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Solitary fibrous tumour presenting with a single bone metastasis: report of six cases and literature review

Solitary fibrous tumour presenting with a single bone metastasis: report of six cases and... Background: Solitary fibrous tumour (SFT ) is a rare soft tissue sarcoma with a low metastatic potential. A higher metastatic rate is observed in the high-grade/dedifferentiated variant. The most common expected site of distant spread are the lungs and the liver. Bone involvement is generally viewed as a late stage of disease spread. We report on a retrospective series of SFT patients relapsing with a single distant bone recurrence as first metastatic event, with- out evidence of other organ involvement. Case presentation: All patients affected by a single distant bone metastasis from SFT as first distant event, without any evidence of other site of metastasis, observed at our Institution, were considered. Bone involvement from SFT was pathologically assessed in all cases and confirmed by expert pathologists. A total of six patients were retrospec- tively identified. Primary tumour arose from the meninges in four patients, from soft tissues in two. Bone metastases were located to the vertebrae, the hip, the acetabulum and the rib. In all cases, bone relapse was the first event, with one patient presenting a local relapse. Median time from the primary tumour and the evidence of bone relapse was 40 months (range 0–58). In 2/6 patients bone metastasis was treated with radiotherapy (RT ), in 2/6 with surgery, in 2/6 with surgery plus RT. At a median follow-up of 55 months (range 23–88), 5/6 patients are alive (2/5 without disease, 3/5 with multicentric metastatic disease) and one is dead of disease. 2/6 patients did not relapse after the treatment of the bone metastasis. Conclusions: This small series in a relatively rare histology suggests that isolated, possibly late, bone metastases are a plausible scenario, in particular in meningeal SFT. Notably, new bone lesions in a patient with a history of SFT should be always investigated. Exclusive local treatments may be an option, though collection of such series would be needed to define the best treatment strategy. Keywords: Sarcoma, Solitary fibrous tumour, Hemangiopericytoma, Metastasis, Prognosis, Bone Background Recently also primary SFTs arising from the bone have Solitary fibrous tumour (SFT) is a very rare sarcoma, been reported [4]. SFT is characterized by a specific most frequently occurring in middle-aged patients. SFT NAB2–STAT6 gene fusion which is responsible for the can occur in several anatomic sites like meninges, peri- nuclear expression of the chimeric oncoprotein STAT6, toneum, head and neck, extremities, and viscera [1–3]. which is the immunohistochemical hallmark of SFT [5–8] and helps in differential diagnosis. Of note, dedifferenti - ated SFT may lose the protein expression while retaining *Correspondence: vittoria.colia@istitutotumori.mi.it 1 the fusion gene [9]. SFTs are known for the low tendency Adult Mesenchymal Tumour & Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale of recurrence and the low metastatic potential after com- Tumori, via G. Venezian, 1, 20133 Milan, Italy plete resection (10–15 %), even if a higher metastatic rate Full list of author information is available at the end of the article © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Colia et al. Clin Sarcoma Res (2016) 6:16 Page 2 of 6 (40  %) has been described in case of pleomorphic/dedi- lesions were all consistent with a diagnosis of malignant er ff entiated SFT [10, 11]. Recurrence may happen many SFT, with evidence of progression from a classic SFT years after the initial diagnosis [12]. As for all other sar- towards a malignant SFT in one (Figs. 2,3). comas, the most frequent and initial site of metastasis Bone metastases were mainly detected by the clinical is the lung, followed by the liver [13]. Bone involvement complaint of pain, since a bone scan was not foreseen in is reported in the late phase of the disease, in patients the follow-up plan of these patients. Median time from already affected by lung lesions [12]. the primary tumour diagnosis and the evidence of bone We report on a retrospective series of SFT patients relapse was 40  months (range 0–58). In five cases, bone who suffered from a single distant bone recurrence as relapse was the first event while one patient presented their first metastatic event, without evidence of any other with a synchronous single bone lesion (case 6 in Table 1). organ involvement. All the patients received a definitive treatment of the bone lesion, with curative intent. A complete surgical Case presentation resection of the bone metastasis was performed in four From May 2014 to April 2016 at the Fondazione IRCCS cases, followed by complementary radiotherapy in two Istituto Nazionale Tumori Milan, Italy, we observed cases. Radiotherapy was given in two cases. five patients with a diagnosis of SFT relapsed with sin - At a median follow-up of 55  months (range 23–88), gle bone metastasis plus an additional case whose bone five of six patients are alive (2/5 without disease, 3/5 metastasis was synchronous to the primary tumour. with multicentric metastatic disease) and one is dead of Bone involvement from SFT was pathologically disease. Two of six patients (one treated with definitive assessed in all cases and final diagnosis of bone relapse RT and one with surgery plus RT) did not suffer of any from SFT was confirmed by expert pathologists bas - tumour relapse after the treatment of the bone metasta- ing on morphologic and immunohistochemical features, sis, at a follow-up of 51 and 56 months (Table 1). with STAT6 nuclear immunopositivity, and by compar- ing the metastatic tissue with the primary tumour. Discussion Disease status was assessed in all the patients by whole This retrospective analysis reports on a series of six body CT scan, MRI and/or CT of the primary tumour patients affected by a single solitary bone metastasis site. A bone scan ruled out the presence of other meta- from SFT as first metastatic event. This small series in a static bone lesions (Fig. 1). relatively rare histology shows that isolated, possibly late, Patient characteristics are summarized in Table  1. Pri- bone metastases are a plausible scenario, in particular in mary SFT arose from the meninges in four patients, while meningeal SFTs. in the soft tissues of the left thigh and left gluteus in two. All patients were treated with a curative intent. Two of Pathological centralized review of the primary tumour them are still disease free at 51 and 56 months. confirmed a diagnosis of malignant SFT in all the cases In the literature, the most common sites of metastasis but one that was consistent with a classic SFT. The bone in SFT patients were reported to be the lung and the liver [12, 14–31]. In addition, there are few case reports of SFTs, mostly arising from the meninges and pleura, pre- senting with multiple late distant bone metastases that followed the prior evidence of lesions located to the lung and to the liver. To our knowledge there are only two reports of SFTs relapsed with a single late bone metas- tasis and no extra-skeletal [32, 33]. Notably in both cases primary tumour was located to the meninges. Our study confirms that isolated bone metastasis can occur in SFT. To note, in our series, in two of four cases the primitive tumour arose from the soft tissue. Recently also primary SFT arising from the bone have been reported [26]. In case of a single bone lesion con- sistent with SFT a past or present primary tumour needs always to be ruled out. In our series, median time from the primary tumour Fig. 1 Single bone metastasis from meningeal SFT (patient 1 in and the appearance of bone relapse was about 3  years, Table 1): CT scan (venous phase after contrast medium) shows a solid while published cases are reported after a long interval lesion characterized by homogeneous contrast enhancement at the level of the seventh left rib from the primary [32, 33]. Colia et al. Clin Sarcoma Res (2016) 6:16 Page 3 of 6 Table 1 Patient clinical characteristics and tumour histopathological and immunohistochemical features Case no Age/sex Primary tumour Bone metastasis Further relapse Status OS at last (months) Site Diagnosis STAT6 Surgery RT Fist distant Path IHC Time Treatment Site Time follow-up (IHC) relapse diagnosis STAT6 from pri- of relapse to relapse mary from bone and bone met relapse (month) 1 38/M Meninges Malignant SFT Pos Yes No 7° left rib Malignant SFT Pos 50 Complete Bone 84 AWD 88 surgery 2 40/M Meninges Malignant SFT Pos* Yes Yes S3–S4 Malignant SFT Pos 27 palliative RT Bone and 30 AWD 35 vertebra lung 3 24/M Meninges Malignant SFT Pos* Yes Yes Hipbone Malignant SFT Pos 58 Complete Bone 78 AWD 79 surgery and RT 4 26/F Meninges Malignant SFT Pos Yes Yes C4–C5 verte- Malignant SFT Pos 48 Complete NA NA NED 51 brae surgery and RT 5 71/F Deep soft Malignant SFT Pos Yes No Left acetabu- Malignant SFT Pos 54 Definitive RT NA NA NED 56 tissue of left lum thigh 6 66/M Deep soft Classic SFT Pos Yes No 4° right rib Malignant Pos* 0 Complete Lung 12 DOD 23 tissue of left SFT surgery gluteus Colia et al. Clin Sarcoma Res (2016) 6:16 Page 4 of 6 In addition, in one of the two cases, the selected treat- ment was definitive RT alone suggesting that radiation treatment can be an alternative to surgery when mor- bidity is an issue. No patients received a systemic treat- ment for the single bone lesion; chemotherapy was given later in two patients who relapsed to multiple sites. SFTs show a low sensitivity to conventional cytotoxic chemo- therapy [34, 35]. Recently, systemic therapy has focused on molecularly targeted therapies reporting some activ- ity of antiangiogenics (bevacizumab in combination with temozolomide, sorafenib, sunitinib and pazopanib) [35–37]. There is no consensus on the optimal routine follow-up policy of sarcomas [38]; although SFTs presenting with Fig. 2 Histopathological pattern of primary meningeal malignant a single bone metastasis seem to be relatively rare, this SFT (patient 3 Table 1). Tumour shows patternless growth of a series suggests that a bone scan should be included in uniform, bland, hypercellular, STAT6 positive, spindle cell proliferation the staging of SFT patients and in case of bone pain in a around characteristic thin walled branched vessel. STAT6 200× patient with a history of SFT. In one case we observed a bone lesion progressing towards a more aggressive variant of SFT. This underlies once more the limits of the classification available to date [39]. None of our cases showed, at the time of the skeletal progression, a biological shift towards a high-grade dedif- ferentiated SFT. However, some of the cases showed an initial loss of STAT6 nuclear positivity in the bone metas- tasis, suggestive for a more aggressive potential. It is now described in the literature that immunohistochemical positivity for STAT6 may be lost in some SFTs while the fusion NAB2–STAT6 is retained [9]. To rule-out SFT diagnosis in these cases the demonstration of transloca- tion is needed. Conclusion This small series in a rare sarcoma subtype suggests that Fig. 3 Histopathological pattern of hipbone metastasis from primary isolated, skeletal metastases are a possible event in both meningeal malignant SFT (patient 3 Table 1). Similarly to primary meningeal and extrameningeal SFTs. On this basis bone lesion, tumour growths with patternless architecture, around thin lesions or symptoms in a patient with a history of SFT walled vessel, with a more loose stroma, retaining immunoreactivity for STAT6. STAT6 200× should be always investigated. Potentially curative local treatments may be an option, although a larger series is needed to define the best treatment strategy for such patients. All our patients received a local treatment of the bone metastasis with a curative intent. This could be consid - Abbreviations ered an overtreatment as the standard of care of bone SFT: solitary fibrous tumour; CT scan: computerized tomography; MRI scan: metastasis is offered with a palliative intent. Curative sur - magnetic resonance imaging; RT: radiotherapy; CT: chemotherapy; IH: immu- gery was selected in four patients, followed by comple- nohistochemistry; NA: not applicable; M: months; Met: metastasis; Pos: nuclear positivity; *: negativity of isolated neoplastic cells; NED: no evidence of disease; mentary radiotherapy in two cases (cases 3, 4, Table  1), AWD: alive with disease; DOD: died of disease; OS: overall survival. while radiotherapy was given in two cases. However, it is interesting to note that in two cases with a prolonged Authors’ contributions VC and SP compiled the clinical data, reviewed the literature and drafted follow-up the tumour has not yet relapsed. Yet to be con- the manuscript. CM provided radiological data. SLR, PC and APDT provided firmed on a larger prospective series, this suggests that the pathologic data. AM reviewed and edited the manuscript. PGC offered in case of single bone metastasis a local treatment with conceptual advice, reviewed and edited the manuscript. SS compiled the clinical data, offered conceptual advice, guided the composition process, curative intent may be an option. Colia et al. Clin Sarcoma Res (2016) 6:16 Page 5 of 6 reviewed and edited the manuscript. All authors read and approved the final 14. Guillerme F, Truntzer P, Prim N, et al. Solitary fibrous tumors: case report of manuscript. a late relapse. Cancer Radiother. 2011;15:330–3. 15. Park CK, Lee DH, Park JY, et al. Multiple recurrent malignant solitary Author details fibrous tumors: long-term follow-up of 24 years. Ann Thorac Surg. Adult Mesenchymal Tumour & Rare Cancer Medical Oncology Unit, Cancer 2011;91:1285–8. Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, via G. 16. Mohamed H, Mandal AK. Natural history of multifocal solitary fibrous Venezian, 1, 20133 Milan, Italy. Department of Radiology and Radiotherapy, tumors of the pleura: a 25-year follow-up report. J Natl Med Assoc. Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Department 2004;96:659–62. of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto 17. Tzelepi V, Zolota V, Batistatou A, et al. Solitary fibrous tumor of the urinary Nazionale dei Tumori, Milan, Italy. Laboratory of Experimental Molecular bladder: report of a case with long-term follow-up and review of the Pathology, Department of Diagnostic Pathology and Laboratory Medicine, literature. Eur Rev Med Pharmacol Sci. 2007;11:101–6. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Department 18. Fujita I, Kiyama T, Chou K, et al. A case of metastatic hemangiopericytoma of Diagnostic Pathology, General Hospital, Treviso, Italy. Humanitas Cancer occurring 16 years after initial presentation: with special reference to the Center, Milan, Italy. clinical behavior and treatment of metastatic hemangiopericytoma. J Nihon Med Sch. 2009;76:221–5. Acknowledgements 19. Hiraki A, Murakami T, Aoe K, Matsuda E, et al. Recurrent superior medi- The authors thank the patients and their families. astinal primary hemangiopericytoma 23 years after the complete initial excision: a case report. Acta Med Okayama. 2006;60:197–200. Competing interests 20. Suzuki H, Haga Y, Oguro K, et al. Intracranial hemangiopericytoma The authors declare that they have no competing interests. with extracranial metastasis occurring after 22 years. Neurol Med Chir. 2002;42:297–300. Availability of data and supporting materials 21. Han N, Kim H, Min SK, et al. Meningeal solitary fibrous tumors with The authors are happy to share their data for research purpose. Please contact delayed extracranial metastasis. J Pathol Transl Med. 2016;50(2):113–21. the corresponding author in case. 22. Someya M, Sakata KI, Oouchi A, Nagakura H, Satoh M, Hareyama M. Four cases of meningeal hemangiopericytoma treated with sur-gery and Consent for publication radiotherapy. Jpn J Clin Oncol. 2001;31:548–52. Written informed consent was obtained from the patients for publication of 23. Dufour H, Métellus P, Fuentes S, et al. Meningeal hemangiopericy-toma: this Case Report and any accompanying images. a retrospective study of 21 patients with special review of postoperative external radiotherapy. Neurosurgery. 2001;48:756–62. Received: 3 June 2016 Accepted: 6 August 2016 24. Pistolesi S, Fontanini G, Barellini L, et al. Meningeal hemangioperi-cytoma metastatic to the adrenal gland with multiple metastases to bones and lungs: a case report. Tumori. 2004;90:147–50. 25. Chang CC, Chang YY, Lui CC, Huang CC, Liu JS. Meningeal hemangio- pericytoma with delayed multiple distant metastases. J Chin Med Assoc. 2004;67:527–32. References 26. Ambrosini-Spaltro A, Eusebi V. Meningeal hemangiopericytomas and 1. Klemperer P, Rabin CB. Primary neoplasms of the pleura: a report of five hemangiopericytoma/solitary fibrous tumors of extracranial soft tissues: a cases. Arch Pathol. 1931;11:385–6. comparison. Virchows Arch. 2010;456:343–54. 2. Bikmaz K, Cosar M, Kurtkaya-Yapicier O, et al. Recurrent solitary fibrous 27. Mena H, Jorge L, Gholam H, et al. Hemangiopericytoma of the central tumour in the cerebellopontine angle. J Clin Neurosci. 2005;12:829–32. nervous system; a review of 94 cases. Hum Pathol. 1991;21:84–91. 3. Chan JKC. Solitary fibrous tumour—everywhere, and a diagnosis in 28. Guthrie BL, Ebersold MJ, Scheithauer BW, et al. Meningeal hemangioperi- vogue. Histopathology. 1997;31:568–76. cytoma: histopathological features, treatment, and long-term follow-up 4. Verbeke SLJ, Christopher CDM, Path FRC, et al. A reappraisal of hemangio- of 44 cases. Neurosurgery. 1989;25:514–22. pericytoma of bone; analysis of cases reclassified as synovial sarcoma and 29. Mahmood A, Caccamo DV, Tomecek FJ, et al. Atypical and malig- solitary fibrous tumor of Bone. Am J Surg Pathol. 2010;34:777–83. nant meningiomas: a clinicopathological review. Neurosurgery. 5. Chmielecki J, Crago AM, Rosenberg M, et al. Whole-exome sequencing 1993;33:955–63. identifies a recurrent NAB2–STAT6 fusion in solitary fibrous tumors. Nat 30. Prakasha B, Jacob R, Dawson A, et al. Haemangiopericytoma diagnosed Genet. 2013;45:131–2. from a metastasis 11 years after surgery for “atypical meningioma”. Br J 6. Robinson DR, Wu YM, Kalyana-Sundaram S, et al. Identification of recur - Radiol. 2001;74:856–8. rent NAB2–STAT6 gene fusions in solitary fibrous tumor by integrative 31. Wu Z, Yang H, Weng D, et al. Rapid recurrence and bilateral lungs, sequencing. Nat Genet. 2013;45:180–5. multiple bone metastasis of malignant solitary fibrous tumor of the right 7. Doyle LA, Vivero M, Fletcher CD, et al. Nuclear expression of STAT6 occipital lobe: report of a case and review. Diagn Pathol. 2015;10:91. distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol. 32. Nakada S, Minato H, Takegami T, et al. NAB2–STAT6 fusion gene analysis 2014;27:390–5. in two cases of meningeal solitary fibrous tumor/hemangiopericytoma 8. Yoshida A, Tsuta K, Ohno M, et al. STAT6 immunohistochemistry is with late distant metastases. Brain Tumor Pathol. 2015;32:268–74. helpful in the diagnosis of solitary fibrous tumors. Am J Surg Pathol. 33. Hoshi M, Araki N, Naka N, et al. Bone metastasis of intracranial meningeal 2014;38:552–9. hemangiopericytoma. Int J Clin Oncol. 2005;10:208–13. 9. Dagrada GP, Spagnuolo RD, Mauro V, et al. Solitary fibrous tumors: loss of 34. Stacchiotti S, Libertini M, Negri T, et al. Response to chemotherapy chimeric protein expression and genomic instability mark dedifferentia- of solitary fibrous tumour: a retrospective study. Eur J Cancer. tion. Mod Pathol. 2015;28(8):1074–83. 2013;49(10):2376–83. 10. Magro G, Emmanuele C, Lopes M, et al. Solitary fibrous tumour of the 35. Colia V, Provenzano S, Hindi N, et al. Systemic therapy for selected skull kidney with sarcomatous overgrowth. Case report and review of the base sarcomas: chondrosarcoma, chordoma, giant cell tumour and literature. Apmis. 2008;116(11):1020–5. solitary fibrous tumor/hemangiopericytoma. Rep Pract Oncol Radiother. 11. Beadle GF, Hillcaot BL. Treatment of advanced malignant hemangioperi- 2016;21(4):361–9. cytoma with combination adriamycin and DTIC: a report of four cases. J 36. Stacchiotti S, Negri T, Palassini E, et al. Sunitinib malate and figitumumab Surg Oncol. 1983;22:167–70. in solitary fibrous tumor: patterns and molecular bases of tumor 12. Baldi GG, Stacchiotti S, Mauro V, et al. Solitary fibrous tumor of all sites: response. Mol Cancer Ther. 2010;9(5):1286–97. outcome of late recurrences in 14 patients. Clin Sarcoma Res. 2013;3:4. 37. Park MS, Patel SR, Ludwig JA, et al. Activity of temozolomide and beva- 13. The ESMO/European sarcoma network working group. Bone sarcomas: cizumab in the treatment of locally advanced, recurrent, and metastatic ESMO clinical practice guidelines for diagnosis, treatment and follow-up. hemangiopericytoma and malignant solitary fibrous tumor. Cancer. Ann Oncol. 2014;25(Suppl 3):13–23. 2011;117(21):4939–47. Colia et al. Clin Sarcoma Res (2016) 6:16 Page 6 of 6 38. ESMO/European sarcoma network working group. Soft tissue and visceral 39. Fletcher CDM, Bridge JA, Hogendoorn P, et al. World Health Organization sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and ( WHO) classification of tumours of soft tissue and bone. Pathology and follow-up. Ann Oncol. 2014;25(Suppl 3):102–12. genetics. Lyon: IARC Press; 2013. 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Solitary fibrous tumour presenting with a single bone metastasis: report of six cases and literature review

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Springer Journals
Copyright
Copyright © 2016 by The Author(s)
Subject
Biomedicine; Cancer Research; Oncology; Surgical Oncology
eISSN
2045-3329
DOI
10.1186/s13569-016-0055-1
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27588167
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Abstract

Background: Solitary fibrous tumour (SFT ) is a rare soft tissue sarcoma with a low metastatic potential. A higher metastatic rate is observed in the high-grade/dedifferentiated variant. The most common expected site of distant spread are the lungs and the liver. Bone involvement is generally viewed as a late stage of disease spread. We report on a retrospective series of SFT patients relapsing with a single distant bone recurrence as first metastatic event, with- out evidence of other organ involvement. Case presentation: All patients affected by a single distant bone metastasis from SFT as first distant event, without any evidence of other site of metastasis, observed at our Institution, were considered. Bone involvement from SFT was pathologically assessed in all cases and confirmed by expert pathologists. A total of six patients were retrospec- tively identified. Primary tumour arose from the meninges in four patients, from soft tissues in two. Bone metastases were located to the vertebrae, the hip, the acetabulum and the rib. In all cases, bone relapse was the first event, with one patient presenting a local relapse. Median time from the primary tumour and the evidence of bone relapse was 40 months (range 0–58). In 2/6 patients bone metastasis was treated with radiotherapy (RT ), in 2/6 with surgery, in 2/6 with surgery plus RT. At a median follow-up of 55 months (range 23–88), 5/6 patients are alive (2/5 without disease, 3/5 with multicentric metastatic disease) and one is dead of disease. 2/6 patients did not relapse after the treatment of the bone metastasis. Conclusions: This small series in a relatively rare histology suggests that isolated, possibly late, bone metastases are a plausible scenario, in particular in meningeal SFT. Notably, new bone lesions in a patient with a history of SFT should be always investigated. Exclusive local treatments may be an option, though collection of such series would be needed to define the best treatment strategy. Keywords: Sarcoma, Solitary fibrous tumour, Hemangiopericytoma, Metastasis, Prognosis, Bone Background Recently also primary SFTs arising from the bone have Solitary fibrous tumour (SFT) is a very rare sarcoma, been reported [4]. SFT is characterized by a specific most frequently occurring in middle-aged patients. SFT NAB2–STAT6 gene fusion which is responsible for the can occur in several anatomic sites like meninges, peri- nuclear expression of the chimeric oncoprotein STAT6, toneum, head and neck, extremities, and viscera [1–3]. which is the immunohistochemical hallmark of SFT [5–8] and helps in differential diagnosis. Of note, dedifferenti - ated SFT may lose the protein expression while retaining *Correspondence: vittoria.colia@istitutotumori.mi.it 1 the fusion gene [9]. SFTs are known for the low tendency Adult Mesenchymal Tumour & Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale of recurrence and the low metastatic potential after com- Tumori, via G. Venezian, 1, 20133 Milan, Italy plete resection (10–15 %), even if a higher metastatic rate Full list of author information is available at the end of the article © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Colia et al. Clin Sarcoma Res (2016) 6:16 Page 2 of 6 (40  %) has been described in case of pleomorphic/dedi- lesions were all consistent with a diagnosis of malignant er ff entiated SFT [10, 11]. Recurrence may happen many SFT, with evidence of progression from a classic SFT years after the initial diagnosis [12]. As for all other sar- towards a malignant SFT in one (Figs. 2,3). comas, the most frequent and initial site of metastasis Bone metastases were mainly detected by the clinical is the lung, followed by the liver [13]. Bone involvement complaint of pain, since a bone scan was not foreseen in is reported in the late phase of the disease, in patients the follow-up plan of these patients. Median time from already affected by lung lesions [12]. the primary tumour diagnosis and the evidence of bone We report on a retrospective series of SFT patients relapse was 40  months (range 0–58). In five cases, bone who suffered from a single distant bone recurrence as relapse was the first event while one patient presented their first metastatic event, without evidence of any other with a synchronous single bone lesion (case 6 in Table 1). organ involvement. All the patients received a definitive treatment of the bone lesion, with curative intent. A complete surgical Case presentation resection of the bone metastasis was performed in four From May 2014 to April 2016 at the Fondazione IRCCS cases, followed by complementary radiotherapy in two Istituto Nazionale Tumori Milan, Italy, we observed cases. Radiotherapy was given in two cases. five patients with a diagnosis of SFT relapsed with sin - At a median follow-up of 55  months (range 23–88), gle bone metastasis plus an additional case whose bone five of six patients are alive (2/5 without disease, 3/5 metastasis was synchronous to the primary tumour. with multicentric metastatic disease) and one is dead of Bone involvement from SFT was pathologically disease. Two of six patients (one treated with definitive assessed in all cases and final diagnosis of bone relapse RT and one with surgery plus RT) did not suffer of any from SFT was confirmed by expert pathologists bas - tumour relapse after the treatment of the bone metasta- ing on morphologic and immunohistochemical features, sis, at a follow-up of 51 and 56 months (Table 1). with STAT6 nuclear immunopositivity, and by compar- ing the metastatic tissue with the primary tumour. Discussion Disease status was assessed in all the patients by whole This retrospective analysis reports on a series of six body CT scan, MRI and/or CT of the primary tumour patients affected by a single solitary bone metastasis site. A bone scan ruled out the presence of other meta- from SFT as first metastatic event. This small series in a static bone lesions (Fig. 1). relatively rare histology shows that isolated, possibly late, Patient characteristics are summarized in Table  1. Pri- bone metastases are a plausible scenario, in particular in mary SFT arose from the meninges in four patients, while meningeal SFTs. in the soft tissues of the left thigh and left gluteus in two. All patients were treated with a curative intent. Two of Pathological centralized review of the primary tumour them are still disease free at 51 and 56 months. confirmed a diagnosis of malignant SFT in all the cases In the literature, the most common sites of metastasis but one that was consistent with a classic SFT. The bone in SFT patients were reported to be the lung and the liver [12, 14–31]. In addition, there are few case reports of SFTs, mostly arising from the meninges and pleura, pre- senting with multiple late distant bone metastases that followed the prior evidence of lesions located to the lung and to the liver. To our knowledge there are only two reports of SFTs relapsed with a single late bone metas- tasis and no extra-skeletal [32, 33]. Notably in both cases primary tumour was located to the meninges. Our study confirms that isolated bone metastasis can occur in SFT. To note, in our series, in two of four cases the primitive tumour arose from the soft tissue. Recently also primary SFT arising from the bone have been reported [26]. In case of a single bone lesion con- sistent with SFT a past or present primary tumour needs always to be ruled out. In our series, median time from the primary tumour Fig. 1 Single bone metastasis from meningeal SFT (patient 1 in and the appearance of bone relapse was about 3  years, Table 1): CT scan (venous phase after contrast medium) shows a solid while published cases are reported after a long interval lesion characterized by homogeneous contrast enhancement at the level of the seventh left rib from the primary [32, 33]. Colia et al. Clin Sarcoma Res (2016) 6:16 Page 3 of 6 Table 1 Patient clinical characteristics and tumour histopathological and immunohistochemical features Case no Age/sex Primary tumour Bone metastasis Further relapse Status OS at last (months) Site Diagnosis STAT6 Surgery RT Fist distant Path IHC Time Treatment Site Time follow-up (IHC) relapse diagnosis STAT6 from pri- of relapse to relapse mary from bone and bone met relapse (month) 1 38/M Meninges Malignant SFT Pos Yes No 7° left rib Malignant SFT Pos 50 Complete Bone 84 AWD 88 surgery 2 40/M Meninges Malignant SFT Pos* Yes Yes S3–S4 Malignant SFT Pos 27 palliative RT Bone and 30 AWD 35 vertebra lung 3 24/M Meninges Malignant SFT Pos* Yes Yes Hipbone Malignant SFT Pos 58 Complete Bone 78 AWD 79 surgery and RT 4 26/F Meninges Malignant SFT Pos Yes Yes C4–C5 verte- Malignant SFT Pos 48 Complete NA NA NED 51 brae surgery and RT 5 71/F Deep soft Malignant SFT Pos Yes No Left acetabu- Malignant SFT Pos 54 Definitive RT NA NA NED 56 tissue of left lum thigh 6 66/M Deep soft Classic SFT Pos Yes No 4° right rib Malignant Pos* 0 Complete Lung 12 DOD 23 tissue of left SFT surgery gluteus Colia et al. Clin Sarcoma Res (2016) 6:16 Page 4 of 6 In addition, in one of the two cases, the selected treat- ment was definitive RT alone suggesting that radiation treatment can be an alternative to surgery when mor- bidity is an issue. No patients received a systemic treat- ment for the single bone lesion; chemotherapy was given later in two patients who relapsed to multiple sites. SFTs show a low sensitivity to conventional cytotoxic chemo- therapy [34, 35]. Recently, systemic therapy has focused on molecularly targeted therapies reporting some activ- ity of antiangiogenics (bevacizumab in combination with temozolomide, sorafenib, sunitinib and pazopanib) [35–37]. There is no consensus on the optimal routine follow-up policy of sarcomas [38]; although SFTs presenting with Fig. 2 Histopathological pattern of primary meningeal malignant a single bone metastasis seem to be relatively rare, this SFT (patient 3 Table 1). Tumour shows patternless growth of a series suggests that a bone scan should be included in uniform, bland, hypercellular, STAT6 positive, spindle cell proliferation the staging of SFT patients and in case of bone pain in a around characteristic thin walled branched vessel. STAT6 200× patient with a history of SFT. In one case we observed a bone lesion progressing towards a more aggressive variant of SFT. This underlies once more the limits of the classification available to date [39]. None of our cases showed, at the time of the skeletal progression, a biological shift towards a high-grade dedif- ferentiated SFT. However, some of the cases showed an initial loss of STAT6 nuclear positivity in the bone metas- tasis, suggestive for a more aggressive potential. It is now described in the literature that immunohistochemical positivity for STAT6 may be lost in some SFTs while the fusion NAB2–STAT6 is retained [9]. To rule-out SFT diagnosis in these cases the demonstration of transloca- tion is needed. Conclusion This small series in a rare sarcoma subtype suggests that Fig. 3 Histopathological pattern of hipbone metastasis from primary isolated, skeletal metastases are a possible event in both meningeal malignant SFT (patient 3 Table 1). Similarly to primary meningeal and extrameningeal SFTs. On this basis bone lesion, tumour growths with patternless architecture, around thin lesions or symptoms in a patient with a history of SFT walled vessel, with a more loose stroma, retaining immunoreactivity for STAT6. STAT6 200× should be always investigated. Potentially curative local treatments may be an option, although a larger series is needed to define the best treatment strategy for such patients. All our patients received a local treatment of the bone metastasis with a curative intent. This could be consid - Abbreviations ered an overtreatment as the standard of care of bone SFT: solitary fibrous tumour; CT scan: computerized tomography; MRI scan: metastasis is offered with a palliative intent. Curative sur - magnetic resonance imaging; RT: radiotherapy; CT: chemotherapy; IH: immu- gery was selected in four patients, followed by comple- nohistochemistry; NA: not applicable; M: months; Met: metastasis; Pos: nuclear positivity; *: negativity of isolated neoplastic cells; NED: no evidence of disease; mentary radiotherapy in two cases (cases 3, 4, Table  1), AWD: alive with disease; DOD: died of disease; OS: overall survival. while radiotherapy was given in two cases. However, it is interesting to note that in two cases with a prolonged Authors’ contributions VC and SP compiled the clinical data, reviewed the literature and drafted follow-up the tumour has not yet relapsed. Yet to be con- the manuscript. CM provided radiological data. SLR, PC and APDT provided firmed on a larger prospective series, this suggests that the pathologic data. AM reviewed and edited the manuscript. PGC offered in case of single bone metastasis a local treatment with conceptual advice, reviewed and edited the manuscript. SS compiled the clinical data, offered conceptual advice, guided the composition process, curative intent may be an option. Colia et al. Clin Sarcoma Res (2016) 6:16 Page 5 of 6 reviewed and edited the manuscript. All authors read and approved the final 14. Guillerme F, Truntzer P, Prim N, et al. Solitary fibrous tumors: case report of manuscript. a late relapse. Cancer Radiother. 2011;15:330–3. 15. Park CK, Lee DH, Park JY, et al. Multiple recurrent malignant solitary Author details fibrous tumors: long-term follow-up of 24 years. Ann Thorac Surg. Adult Mesenchymal Tumour & Rare Cancer Medical Oncology Unit, Cancer 2011;91:1285–8. Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, via G. 16. 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Clinical Sarcoma ResearchSpringer Journals

Published: Sep 1, 2016

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