Skip to main content

Advertisement

SpringerLink
Log in

Clinicopathological review of solitary fibrous tumors: dedifferentiation is a major cause of patient death

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Solitary fibrous tumor (SFT) is a soft-tissue neoplasm of intermediate malignant potential, presenting a wide histopathological spectrum. Poorer prognosis of hemangiopericytoma of the central nervous system (CNS), hypoglycemic SFT, and dedifferentiation are well-known characters of SFT, but their clinical significance were not demonstrated enough by large-sized study. Here, the clinicopathological features of SFTs are reviewed and the relationship between genetics and clinicopathological features is examined using 145 SFT cases. All cases were STAT6 IHC-positive and/or NAB2-STAT6 fusion gene-positive. Tumor location was classified into three categories: 30 pleuropulmonary, 96 non-pleuropulmonary/non-central nervous system (CNS), and 18 CNS tumors. The tumor developed recurrence in 21 of 93 available cases (22.5%), metastasis in 11 of 93 (11.8%), and tumor death in 9 of 93 (9.6%). Hypoglycemia occurred in 2 primary tumors and 1 metastatic tumor among 63 reviewable cases, and dedifferentiation occurred in 10 cases (6.8%) including 6 primary tumors, 2 recurrent tumors, and 2 metastatic tumors. Recurrence was positively associated with CNS location (p = 0.0109) and hypoglycemia (p = 0.001); metastasis was positively associated with CNS location (p = 0.0231), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001), while metastasis was negatively correlated with pleural location (p = 0.0471). Tumor death was positively associated with male sex (p = 0.0154), larger size (p = 0.0455), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001). Multivariate analysis revealed independent statistical significance of dedifferentiation for overall survival (p = 0.0467). Exon variant of the fusion gene had no statistical correlation with clinical outcome. In conclusion, dedifferentiation is a major prognostic factor of SFT, and specific location such as cerebromeningeal and intra-abdominal site and hypoglycemia also had a high risk for unfavorable prognosis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Guillou L, Fletcher JA, Fletcher CDM, Bridge JA, Lee J-C (2013) Extrapleural solitary fibrous tumor and haemangiopericytoma. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds) World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon, France, pp 80–82

    Google Scholar 

  2. 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 45:180–185

    Article  CAS  Google Scholar 

  3. 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 45:131–132

    Article  CAS  Google Scholar 

  4. Schweizer L, Koelsche C, Sahm F, Piro RM, Capper D, Reuss DE, Pusch S, Habel A, Meyer J, Göck T, Jones DTW, 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 125:651–658

    Article  CAS  Google Scholar 

  5. Doyle LA, Vivero M, Fletcher CD, Mertens F, Hornick JL (2014) Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol 27:390–395

    Article  CAS  Google Scholar 

  6. 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 38:552–559

    Article  Google Scholar 

  7. Koelsche C, Schweizer L, Renner M, Warth A, Jones DTW, Sahm F, Reuss DE, Capper D, Knösel T, Schulz B, Petersen I, Ulrich A, Renker EK, Lehner B, Pfister SM, Schirmacher P, von Deimling A, Mechtersheimer G (2014) Nuclear relocation of STAT6 reliably predicts NAB2-STAT6 fusion for the diagnosis of solitary fibrous tumour. Histopathology. 65:613–622

    Article  Google Scholar 

  8. Tai HC, Chuang IC, Chen TC, Li CF, Huang SC, Kao YC, Lin PC, Tsai JW, Lan J, Yu SC, Yen SL, Jung SM, Liao KC, Fang FM, Huang HY (2015) NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors. Mod Pathol 28:1324–1335

    Article  CAS  Google Scholar 

  9. England DM, Hochholzer L, McCarthy MJ (1989) Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases. Am J Surg Pathol 13:640–658

    Article  CAS  Google Scholar 

  10. Enzinger FM, Smith BH (1976) Hemangiopericytoma. An analysis of 106 cases. Hum Pathol 7:61–82

    Article  CAS  Google Scholar 

  11. Mosquera JM, Fletcher CD (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 33:1314–1321

    Article  Google Scholar 

  12. Wen PY (2017) Huse JT. 2016 World Health Organization classification of central nervous system tumors. Continuum (Minneap Minn) 23(6, Neuro-oncology):1531–1547

    Google Scholar 

  13. Yamada Y, Kohashi K, Fushimi F, Takahashi Y, Setsu N, Endo M, Yamamoto H, Tokunaga S, Iwamoto Y, Oda Y (2014) Activation of the Akt-mTOR pathway and receptor tyrosine kinase in patients with solitary fibrous tumors. Cancer. 120:864–876

    Article  CAS  Google Scholar 

  14. Nguyen H, Briere J, Clavier J, Raut Y, Leroy JP, Verlingue R (1983) Five new cases of solitary fibrous mesothelioma of the visceral pleura. Poumon Coeur 39:167–174

    PubMed  CAS  Google Scholar 

  15. Witkin GB, Rosai J (1989) Solitary fibrous tumor of the mediastinum. A report of 14 cases. Am J Surg Pathol 13:547–557

    Article  CAS  Google Scholar 

  16. Roy TM, Burns MV, Overly DJ, Curd BT (1992) Solitary fibrous tumor of the pleura with hypoglycemia: the Doege-potter syndrome. J Ky Med Assoc 90:557–560

    PubMed  CAS  Google Scholar 

  17. Strøm EH, Skjørten F, Aarseth LB et al (1991) Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia. Pathol Res Pract 187:109–113 discussion 114–116

    Article  Google Scholar 

  18. Fukasawa Y, Takada A, Tateno M, Sato H, Koizumi M, Tanaka A, Sato T (1998) Solitary fibrous tumor of the pleura causing recurrent hypoglycemia by secretion of insulin-like growth factor II. Pathol Int 48:47–52

    Article  CAS  Google Scholar 

  19. Wakami K, Tateyama H, Kawashima H, Matsuno T, Kamiya Y, Jin-No Y, Kimura G, Eimoto T (2005) Solitary fibrous tumor of the uterus producing high-molecular-weight insulin-like growth factor II and associated with hypoglycemia. Int J Gynecol Pathol 24:79–84

    PubMed  Google Scholar 

  20. Doyle LA, Tao D, Mariño-Enríquez A (2014) STAT6 is amplified in a subset of dedifferentiated liposarcoma. Mod Pathol 27:1231–1237

    Article  CAS  Google Scholar 

  21. 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 184:1209–1218

    Article  CAS  Google Scholar 

  22. Demicco EG, Wagner MJ, Maki RG, Gupta V, Iofin I, Lazar AJ, Wang WL (2017) Risk assessment in solitary fibrous tumors: validation and refinement of a risk stratification model. Mod Pathol 30:1433–1442

    Article  Google Scholar 

  23. Demicco EG, Park MS, Araujo DM, Fox PS, Bassett RL, Pollock RE, Lazar AJ, Wang WL (2012) Solitary fibrous tumor: a clinicopathological study of 110 cases and proposed risk assessment model. Mod Pathol 25:1298–1306

    Article  Google Scholar 

  24. Akaike K, Kurisaki-Arakawa A, Hara K, Suehara Y, Takagi T, Mitani K, Kaneko K, Yao T, Saito T (2015) Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential. Hum Pathol 46:347–356

    Article  CAS  Google Scholar 

  25. Huang SC, Li CF, Kao YC, Chuang IC, Tai HC, Tsai JW, Yu SC, Huang HY, Lan J, Yen SL, Lin PC, Chen TC (2016) The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors. Cancer Med 5:159–168

    Article  CAS  Google Scholar 

  26. Chuang IC, Liao KC, Huang HY, Kao YC, Li CF, Huang SC, Tsai JW, Chen KC, Lan J, Lin PC (2016) NAB2-STAT6 gene fusion and STAT6 immunoexpression in extrathoracic solitary fibrous tumors: the association between fusion variants and locations. Pathol Int 66:288–296

    Article  CAS  Google Scholar 

  27. Nakada S, Minato H, Nojima T (2016) Clinicopathological differences between variants of the NAB2-STAT6 fusion gene in solitary fibrous tumors of the meninges and extra-central nervous system. Brain Tumor Pathol 33:169–174

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Technical support for the experimental trials was provided by the following laboratory assistants: Motoko Tomita, Mami Nakamizo, Juri Godo, Miwako Ishii, Hisami Matsumoto, and Noriko Aoki. We also appreciate the technical assistance from staff at The Research Support Center, Kyushu University Graduate School of Medical Sciences.

Funding

This study was supported by a JSPS KAKEN Grant (No. 17K15645) and by funds from the Scholarship Program of the Takeda Science Foundation.

Author information

Authors and Affiliations

  1. Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka-ken, 812-8582, Japan

    Yuichi Yamada, Kenichi Kohashi, Izumi Kinoshita, Hidetaka Yamamoto, Takeshi Iwasaki, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yoshihiro Itou, Yutaka Koga, Mikiko Hashisako, Yui Nozaki, Daisuke Kiyozawa, Daichi Kitahara & Yoshinao Oda

  2. Department of Pathology, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori, Miyakojima-ku, Osaka-shi, Osaka-fu, 534-0021, Japan

    Takeshi Inoue

  3. Department of Pathology, Kouseiren Takaoka Hospital, 5-10 Eiraku-machi, Takaoka-shi, Toyama-ken, 933-8555, Japan

    Munenori Mukai

  4. Department of Surgical Pathology, Kumamoto University Hospital, 2-39-1 Kurokami, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 860-8555, Japan

    Yumi Honda

  5. Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka-ken, 812-8582, Japan

    Gouji Toyokawa

  6. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka-ken, 812-8582, Japan

    Kenji Tsuchihashi

  7. Department of Pathology, Chidoribashi Hospital, 5-18-1 Chiyo, Hakata-ku, Fukuoka-shi, Fukuoka-ken, 812-0044, Japan

    Yoshifumi Matsushita

  8. Department of Pathology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, 3-23-1 Shiobaru, Minami-ku, Fukuoka-shi, Fukuoka-ken, 815-8588, Japan

    Fumiyoshi Fushimi

  9. Department of Pathology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka-shi, Fukuoka-ken, 811-1395, Japan

    Kenichi Taguchi

  10. Department of Pathology, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokurakita-ku, Kitakyushu-shi, Fukuoka-ken, 802-0077, Japan

    Sadafumi Tamiya

  11. Department of Pathology, Matsuyama Red Cross Hospital, 1 Bunkyomachi, Matsuyama-shi, Ehime-ken, 790-8524, Japan

    Yumi Oshiro

  12. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka-ken, 812-8582, Japan

    Masutaka Furue

  13. Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka-ken, 812-8582, Japan

    Yasuharu Nakashima

  14. Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka-ken, 812-8582, Japan

    Satoshi Suzuki & Toru Iwaki

Authors
  1. Yuichi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenichi Kohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Izumi Kinoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hidetaka Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takeshi Iwasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masato Yoshimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shin Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu Toda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshihiro Itou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yutaka Koga
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mikiko Hashisako
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yui Nozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Daisuke Kiyozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Daichi Kitahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Takeshi Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Munenori Mukai
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Yumi Honda
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Gouji Toyokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Kenji Tsuchihashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Yoshifumi Matsushita
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Fumiyoshi Fushimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Kenichi Taguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Sadafumi Tamiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Yumi Oshiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Masutaka Furue
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Yasuharu Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Satoshi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Toru Iwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Yoshinao Oda
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Yuichi Yamada performed the research and wrote the paper. Kenichi Kohashi, Izumi Kinoshita, Hidetaka Yamamoto and Takeshi Iwasaki contributed to the research design and slide review. Shin Ishihara, Yu Toda, Yoshihiro Itou, Yutaka Koga, Mikiko Hashisako, Yui Nozaki, Daisuke Kiyozawa, Daichi Kitahara, Takeshi Inoue, Munenori Mukai, Yumi Honda, Gouji Toyokawa, Kenji Tsuchihashi, Yoshifumi Matsushita, Fumiyoshi Fushimi, Kenichi Taguchi, Sadafumi Tamiya, Yumi Oshiro, Masutaka Furue, Yasuharu Nakashima, Satoshi Suzuki, and Toru Iwaki contributed to the sample collection and research design. Yoshinao Oda designed the research and gave final approval of the manuscript. All authors critically reviewed and approved the manuscript.

Corresponding author

Correspondence to Yoshinao Oda.

Ethics declarations

This study was conducted in accordance with the principles embodied in the Declaration of Helsinki. The study was also approved by the Ethics Committee of Kyushu University (Nos. 25-111, 25-143). Informed consent was obtained from the subjects or guardians.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PNG 1925 kb)

ESM 2

(DOCX 13 kb)

ESM 3

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamada, Y., Kohashi, K., Kinoshita, I. et al. Clinicopathological review of solitary fibrous tumors: dedifferentiation is a major cause of patient death. Virchows Arch 475, 467–477 (2019). https://doi.org/10.1007/s00428-019-02622-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-019-02622-9

Keywords

Search

Navigation