Solitary fibrous tumors in prostate: a case report with review of the literature

Abstract Background Solitary fibrous tumor (SFT) is a relatively rare type of mesenchymal neoplasm that occurs most frequently in the pleura. However, SFT originating from the prostate is particularly uncommon and only approximately 39 cases were reported before. Herein, we reported a rare case of a patient diagnosed with prostate SFT and presented a literature review. Case presentation: A 50-year-old Asian with irritative urinary symptoms was admitted to our hospital and almost all the evidence indicated that benign prostate hyperplasia (BPH) caused his symptoms. Therefore, transurethral resection of the prostate (TURP) was performed, but histopathological and Immunohistochemical (IHC) assessments showed that spindle cells arranged disorderly in the TURP specimen with a cluster of differentiation 34 (CD34), B-cell lymphoma-2 (Bcl-2), and signal transducer and activator of transcription 6 (STAT6) highly expressed and SFT was diagnosed. Finally, the patient underwent a radical prostatectomy and there was no disease progression observed thereafter. Conclusions Prostate SFT is extremely rare, and to our knowledge, this is the first case of prostate SFT that is difficult to differentiate from small volume BPH. IHC examinations are of great diagnostic value. Radical resection of the tumor appears to be the most effective method at present and continuous follow-up is highly recommended.


Introduction
A solitary fibrous tumor (SFT) is a rare spindle cell neoplasm of fibroblastic origin that was initially described by Wagner in 1870 [1], with a relatively indolent biological behavior [2]. SFT accounts for less than 2% of all soft tissue tumors and can arise in nearly all parts of the body, with 30% occurring in the pleura [3,4]. However, there were fewer cases of prostate SFT, with merely 39 cases presented in works of literature so far [5][6][7][8][9][10][11][12][13][14][15][16][17]. Therefore, scientists struggled to recognize its epidemiology, etiology, factors affecting prognosis, and the optimal therapeutic strategy [16]. Previously, the definitive diagnosis of prostate SFT could be extremely challenging to pathologists because of its overlapping histopathological and immunohistochemical (IHC) features with other spindle cell lesions in the prostate [18]. However, some scientists had revealed the pathogenesis of SFT and they found a strong relationship between SFT and NAB2-STAT6 fusion gene caused by recurrent intrachromosomal rearrangements on chromosome 12q13 and could be a critical point in reversing the situation of difficulty in diagnosis [19]. Currently, surgery is the first choice for this disease, and other treatments are not yet mature [20].
Here, we describe a case of a patient, with severe lower urinary tract symptoms (LUTs) and negative imaging findings, that was initially diagnosed as benign prostate hyperplasia (BPH) but subsequently as prostate SFT based on the biopsy of transurethral resection of the prostate (TURP) specimen. In addition, we conducted a comprehensive and careful literature review, including all previous case reports of prostate SFT. The purpose of this article is to offer assistance for the diagnosis and treatment of this tumor through our literature review and case presentation.

Case report
A 50-year-old Asian presented to our hospital, complaining of severe irritative LUTs and nocturia.
Interestingly, the patient went to a medical institution for the same complaint a month ago and transrectal ultrasonography (US) showed enlargement of prostate and bladder calculi. Moreover, his serum prostate-specific antigen (PSA) level was normal and his International Prostate Symptom Score (IPSS) was 21 (severe symptom range, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Thus, to relieve the severe symptoms of the patient, transurethral bladder lithotripsy was performed. However, the patient did not have any relief from his symptoms after the surgery, which lead to another hospital presentation. In our hospital, through digital rectal examination, we could find an enlarged prostate. US also showed enlargement of the prostate (46 mm � 35 mm � 28 mm) with uneven echo and no mass was detected. And residual urine was 60 ml. Maximum urinary flow rate (Q max ) was 6.3 ml/s (normal range, �15 ml/s). Therefore, his bladder outflow obstruction (BOO) was definite. Serum PSA level was normal (0.64 ng/ml; normal range, 0-4.0 ng/ml) while IPSS showed a severe symptom of 34 points. Accordingly, considering the patient's age, the hyperplasia of the prostate found in the auxiliary examination, and the BOO of the patient, we were preliminarily more inclined to diagnose the patient for the small volume BPH. Generally, a patient aged 50 should not have such severe LUTs, and small volume prostate could also hardly cause these severe symptoms based on our experience. So, we suggested that he perform a magnetic resonance imaging (MRI) examination, but he refused because of personal reasons. We speculated that perhaps financial reasons or psychological reasons arising from prolonged and severe symptoms contributed to his rejection of the MRI examination. Therefore, A TURP was undertaken, and the patient's symptoms were greatly relieved after the surgery. During the surgery, we also found that prostatic middle lobe and lateral lobe hyperplasia and did not find a high or tight bladder neck. Therefore, we were more convinced by our initial diagnosis of small volume BPH.
Nevertheless, a post-operative biopsy of TURP specimens revealed a large number of spindle cells (Figure 1), with IHC showing positive expression of cluster of differentiation 34 (CD34), B-cell lymphoma-2 (Bcl-2), and signal transducer and activator of transcription 6 (STAT6), which were typical manifestations of SFT (Figure 2). In addition, preoperative chest computed tomography (CT) showed that there was no mass in the patient's pleura, proving that the patient's SFT may originate from the prostate (Figure 3).
Considering immediate operative intervention was definitively difficult due to adhesions around the prostate caused by the TURP, we suggested the patient accept further surgery after 3 months. Consequently, the patient came to our institution 3 months later and the MRI did not show any tumors, and moreover, the whole body bone scan and the chest CT showed no metastasis ( Figure 4). We speculated the tumor probably was removed during the TURP or the tumor volume was too small to be detected by MRI. However, the patient told us that his nocturia frequency per day increased from 1 to 3 after surgery, and the very necessity of radical surgery on this tumor was indicated by the previous article. Therefore, after comprehensive analysis, we still advised the patient to accept radical surgical resection.
After the procedure, the post-operative biopsy showed an absence of residual tumor, so we rationalize that the patient's tumor may be removed during the TURP procedure ( Figure 5). Postoperative courses are uneventful, clinical and radiologic follow-up 3 months after surgery showed no recurrence and metastasis.

Discussion
SFT is a relatively rare mesenchymal tumor that was initially thought to occur only in the visceral pleura, but recently, still rare though, those out of the pleura are being increasingly disclosed [21]. Because of the scarcity of cases, a collection and documentation of existing literature are necessary. Therefore, we summarized the clinical symptoms, age of onset, tumor size, and other data of 39 previous cases of prostate SFT here and listed them (Table 1).
Previous works of literature suggested that the age of patients with prostate SFT varied widely, ranging from 21 to 87 years. However, only 4 patients were between the ages of 20 and 40, suggesting that this tumor may occur more frequently in the middle-aged and elderly. Detected by physical examination, 2 patients were with no symptoms and 4 patients had symptoms of haematuria, while the others all presented LUTs severely or lightly. Normal serum PSA level was detected in almost all the cases and tumor sizes ranged from 2 to 18 cm. Surgical resection was carried out ultimately in the majority of patients described in the previous works of literature and progression was not found in almost all of them during the follow-up period, indicating the effectiveness of the radical surgery.
The etiology of SFT still remains unknown, and some studies have shown that pleural SFT is not concerned with smoking or asbestos [1]. Due to the diversity of the location of this tumor, its clinical manifestations are also varied. Owing to slow growth and low metastasis risk, most pleural SFTs are generally asymptomatic. However, SFT located outside the pleura, especially in some special regions of the body, often leads to a series of clinical symptoms due to the neoplastic compression on adjacent tissues [20]. For example, a tumor in the meninges can cause    intracranial hypertension [22], a tumor that arises subcutaneously may form palpable masses, and a tumor in the prostate can lead to LUTs [20], as in this case. Interestingly, paraneoplastic hypoglycemia syndrome and paraneoplastic hypertrophic osteoarthropathy can be observed in some patients with SFT due to increased insulin-like growth factor 2 and hyaluronic acid produced by this tumor [23,24].
Macroscopically, the boundary of benign SFT is well-circumscribed from surrounding tissues, with a usually yellowish and firm cut surface. And irregular boundaries and areas of necrosis may be observed in the malignant and locally aggressive SFTs [25]. Histologically, Typical SFT displays the storiform distribution of spindle cells with areas of hyalinization, collagenization, and branching vessels [26]. The diagnosis of SFT eventually depends on histopathology and IHC rather than imaging findings which cannot distinguish prostate SFT from other prostatic lesions [27].
Histopathological and IHC characteristics of the tumor are diagnostically helpful to SFT and they are positive for CD34, CD99, and Bcl-2, but negative for cytokeratin (CK), smooth muscle actin (SMA), and other muscle markers (desmin, myoglobin, and myogenin) [28]. Nevertheless, diagnosis of prostate SFT was always a challenge for pathologists previously because of its significant IHC overlaps with other prostate spindle cell lesions (Table 2) [29]. With the development of new molecular technologies, the pathogenesis of SFT is gradually being unraveled by scientists, which may play a crucial role in diagnosing it. They found a strong relationship between SFT and NAB2-STAT6 fusion gene which is caused by recurrent intrachromosomal rearrangements on chromosome 12q13, and STAT6 IHC expression has been proved to be a highly sensitive and specific marker for SFT [30,31]. Moreover, recently, it was reported that aldehyde dehydrogenase 1 (ALDH1) was also over-expressed in SFT and therefore has been recommended as a supplementary diagnostic marker for this tumor [32]. The utilization of these newly discovered IHC expressions in these tumors, particularly STAT6, makes the diagnosis of SFT relatively less difficult [33].
In the present case, considering the age of the patient, the small volume of BPH showed by the transrectal US, severe LUTs, high IPSS, and normal PSA, which were common clinical manifestations of BPH [34,35], however, patients with PBNO also could also have severe LUTs, but the age of onset of PBNO should be earlier and about half of the patients with PBNO are presented with chronic pelvic pain [36][37][38]. In addition, imaging and physical examination also showed definite prostatic hyperplasia, so we did not make enough differential diagnoses with PBNO. What is more, during the operation, we can see prostatic middle lobe and lateral lobe hyperplasia, and no bladder neck stenosis was observed. After the TURP, the patient's LUTs were significantly relieved, which confirmed the diagnosis of small volume BPH. For small prostate SFT, which cannot be detected by image findings, the differential diagnosis from BPH can only be determined by histopathology and immunohistochemistry findings. Histologically, BPH is characterized by varying degrees of hyperplasia of glands, smooth muscle, and fibrous connective tissue [39], which can easily be distinguished from prostate SFT. Moreover, since the essence of BPH is actually hyperplasia of prostatic gland epitheliums and stromal cells while SFT is a type of mesenchymal tumor featured by a large number of spindle cells, the immunohistochemistry of BPH and SFT is also very different (Table 3).
Considering that benign SFT also has the likelihood of recurrence, complete tumor resection should be performed once the diagnosis of SFT is rendered [42]. And negative resection margin postoperatively is a powerful prognostic indicator of long-term survival while positive margins with no subsequent therapy account for up to 40% of locoregional recurrences and 75% of metastasis [20]. Moreover, this does not mean that surgery is the end to cure this disease. There was a previous report of recurrence and metastasis in patients with clear surgical margins [43], and tumors located in the meninges, pelvis, retroperitoneum, and mediastinum are more prone to these serious consequences [44]. Therefore, continuous follow-up is highly proposed for all patients with prostate SFT. Since SFT mostly recurs within 2 years after surgical resection according to some studies [1]. Patients should be advised to be followed with imaging examinations of the tumor-affected area for the first 2 years and yearly thereafter. In addition, studies have shown that although the probability of metastasis is not high, SFT located in the pelvic cavity is most likely to occur in metastasis of the lung and peritoneum [45]. Therefore, whether patients with prostate SFT need a continuous follow-up of the chest and abdominal imaging examinations is worthy of further discussion. For unresectable and metastatic SFT, surgery may not be the best option. Compared with conventional chemotherapy, Table 2. IHC characteristics of prostate spindle cell lesions [28].   recent studies have shown that antiangiogenic therapies, like sunitinib, pazopanib, and so on, have shown more promising effects on metastatic SFT. But more clinical trials are still needed to support and verify this approach [46]. There are several noteworthy points in this case. Firstly, the most common manifestations of BPH were LUTs, obvious prostate hyperplasia shown by imaging findings, normal serum PSA level, reduced urinary flow rate, and the presence of residual urine [35]. However, these findings may also occur in patients with prostate SFT. Thus, combined with its rarity, the possibility of small prostate SFT can be easily ignored with negative findings of US and digital rectal examinations. In this case, there was no positive US and digital rectal examination finding. Depending on the age of the patient and his small volume BPH, he should not be presented with such severe clinical symptoms in accordance with our clinical experience. These points should prompt the doctor to conduct deeper examinations of the patient. In addition, after searching the PubMed, Embase, and Web of Science databases, we found that this is the first case of prostate SFT that can hardly be differentiated from small volume BPH. Among all the reported cases of prostate SFT, no such small size of prostate and SFT has been reported before [10,14]. Secondly, when this patient was first admitted to our hospital, he rejected to perform an MRI examination due to personal reasons, and only transrectal US was initiated, which did not find his prostate tumor, probably indicating that US sometimes was not able to find small prostate tumor compared with MRI and other more accurate imaging examinations. Thirdly, in contrast with previous works of literature [9], we did not differentiate prostate SFT from prostate cancer, because this case did not have the characteristics associated with it. Patients with prostate cancer are often presented with elevated PSA and progressive dysuria, as well as progression and distant metastasis [47], which were not detected in this patient.

Conclusion
Prostate SFT is so rare in clinical practice that it is often difficult for clinicians to think of its existence, thereby threatening patients' lives. Clinically, if available evidence does not fully support the diagnosis of BPH, we should be alert to the possibility of small mesenchymal tumors. In accordance with our previous experience and literature review, we summarized a process of diagnosis and treatment of prostate SFT (Figure 6), which may provide assistance to the diagnosis and management of this uncommon tumor. Furthermore, IHC analysis is the most valuable diagnostic method for prostate SFT. Once diagnosed, radical prostatectomy is the most effective treatment to date and continuous follow-up is necessary because of its uncertain biological behavior.