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Purpose: To describe the imaging features of soft tissue solitary fibrous tumors, with histopathological correlations and clinical outcome. Material and methods: Twenty-seven patients with histologically proven SFTs were retrospectively evaluated. Imaging studies included six radiographs, five U/S studies, eighteen CT scans, fourteen MRI exams, and one angiography. Results: On CT scans, two lesions were isodense and five were mildly hypodense compared to muscle while 11 lesions appeared heterogeneous-mixed of iso and hypodense areas. Heterogeneous enhancement was depicted in 13 lesions and four lesions enhanced homogeneously. Six lesions were partially calcified. On T1W MR images, seven lesions were isointense and one was slightly hyperintense relative to adjacent muscles while five lesions appeared heterogeneous-mixed of iso and hypointense areas. T2W images showed high SI in two cases and heterogeneous- mixed in seven cases. Enhancement was heterogeneous in six and homogeneous in four lesions. Patchy unenhanced areas (on CT and T1W MR images) along with patchy areas of low to markedly high SI on T2W images were depicted in 19 lesions. The enhanced portions correlated to areas of increased vascularity and cellularity. The four clinically more aggressive lesions could not be predicted on imaging. Conclusion: Typical soft tissue SFTs are deep masses made of isodense and isointense areas relative to adjacent muscles mixed with hypodense and hypointense areas on unenhanced CT and MR T1W respectively. Variable enhancement patterns and mixed to high signal intensities on MRT2W are attributed to tumor’s cellularity, vascularity, collagen distribution and/or degeneration. Heterogeneity of SFTs affects imaging features on MRI and CT modalities. The biological behavior of soft tissue SFTs can not be predicted based solely either on histopathologic or imaging evaluation. Keywords: Solitary fibrous tumor, Magnetic resonance imaging, Soft tissue tumor, Computed tomography, Soft tissue tumor * Correspondence: email@example.com The Rizzoli Institute, via del Barbiano 1/10, 40136, Bologna, Italy © 2013 Papathanassiou et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Papathanassiou et al. Clinical Sarcoma Research 2013, 3:1 Page 2 of 8 http://www.clinicalsarcomaresearch.com/content/3/1/1 Introduction Solitary fibrous tumors (SFTs) are spindle cell neoplasms that most commonly occur in the pleura and represent less than 5% of all pleural tumors . In 1931, Klemperer and Rabin were the first to describe them as localized fi- brous mesotheliomas . Their histological origin has been controversial [3,4]. Pleural SFT is a well-established and generally benign entity with 7% -13% of cases being malignant at histopathological examination [5-7]. Even though SFTs are predominantly regarded as rare pleural neoplasms, a wide spectrum of extrathoracic sites has been reported, such as the head and neck regions [8-10], the abdomen, retroperitoneum and pelvis [11-17] and the soft tissues of the extremities [18-33]. Extrathoracic SFTs are rare and account for approximately 0, 6% of all soft tissue tumors [30-32]. Like their pleural counterparts, extrathoracic SFTs usually behave in a benign fashion but in approximately 10% of cases recur locally or metastasize [22,24]. So, an unusual tumor at an unusual location can be often poorly recognized affecting adversely the patient’s prognosis. Only few related studies predominantly with clinical and histopathological features have been reported (Table 1). Herein, we present, to the best of our know- ledge, the largest retrospective imaging review of 27 histologically-proven cases of SFTs in the soft tissues. Materials and methods From 1997 to 2009, twenty seven patients were diagnosed with soft tissue SFTs in our institution. Intra-abdominal or retroperitoneal SFTs were not included in this study Table 1 Review of the literature SERIES No of cases of soft tissue SFTS 1O’Connel JX et al. (1995) 1 2 Suster S et al. (1995) 2 3 Nielsen GP et al. (1997) 4 4 Mentzel T et al. (1997) 5 5 Vallat-Decouvelaere AV et al. 2 (1998)  6 Abe S et al. (1999) 1 7 Hasegawa T et al. (1999) 4 8 Harrigton P et al. (1999) 1 9 Krismann M et al. (2000) 1 10 Riss O et al. (2000) 1 11 Akisue T et al. (2003) 4 12 Rakheja D et al. (2004) 1 Figure 1 Unenhanced CT scan (A) displays a deep soft tissue mass 13 Anders JO et al. (2006) 1 with internal calcifications lying adjacent to the diaphysis of the left radius. The mass exhibits slightly lower attenuation compared to 14 Daigeler A et al. (2006) 4 the neighboring muscles (black arrow). On contrast CT scan (B), the mass 15 Martorell M et al. (2007) 1 is homogeneously enhanced (white arrow). Ultrasound (C) demonstrates a hypoechoic mass containing multiple calcifications. 16 Cranshaw IM et al. (2009) 13 Papathanassiou et al. Clinical Sarcoma Research 2013, 3:1 Page 3 of 8 http://www.clinicalsarcomaresearch.com/content/3/1/1 because Rizzoli Institute is a specialized orthopedic cen- These are old cases, with some dead patients. But the ter. Data concerning age, sex, physical examination, le- ethical committee approved it. Each patient entering into sion number, size and site was recorded. Assessment of the hospital agrees to allow the scientific use of their data. the available pre-operative imaging examinations was The study followed the rules of the ethical committee of performed and included plain radiography (X-ray), ultra- our institution. sound (U/S), digital substracted angiography (DSA), computed tomography (CT) and magnetic resonance im- Results aging (MRI). Two patients were examined with X-rays, This study group consisted of 17 female and 10 male CT scans and MR imaging and four underwent only patients (F/M: 1, 7) with a mean age of 50,3 years (range: CT scans and MR imaging. Three patients had X-rays and 19–82 years). All of the patients referred to our institution CT scans and six had only CT scans. One case was for management of palpable soft tissue masses of various investigated with X-rays and MR imaging and five had sizes. Focal swelling was present in 26 cases (96,2%) while only MR imaging. Two patients underwent U/S and pain occurred in 15 cases (55,5%) and the mean duration CT scans while two had U/S and MR imaging and another of symptoms was 13,8 months (range: 2–48 months). La- one had only U/S. Only one patient underwent CT scan boratory tests were unremarkable. Neither history of and DSA. All CT scans were performed before and after trauma nor infection was noted. The mean maximum contrast medium intravenous administration, except for diameter of the lesions was 8,7 cm (range: 3–18,8 cm). one case that didn’t have post contrast images. Dynamic Twenty lesions (74%) were located at the lower extrem- contrast medium infusion was carried out in one case ities with the thigh being the most frequent site (14/20) and enhanced CT scans were obtained at 30 s, 60 s, 90 s followed by the buttock (4/20), the calf (1/20) and the and 180 s after injection. MRI examinations obtained foot (1/20). Five lesions (18,5%) were affecting the upper from referring institutions as well included a variety of extremities, with the shoulder being the most common T1 weighted spin-echo (T1WSE), T2 weighted spin-echo location (4/5) followed by the forearm (1/5). Also, two (T2WSE), T2 weighted fast spin-echo with fat suppres- lesions (7,5%) involved the paravertebral area. All of the sion (T2 FSE Fat Sat), short T1 inversion recovery masses presented with round to oval shapes and well- (STIR) and T1WSE with fat suppression sequences (T1 defined margins. Twenty–five lesions (92,6%) were deep- SE Fat Sat). T1-weighted and Post gadolinium images seated (below and/or attached to inner surface of the fascia were not acquired in one and four cases respectively. lata or the antebrachial fascia) and two (7,4%) were superfi- Radiological evaluation included lesion size, location, and cial masses (attached to the skin or in the subcutaneous internal morphology along with CT density, MR signal in- area). Adjacent anatomic structures were mildly to mark- tensity and homogeneity, which were compared to neigh- edly displaced by the aforementioned lesions. boring muscles. Additionally, enhancement patterns, U/S Of the eighteen lesions imaged with CT scan, five were echogeneity and radio-opacity were recorded. All of the hypodense (Figure 1) and two were isodense (Figure 2A) lesions were surgically treated except for the most recent to adjacent musculature while eleven lesions appeared one. Histopathological analysis was based on macroscopic heterogeneous-mixed of iso and hypodense areas, on evaluation of the resected tumors, hematoxylin and eosin 1pre-contrast exams (Figures 3A, 4B). Attenuation values staining and immunohistochemistry (CD34, CD99, CD31, of the lesions were also higher than subcutaneous fat. S-100 protein, bcl-2, vimentin, EMA, desmin and muscle- Heterogeneous enhancement was evident in thirteen specific actin). lesions while homogeneous contrast uptake was observed Figure 2 Unenhanced CT (A) demonstrates a deep soft tissue mass in the left paravertebral area (asterisk). The mass is isodense compared to muscle. No bone erosion is observed. At 30 s post-contrast infusion (B) the lesion exhibits mild heterogeneous enhancement while at 90 s post-contrast infusion (C) the lesion shows more intense homogeneous and prolonged enhancement. Papathanassiou et al. Clinical Sarcoma Research 2013, 3:1 Page 4 of 8 http://www.clinicalsarcomaresearch.com/content/3/1/1 in four lesions (Figures 1B, 2C) (one case had no contrast administration). Septations were exhibited only in one CT case. All of the heterogeneously enhanced tumors contained markedly hyperdense portions admixed with patchy hypodense areas with mild to no enhancement (Figures 3B, 3C, 4C). In the dynamically –enhanced CT case, mild heterogeneous contrast uptake was depicted at 30 s and more intense prolonged enhancement was shown at 90 s and 180 s respectively (Figures 2B, 2C). A total of fourteen cases were examined with MR im- aging. On T1WSE, seven lesions were isointense to surrounding muscles (Figure 5A), one was hyperintense and five lesions were heterogeneous-mixed of iso and hypointense areas (Figure 3D). All lesions exhibited lower T1W signal intensity than subcutaneous fat. Of the nine tumors examined with T2WSE, seven lesions de- monstrated mixed intensities with hyper and hypointense areas (Figure 3E) and two lesions were hyperintense (Figure 5B). Nine lesions failed to suppress and presented with heterogeneous/mixed intensities on T2 FSE fat sat and STIR images. Post-gadolinium exams revealed homogeneous and heterogeneous enhancement in four (Figure 5C) and six cases (Figures 3F, 3G) respectively. Patchy unenhanced areas were evident in six out of ten enhanced cases while irregularly shaped areas of low to markedly high signal intensities were additionally observed on T2WSE images of the four cases that were not imaged with gadolinium. Septations were noticed in eight MRI exams (Figures 5B, 5C). In total, patchy areas with mild or no enhancement on CT and T1WSE images and areas of low to markedly high signal intensities on T2WSE were observed in 19 (70,3%) out of 27 cases. Ultrasound examination of five cases displayed three hypoechoic (Figure 1C) and two heterogeneous lesions of admixed hypo and slightly hyperechoic areas. Six available radiographs showed ill defined mildly radio- dense areas in the soft tissues with or without scattered in- ternal calcifications (Figure 4A). Gross calcifications were exhibited in six (22,2%) lesions. Additional file 1: Table S1–S3 display the imaging findings of the presented cases. Grossly, the resected masses were round or oval in shape Figure 3 Unenhanced CT scan (A) demonstrates a well-defined with well-defined margins. Cut surfaces were grayish-white heterogeneous deep soft tissue mass containing scattered to yellow (Figure 4D). Microscopically, tumors were hypodense areas (thin arrows). Enhanced CTimages (B–C) display made of haphazardly arranged spindle cells admixed heterogeneous enhancement. MR T1W image (D) displays an with collagenous tissue of variable vascularity (Figure 4E). isointense mass relative to adjacent muscle containing an area of relative lower intensity (white arrow) that has markedly high SI on The diffused network of capillaries, totally collapsed or wide T2W MR image (E) (black thick arrow). Heterogeneous enhancement open sinusoids, are surrounded by compact proliferation of is depicted on enhanced T1MR images (F–G). Central unenhanced cells with oval nuclei, distinct nuclear membrane, granular areas (asterisks) on both CT and MRI exams were of low SI on chromatin, small nucleolus, ill-defined cytoplasm, thick re- MRT1W images and high SI on T2W MR image. ticular fibers all around. The cells were organized in a co- called “patternless” pattern. There is no strict correlation between morphology and behaviour. However, histological aspects that could predict an aggressive and malignant be- haviour are: high cellularity, cellular atypia, extensive Papathanassiou et al. Clinical Sarcoma Research 2013, 3:1 Page 5 of 8 http://www.clinicalsarcomaresearch.com/content/3/1/1 Figure 4 (A) Radiograph demonstrates an ill defined and slightly radiodense area with multiple scattered calcifications of the right buttock (black arrow). (B) Unenhanced CT scan displays a deep soft tissue mass with internal calcifications. (C) The mass is nearly isodense relative to adjacent muscle and contains (mainly in its upper portion (black arrow)) an ill-defined hypodense area that remained nearly unenhanced on post-contrast CT images. Gross specimen (D): The lesion is roundish with polycyclic margins, greyish to yellow in colour, and firm in consistency. Histology (E): Proliferation of bland-appearing spindle cells in a patternless-pattern either in a storiform or haphazard pattern set in a collagen stroma (Hematoxiline & Eosine, 10x magnification). In some areas the cells are arranged around stag-horn haemangiopericytoma-like vessels (Inset, Hematoxiline & Eosine, 20x magnification). necrosis, >4 mitotic figures/10 HPF. Considering these Radiological findings concerned twenty seven well- aspects, aggressive features were present in 55,5% (15/27) defined masses with round or ovoid shapes displacing adja- of cases with necrosis in 22,2% (6/27) and degenerative cent anatomic structures. On unenhanced CT images, changes were shown in 7,4% (2/27) of cases. On pleural SFTs appeared isodense relative to muscle and some Immunohistochemistry, positive reaction was documented contained hypodense areas, while on enhanced CT images in 91,3% of cases for CD34, 60% of cases for CD99, 95,4% they usually exhibited mild to marked heterogeneous con- of cases for bcl-2 and 87,5% of cases for vimentin. trast uptake [35,36]. According to the Rosado-de- Christenson et al. study , isodensity on pre contrast CT Discussion scans correlates with hypercellular areas and capillary SFTs are rare neoplasms that usually involve the pleura networks while markedly enhanced regions represent or other serosal surfaces. Its origin has been controver- hypervascular areas, intermediate enhanced areas correlate sial. Previous experimental reports showed that sub- with hypocellularity, and patchy hypodensities correspond mesothelial cells had the ability to differentiate into to necrotic, myxoid or cystic changes. Of our eighteen mesothelial cells [34,35]. Despite they are frequently lesions imaged with CT scans, two were isodense, five regarded as pleural tumors, a variety of extrathoracic appeared relatively hypodense compared to neighboring locations has been reported like the meninges and the muscles and eleven were mixed of isodense and soft tissues of the neck [8-10], pelvis [11,16,17] and hypodense areas. On enhanced images thirteen lesions retroperitoneum [14,15], liver [12,13], and the soft tis- were markedly and heterogeneously enhanced including sue [18-33]. Soft tissue SFTs still represent a rare entity patchy unenhanced areas (Figures 3B, 3C, 4C) while only with 46 cases described in the English literature, mainly four exhibited a more homogeneous enhancement pattern from a histopathological point of view. They principally (Figures 1B, 2C). In reference to the dynamic char- affect adults between the fourth and seventh decades acteristics, Fuksbrumer et al.  and Moser et al.  of life [16,17]. Clinically, extrathoracic SFTs cause stressed the importance of marked and delayed enhance- symptoms that relate to tumor’ssizeand location. ment and washout in characterizing liver SFTs. In our Systemic symptoms such as hypoglycemia, arthralgia, study, one case (Figure 1B) that was assessed with dynamic osteoarthritis, and clubbing have also been reported. CT protocols, presented with mild arterial enhancement These symptoms usually subside upon tumor’sresec- and more intense and prolonged enhancement on late ven- tion . In our cases, apart from focal swelling and ous and delayed phases. These features related histolo- mild to marked displacement of neighboring anatomic gically to cellular areas (prolonged enhancement) admixed structures (e.g. muscles, neurovascular bundles), no with collagenous stroma (delayed enhancement). other regional or systemic symptoms occurred and la- According to the published MR features of SFTs, boratory analysis ranged within normal limits. isointensity to muscle is most commonly displayed on Papathanassiou et al. Clinical Sarcoma Research 2013, 3:1 Page 6 of 8 http://www.clinicalsarcomaresearch.com/content/3/1/1 intensity (Figure 3B, 3C). In most MR studies on mature fibrous tissue, the observed hypointensity on both T1 and T2-weighted sequences is related to the presence of hypocellularity and abundant collagenous stroma whereas fibrous tissue of relative increased cellularity and vascularity increases the signal intensity on T2-weighted sequences (Figure 5B) [34,37,38]. The aforementioned was noticed in all nine lesions that showed mixed to high sig- nal intensities on T2-weighted images. Gadolinium en- hancement of SFTs is generally a result of tumor vascularization that may vary from hypovascularity to hypervascularity. Of the ten cases that received gadolin- ium, six revealed intense heterogeneous enhancement and the remaining four cases were more homogeneously enhanced (Figure 5C). Similarly to the Tateishi et al. study , the enhancing portions corresponded histologically to areas of abundant cellularity combined with microvessels. Patchy heterogeneous areas of variable size were depicted in totally ten MRI exams (Figures 3F, 3G). Four of these cases demonstrated areas of low to intermedi- ate and markedly high signal intensity on T2WSE and the remaining six showed areas of mild to no uptake on post contrast images and were correlated to hypocellular collagenous stroma (n=10) with co-existing necrotic (n=3) or degenerative (n=2) changes. Hypocellular collagenous stroma was also correlated with the patchy unenhanced areas of the remaining nine (n=9) contrast CT cases with co-existing necrotic changes in only one case (n=1). On histologic analysis there were additionally two other cases with necrotic changes; one of which was imaged solely with MRI and appeared homogeneous both on pre and post gadolinium images and the other was imaged only with U/S and contained a few scattered hypoechoic areas. Moreover, thin hypointense on T2WSE, linear or curvi- linear structures were observed in eight out of fourteen MRI cases. These structures remained unenhanced and were attributed to smooth hypocellular fibrous septations. Figure 5 A deep soft tissue mass is intramuscularly located at Calcifications are suggestive of necrosis but they are only the right gluteus maximus muscle (white arrow). The mass is sporadically reported in extrathoracic SFTs . Likewise isointense relative to adjacent muscle on T1 MR images (A). The in this study, it was depicted in only six cases (22,2%). mass has high SI and contains septations on T2MR image (B: white The sonographic appearance of extremity SFTs is not arrowhead). On gadolinium –enhanced T1 images (C), the lesion displays marked homogeneous enhancement. Internal septations pathognomonic and in this series, generally comprised of remain unenhanced. a heterogeneous hypoechoic, well defined mass, with or without calcifications deeply located in the soft tissues. T1-weighted sequences along with an increase of signal Similarly, X-rays findings were not specific and mainly in- intensity on post gadolinium images and variable ap- clude that of a radio-dense soft tissue mass with ill defined pearance on T2-weighted sequences. It is considered margins and occasionally gross calcifications. In one le- that the variety of signal intensity on T2-weighted sion, DSA revealed marked vascularity of the lesion ori- images depends upon the different nature of the tumor ginating from the superficial and deep femoral vessels. components, namely, the amount of collagen and cellu- Histologically SFTs are well circumscribed and consist larity (fibroblasts), and on the presence of degeneration of a varying number of spindle cells randomly arranged in a collagenous background of variable vascularity. Some [9,34]. This series included seven masses of equal signal intensity on T1-weighted images relative to muscle cases present with a hemangiopericytoma-like pattern of (Figure 5A) and five lesions of heterogeneous-mixed irregular branching vessels and occasionally storiform or Papathanassiou et al. Clinical Sarcoma Research 2013, 3:1 Page 7 of 8 http://www.clinicalsarcomaresearch.com/content/3/1/1 herringbone patterns (Figure 4E) are seen . Immuno- Additional file histochemistry is essential in differentiating these tumors Additional file 1: Table S1. CT findings. Table S2. MR findings. Table from other spindle-cells neoplasms . Positivity for S3. US findings. CD34, CD99 and bcl-2 is an indicator of SFTs [3,16]. Pathological criteria for aggressiveness include tumor size Competing interests >5 cm, high cellularity, nuclear pleomorphism, high mi- The authors declare that they have no competing interests. totic rate (more than 4 mitosis in 10 HPF) and necrosis . In the present study 55,5% of cases (15/27) contained Authors’ contributions ZP made and wrote the article. MA and MG checked the histology. PP aggressive features; one tumor (max diameter: 5,2 cm) lo- checked the global scientific work. ES checked the surgical part. FG drafted cally recurred at 66 mo postoperatively, one case (max the manuscript. DV proposed the subject and checked the work. 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