Spinner S. Medallion-like dermal dendrocyte hamartoma: the main diagnostic pitfall is congenital atrophic dermatofibrosarcoma. Br J Dermatol. 2009;160(1):190–3.

    Article  CAS  PubMed  Google Scholar 

  38. Hollowood K, Holley MP, Fletcher CD. Plexiform fibrohistiocytic tumour: clinicopathological, immunohistochemical and ultrastructural analysis in favour of a myofibroblastic lesion. Histopathology. 1991;19(6):503–13.

    Article  CAS  PubMed  Google Scholar 

  39. Enzinger FM, Zhang RY. Plexiform fibrohistiocytic tumor presenting in children and young adults: an analysis of 65 cases. Am J Surg Pathol. 1988;12(11):818–26.

    Article  CAS  PubMed  Google Scholar 

  40. Remstein ED, Arndt CA, Nascimento AG. Plexiform fibrohistiocytic tumor: clinicopathologic analysis of 22 cases. Am J Surg Pathol. 1999;23(6):662–70.

    Article  CAS  PubMed  Google Scholar 

  41. Muezzinoglu B, Tohumcu A, Ekingen G. An unusual occurrence of plexiform fibrohistiocytic tumour: congenital tumour diagnosed at 7 years of age. Pathology. 2011;43(4):380–1.

    Article  PubMed  Google Scholar 

  42. Moosavi C, Jha P, Fanburg-Smith JC. An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the armed forces institute of pathology, in honor of Franz M. Enzinger, MD. Ann Diagn Pathol. 2007;11(5):313–9.

    Article  PubMed  Google Scholar 

  43. Smith S, Fletcher CD, Smith MA, Gusterson BA. Cytogenetic analysis of a plexiform fibrohistiocytic tumor. Cancer Genet Cytogenet. 1990;48(1):31–4.

    Article  CAS  PubMed  Google Scholar 

  44. Redlich GC, Montgomery KD, Allgood GA, Joste NE. Plexiform fibrohistiocytic tumor with a clonal cytogenetic anomaly. Cancer Genet Cytogenet. 1999;108(2):141–3.

    Article  CAS  PubMed  Google Scholar 

  45. Leclerc-Mercier S, Pedeutour F, Fabas T, Glorion C, Brousse N, Fraitag S. Plexiform fibrohistiocytic tumor with molecular and cytogenetic analysis. Pediatr Dermatol. 2011;28(1):26–9.

    Article  PubMed  Google Scholar 

  46. Jaffer S, Ambrosini-Spaltro A, Mancini AM, Eusebi V, Rosai J. Neurothekeoma and plexiform fibrohistiocytic tumor: mere histologic resemblance or histogenetic relationship? Am J Surg Pathol. 2009;33(6):905–13.

    Article  PubMed  Google Scholar 

  47. Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P, et al. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 2013;45(12):1479–82.

    Article  CAS  PubMed  Google Scholar 

  48. Fox MD, Billings SD, Gleason BC, Moore J, Thomas AB, Shea CR, et al. Expression of MiTF may be helpful in differentiating cellular neurothekeoma from plexiform fibrohistiocytic tumor (histiocytoid predominant) in a partial biopsy specimen. Am J Dermatopathol. 2012;34(2):157–60.

    Article  PubMed  Google Scholar 

  49. Seethala RR, Goldblum JR, Hicks DG, Lehman M, Khurana JS, Pasha TL, Zhang PJ. Immunohistochemical evaluation of microphthalmia-associated transcription factor expression in giant cell lesions. Mod Pathol. 2004;17(12):1491–6.

    Article  PubMed  Google Scholar 

  50. Meis-Kindblom JM, Kindblom LG. Acral myxoinflammatory fibroblastic sarcoma: a low-grade tumor of the hands and feet. Am J Surg Pathol. 1998;22(8):911–24.

    Article  CAS  PubMed  Google Scholar 

  51. Montgomery EA, Devaney KO, Giordano TJ, Weiss SW. Inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternberg-like cells: a distinctive lesion with features simulating inflammatory conditions, Hodgkin’s disease, and various sarcomas. Mod Pathol. 1998;11(4):384–91.

    CAS  PubMed  Google Scholar 

  52. Michal M. Inflammatory myxoid tumor of the soft parts with bizarre giant cells. Pathol Res Pract. 1998;194(8):529–33.

    Article  CAS  PubMed  Google Scholar 

  53. Laskin WB, Fetsch JF, Miettinen M. Myxoinflammatory fibroblastic sarcoma: a clinicopathologic analysis of 104 cases, with emphasis on predictors of outcome. Am J Surg Pathol. 2014;38(1):1–12.

    Article  PubMed  Google Scholar 

  54. Lombardi R, Jovine E, Zanini N, Salone MC, Gambarotti M, Righi A, et al. A case of lung metastasis in myxoinflammatory fibroblastic sarcoma: analytical review of one hundred and thirty eight cases. Int Orthop. 2013;37(12):2429–36.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Hallor KH, Sciot R, Staaf J, Heidenblad M, Rydholm A, Bauer HC, et al. Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions. J Pathol. 2009;217(5):716–27.

    Article  CAS  PubMed  Google Scholar 

  56. Elco CP, Mariño-Enríquez A, Abraham JA, Dal Cin P, Hornick JL. Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor: report of a case providing further evidence for a pathogenetic link. Am J Surg Pathol. 2010;34(11):1723–7.

    PubMed  Google Scholar 

  57. Lambert I, Debiec-Rychter M, Guelinckx P, Hagemeijer A, Sciot R. Acral myxoinflammatory fibroblastic sarcoma with unique clonal chromosomal changes. Virchows Arch. 2001;438(5):509–12.

    Article  CAS  PubMed  Google Scholar 

  58. Antonescu CR, Zhang L, Nielsen GP, Rosenberg AE, Dal Cin P, 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(10):757–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mansoor A, Fidda N, Himoe E, Payne M, Lawce H, Magenis RE. Myxoinflammatory fibroblastic sarcoma with complex supernumerary ring chromosomes composed of chromosome 3 segments. Cancer Genet Cytogenet. 2004;152(1):61–5.

    Article  CAS  PubMed  Google Scholar 

  60. West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, et al. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A. 2006;103(3):690–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Panagopoulos I, Brandal P, Gorunova L, Bjerkehagen B, Heim S. Novel CSF1-S100A10 fusion gene and CSF1 transcript identified by RNA sequencing in tenosynovial giant cell tumors. Int J Oncol. 2014;44(5):1425–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 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(1):21–9.

    Article  CAS  PubMed  Google Scholar 

  63. 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(11):1417–25.

    Article  PubMed  Google Scholar 

  64. Carter JM, Sukov WR, Montgomery E, Goldblum JR, Billings SD, Fritchie KJ, Folpe AL. TGFBR3 and MGEA5 rearrangements in pleomorphic hyalinizing angiectatic tumors and the spectrum of related neoplasms. Am J Surg Pathol. 2014;38(9):1182–992.

    Article  PubMed  Google Scholar 

  65. Wei S, Pan Z, Siegal GP, Winokur TS, Carroll AJ, Jhala D. Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts. Hum Pathol. 2012;43(1):121–6.

    Article  CAS  PubMed  Google Scholar 

  66. Mohajeri A, Kindblom LG, Sumathi VP, Brosjö O, Magnusson L, Nilsson J, et al. SNP array and FISH findings in two pleomorphic hyalinizing angiectatic tumors. Cancer Genet. 2012;205(12):673–6.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Laboratory Medicine Program, University Health Network, 200 Elizabeth St., Toronto, ON, Canada, M5G 2C4

    Danny Ghazarian MB, ChB, PhD, FRCPC

  2. Department of Pathology, CHU-L’Hotel-Dieu de Quebec, 11 Cote du Palais, Quebec, QC, Canada, G1R 2J6

    Sebastien Labonte MD, FRCP(C)

  3. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Suite 6.500.12.5, Toronto, ON, Canada, M5G 1X5

    Brendan Craig Dickson BA, BSc, MD, MSc, FCAP, FRCP(C)

  4. Department of Laboratory Medicine and Pathobiology, University Health Network, UHN, Eaton Wing, 11th Floor, 200 Elizabeth Street, Toronto, ON, Canada, M5G 2C4

    Ayman Al Habeeb MBBS, FRCPC

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  1. Danny Ghazarian MB, ChB, PhD, FRCPC
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  2. Sebastien Labonte MD, FRCP(C)
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  3. Brendan Craig Dickson BA, BSc, MD, MSc, FCAP, FRCP(C)
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  4. Ayman Al Habeeb MBBS, FRCPC
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Correspondence to Danny Ghazarian MB, ChB, PhD, FRCPC .

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Editors and Affiliations

  1. Miraca Life Sciences, Dermatopathology Division, Dallas, Texas, USA

    Jose A. Plaza

  2. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Victor G. Prieto

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Ghazarian, D., Labonte, S., Dickson, B.C., Al Habeeb, A. (2016). Immunohistology and Molecular Studies of Fibrohistiocytic and Myofibroblastic Cutaneous Tumors. In: Plaza, J., Prieto, V. (eds) Applied Immunohistochemistry in the Evaluation of Skin Neoplasms. Springer, Cham. https://doi.org/10.1007/978-3-319-30590-5_6

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