Virchows Archiv

, Volume 465, Issue 5, pp 615–621 | Cite as

A case of dedifferentiated solitary fibrous tumor in the pelvis with TP53 mutation

  • Aiko Kurisaki-Arakawa
  • Keisuke Akaike
  • Kieko Hara
  • Atsushi Arakawa
  • Michiko Takahashi
  • Keiko Mitani
  • Takashi Yao
  • Tsuyoshi Saito
Case Report


Solitary fibrous tumors (SFTs), initially observed in the pleura, were later found to develop in almost any extrapleural site. Dedifferentiation within SFTs was characterized only recently. We report a case of dedifferentiated SFT arising within the pelvis of a 70-year-old Japanese woman. Macroscopically, the resected tumor measured 17 × 17 × 13 cm. Histologically, the tumor displayed distinct heterologous osteosarcomatous and chondrosarcomatous components on a background of conventional SFT. Immunohistochemistry uncovered a loss of CD34 expression in the dedifferentiated area, whereas the nuclear expression of signal transducer and activator of transcription-6 (STAT6) and NGFI-A-binding protein 2 (NAB2) was maintained in both components. The p53 mutation 158 CGC > CAC (A158H) was found only in the dedifferentiated component. Furthermore, a fusion gene of NAB2(exon6)-STAT6(exon18) was detected in both the conventional and dedifferentiated components. The patient died of the disease 4 months after surgery. This case identifies a possible role of p53 dysfunction in the dedifferentiation process of SFT as reported in other sarcomas.


Solitary fibrous tumor STAT6 NAB2-STAT6 Dedifferentiation 



This work was supported in part by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, Sports and Culture (#26670286 to Tsuyoshi Saito), Tokyo, Japan.


  1. 1.
    Goodlad JR, Fletcher CD (1991) Solitary fibrous tumour arising at unusual sites: analysis of a series. Histopathology 19:515–522PubMedCrossRefGoogle Scholar
  2. 2.
    Hasegawa T, Matsuno Y, Shimoda T, Hasegawa F, Sano T, Hirohashi S (1999) Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behavior. Hum Pathol 30:1464–1473PubMedCrossRefGoogle Scholar
  3. 3.
    WHO Classification Tumours of Soft Tissue and Bone 2013, edited by Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. p.10. IARC Press World Health Organization International Agency for Research on CancerGoogle Scholar
  4. 4.
    Evans HL (1979) Liposarcoma: a study of 55 cases with a reassessment of its classification. Am J Surg Pathol 3:507–523PubMedCrossRefGoogle Scholar
  5. 5.
    Evans HL (2007) Atypical lipomatous tumor, its variants, and its combined forms: a study of 61 cases, with a minimum follow-up of 10 years. Am J Surg Pathol 31:1–14PubMedCrossRefGoogle Scholar
  6. 6.
    Dahlin DC, Beabout JW (1971) Dedifferentiation of low-grade chondrosarcomas. Cancer 28:461–466PubMedCrossRefGoogle Scholar
  7. 7.
    Frassica FJ, Unni KK, Beabout JW, Sim FH (1986) Dedifferentiated chondrosarcoma. A report of the clinicopathological features and treatment of seventy-eight cases. J Bone Joint Surg Am 68:1197–1205PubMedGoogle Scholar
  8. 8.
    Collini P, Negri T, Barisella M, Palassini E, Tarantino E, Pastorino U, Gronchi A, Stacchiotti S, Pilotti S (2012) High-grade sarcomatous overgrowth in solitary fibrous tumors: a clinicopathologic study of 10 cases. Am J Surg Pathol 36:1202–1215PubMedCrossRefGoogle Scholar
  9. 9.
    Mosquera JM, Fletcher CDM (2009) Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component—is this dedifferentiated SFT? Am J Surg Pathol 33:1314–1321PubMedCrossRefGoogle Scholar
  10. 10.
    Subramaniam MM, Lim XY, Venkateswaran K, Shuen CS, Soong R, Petersson F (2011) Dedifferentiated solitary fibrous tumour of the nasal cavity: the first case reported with molecular characterization of a TP53 mutation. Histopathology 59:1269–1274PubMedCrossRefGoogle Scholar
  11. 11.
    Doyle LA, Vivero M, Fletcher CD, Mertens F, Hornick JL (2014) Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol 27:390–395PubMedCrossRefGoogle Scholar
  12. 12.
    Schweizer L, Koelsche C, Sahm F, Piro RM, Capper D, Reuss DE, Pusch S, Habel A, Meyer J, Göck T, Jones DT, Mawrin C, Schittenhelm J, Becker A, Heim S, Simon M, Herold-Mende C, Mechtersheimer G, Paulus W, König R, Wiestler OD, Pfister SM, von Deimling A (2013) Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein. Acta Neuropathol 125:651–658PubMedCrossRefGoogle Scholar
  13. 13.
    Yoshida A, Tsuta K, Ohno M, Yoshida M, Narita Y, Kawai A, Asamura H, Kushima R (2014) STAT6 immunohistochemistry is helpful in the diagnosis of solitary fibrous tumors. Am J Surg Pathol 38:552–559PubMedCrossRefGoogle Scholar
  14. 14.
    Robinson DR, Wu YM, Kalyana-Sundaram S, Cao X, Lonigro RJ, Sung YS, Chen CL, Zhang L, Wang R, Su F, Iyer MK, Roychowdhury S, Siddiqui J, Pienta KJ, Kunju LP, Talpaz M, Mosquera JM, Singer S, Schuetze SM, Antonescu CR, Chinnaiyan AM (2013) Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet 45:180–185PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Chmielecki J, Crago AM, Rosenberg M, O’Connor R, Walker SR, Ambrogio L, Auclair D, McKenna A, Heinrich MC, Frank DA, Meyerson M (2013) Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet 45:131–132PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Mohajeri A, Tayebwa J, Collin A, Nilsson J, Magnusson L, von Steyern FV, Brosjö O, Domanski HA, Larsson O, Sciot R, Debiec-Rychter M, Hornick JL, Mandahl N, Nord KH, Mertens F (2013) Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor. Gene Chromosome Cancer 52:873–886CrossRefGoogle Scholar
  17. 17.
    Muller PA, Vousden KH (2013) p53 mutations in cancer. Nat Cell Biol 15:2–8PubMedCrossRefGoogle Scholar
  18. 18.
    Are C, Shaha AR (2006) Anaplastic thyroid carcinoma: biology, pathogenesis, prognosticfactors, and treatment approaches. Ann Surg Oncol 13:453–464PubMedCrossRefGoogle Scholar
  19. 19.
    Cheuk W, Chan JK, Ngan RK (1999) Dedifferentiation in adenoid cystic carcinoma of salivary gland: an uncommon complication associated with an accelerated clinical course. Am J Surg Pathol 23:465–472PubMedCrossRefGoogle Scholar
  20. 20.
    Kusafuka K, Takizawa Y, Ueno T, Ishiki H, Asano R, Kamijo T, Iida Y, Ebihara M, Ota Y, Onitsuka T, Kameya T (2008) Dedifferentiated epithelial-myoepithelial carcinoma of the parotid gland: a rare case report of immunohistochemical analysis and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106:85–91PubMedCrossRefGoogle Scholar
  21. 21.
    Schirosi L, Lantuejoul S, Cavazza A, Murer B, Yves Brichon P, Migaldi M, Sartori G, Sgambato A, Rossi G (2008) Pleuro-pulmonary solitary fibrous tumors: a clinicopathologic, immunohistochemical, and molecular study of 88 cases confirming the prognostic value of de Perrot staging system and p53 expression, and evaluating the role of c-kit, BRAF, PDGFRs (alpha/beta), c-met, and EGFR. Am J Surg Pathol 32:1627–1642PubMedCrossRefGoogle Scholar
  22. 22.
    Morimitsu Y, Nakajima M, Hisaoka M, Hashimoto H (2000) Extrapleural solitary fibrous tumor: clinicopathologic study of 17 cases and molecular analysis of the p53 pathway. APMIS 108:617–625, ReviewPubMedCrossRefGoogle Scholar
  23. 23.
    Tsuji S, Hisaoka M, Morimitsu Y, Hashimoto H, Shimajiri S, Komiya S, Ushijima M, Nakamura T (1998) Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues. Am J Pathol 153:1807–1812PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Saito T, Mitomi H, Izumi H, Suehara Y, Okubo T, Torigoe T, Takagi T, Kaneko K, Sato K, Matsumoto T, Yao T (2011) A case of secondary malignant giant-cell tumor of bone with p53 mutation after long-term follow-up. Hum Pathol 42:727–733PubMedCrossRefGoogle Scholar
  25. 25.
    Saito T, Mitomi H, Suehara Y, Okubo T, Torigoe T, Takagi T, Kaneko K, Yao T (2011) A case of denovo secondary malignant giant-cell tumor of bone with loss of heterozygosity of p53 gene that transformed within a short-term follow-up. Pathol Res Pract 207:664–669PubMedCrossRefGoogle Scholar
  26. 26.
    Gold JS, Antonescu CR, Hajdu C, Ferrone CR, Hussain M, Lewis JJ, Brennan MF, Coit DG (2002) Clinicopathologic correlates of solitary fibrous tumors. Cancer 94:1057–1068PubMedCrossRefGoogle Scholar
  27. 27.
    Masuda Y, Kurisaki-Arakawa A, Hara K, Arakawa A, Oh S, Suzuki K, Yao T, Saito T (2014) A case of dedifferentiated solitary fibrous tumor of the thoracic cavity. Int J Clin Exp Pathol 7:386–393PubMedPubMedCentralGoogle Scholar
  28. 28.
    Yokoi T, Tsuzuki T, Yatabe Y, Suzuki M, Kurumaya H, Koshikawa T, Kuhara H, Kuroda M, Nakamura N, Nakatani Y, Kakudo K (1998) Solitary fibrous tumour: significance of p53 and CD34 immunoreactivity in its malignant transformation. Histopathology 32:423–432PubMedCrossRefGoogle Scholar
  29. 29.
    Boyd C, McCluggage WG (2012) Low-grade ovarian serous neoplasms (low-grade serous carcinoma and serous borderline tumor) associated with high-grade serous carcinoma or undifferentiated carcinoma: report of a series of cases of an unusual phenomenon. Am J Surg Pathol 36:368–375PubMedCrossRefGoogle Scholar
  30. 30.
    Soares P, Lima J, Preto A, Castro P, Vinagre J, Celestino R, Couto JP, Prazeres H, Eloy C, Maximo V, Sobrinho-Simoes M (2011) Genetic alterations in poorly differentiated and undifferentiated thyroid carcinomas. Curr Genom 12:609–617CrossRefGoogle Scholar
  31. 31.
    Seethala RR, Hunt JL, Baloch ZW, Livolsi VA, Leon BE (2007) Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and review of the literature. Am J Surg Pathol 31:1683–1694PubMedCrossRefGoogle Scholar
  32. 32.
    Romero-Pérez L, López-García MÁ, Díaz-Martín J, Biscuola M, Castilla MÁ, Tafe LJ, Garg K, Oliva E, Matias-Guiu X, Soslow RA, Palacios J (2013) ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma. Mod Pathol 26:1514–1524PubMedCrossRefGoogle Scholar
  33. 33.
    Segura-Sánchez J, González-Cámpora R, Pareja-Megia MJ, García-Escudero A, Galera-Ruiz H, López-Beltrán A (2006) Chromosome-12 copy number alterations and MDM2, CDK4 and TP53 expression in soft tissue liposarcoma. Anticancer Res 26:4937–4942PubMedGoogle Scholar
  34. 34.
    Pilotti S, Della Torre G, Lavarino C, Di Palma S, Sozzi G, Minoletti F, Rao S, Pasquini G, Azzarelli A, Rilke F, Pierotti MA (1997) Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms. J Pathol 181:14–24PubMedCrossRefGoogle Scholar
  35. 35.
    Dei Tos AP, Doglioni C, Piccinin S, Maestro R, Mentzel T, Barbareschi M, Boiocchi M, Fletcher CD (1997) Molecular abnormalities of the p53 pathway in dedifferentiated liposarcoma. J Pathol 181:8–13PubMedCrossRefGoogle Scholar
  36. 36.
    Simms WW, Ordóñez NG, Johnston D, Ayala AG, Czerniak B (1995) p53 expression in dedifferentiated chondrosarcoma. Cancer 76:223–227PubMedCrossRefGoogle Scholar
  37. 37.
    Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y, Taya Y (2000) p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102:849–862PubMedCrossRefGoogle Scholar
  38. 38.
    Barthelmeß S, Geddert H, Boltze C, Moskalev EA, Bieg M, Sirbu H, Brors B, Wiemann S, Hartmann A, Agaimy A, Haller F (2014) Solitary fibrous tumors/hemangiopericytomas with different variants of the NAB2-STAT6 gene fusion are characterized by specific histomorphology and distinct clinicopathological features. Am J Pathol 184:1209–1218PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Aiko Kurisaki-Arakawa
    • 1
  • Keisuke Akaike
    • 1
  • Kieko Hara
    • 1
  • Atsushi Arakawa
    • 1
  • Michiko Takahashi
    • 1
  • Keiko Mitani
    • 1
  • Takashi Yao
    • 1
  • Tsuyoshi Saito
    • 1
  1. 1.Department of Human PathologyJuntendo University School of MedicineBunkyo-kuJapan

Personalised recommendations