Recurrent dermatofibrosarcoma protuberans involving the lacrimal sac: A case report

Late recurrence of renal solitary fibrous tumour in the contralateral kidney

Patient: Female, 70-year-oldFinal Diagnosis: Solitary fibrous tumorSymptoms: Hypoglycemia • urinary retentionMedication: —Clinical Procedure: Surgical resectionSpecialty: Laboratory Diagnostics • Obstetrics and Gynecology • Pathology • SurgeryObjective:Rare diseaseBackground:Solitary fibrous tumors (SFT), rare soft-tissue neoplasms, are usually found in the thoracic cavity, and a uterine origin is extremely rare. SFTs with insulin-like growth factor-II (IGF-II) production induce non-islet cell tumor-induced hypoglycemia (NICTH), referred to as Doege-Potter syndrome.Case Report:A 70-year-old woman presented with urinary retention, and imaging revealed a huge mass occupying almost the entire pelvic space. She had a history of hysterectomy for leiomyoma of the uterus 7 years earlier. In her present course, she developed hypoglycemia, and NICTH was suspected. Her previous uterine specimen was reexamined, and immunohistochemistry (IHC) revealed the specimen to be CD34-positive and alpha-smooth muscle actin-negative, indicating that the uterine specimen was not leiomyoma but SFT. Therefore, the present pelvic tumor was considered to be a recurrence of SFT with NICTH, namely Doege-Potter syndrome. Surgical resection was performed, and the pathological examination showed the same histologic features as the previous uterine specimen, while IHC revealed the present specimen to be positive for CD34, signal transducers and activator of transcription 6, and IGF-II, consistent with the diagnosis of recurrent SFT with IGF-II production. The patient’s hypoglycemia improved after tumor resection. To confirm the IGF-II secretion from the SFT, we conducted immunoblotting of the patient’s perioperative serum, with results showing that the strong band of IGF-II in the preoperative serum disappeared after surgery.Conclusions:Because SFTs, especially those with Doege-Potter syndrome, often recur, sometimes with a very long interval, long-term cautious surveillance is required, even after complete tumor resection.

Metachronous Malignant Solitary Fibrous Tumor of Kidney: Case Report and Review of Literature

The authors report the youngest case of solitary fibrous tumor (SFT) with extensive involvement of the nasolacrimal duct system and discuss current literature regarding this tumor type. A 12-year-old female presented with a 6-month history of an enlarging right medial orbit mass. CT orbits revealed a well-circumscribed, enhancing lesion adjacent to the right nasolacrimal system. Pathology confirmed SFT (1.2 × 1.1 × 1.1 cm) with spindle cell morphology and a mitotic rate of 5 per 10 high power fields. Immunohistochemistry (IHC) was positive for CD-34 and signal transducer and activator of transcription 6 and negative for S-100, consistent with SFT. Next-generation sequencing confirmed NGFI-A-binding protein 2::signal transducer and activator of transcription 6 gene fusion. To the authors' knowledge, only 17 cases of SFT involving the lacrimal sac have been reported, of which, the average age was 43.5 years. Notably, SFTs with a high mitotic rate carry a heightened risk of malignant transformation. Given this patient's mitotic rate of 5 per 10 high power fields, positive surgical margins, and young age, close follow-up is imperative.

Solitary fibrous tumours (SFT) are fibroblastic mesenchymal tumours that can develop virtually at any site. It usually affects adults, and its incidence is estimated as 1 new case per million people per year. SFT is characterized by a gene fusion involving NAB2 (NGFI-A-binding protein 2) and STAT6 (signal transducer and activator of transcription 6); a higher nuclear STAT6 immunostaining can be seen in SFT cells, and it is considered an excellent marker for immunohistochemical diagnosis. The 2020 WHO classification defines two categories for SFT: intermediate (rarely metastasizing) and malignant. Many risk stratification models have been proposed to predict the behaviour of these tumour identities. In case of localized SFTs, the cornerstone of the treatment remains surgery with the aim of negative margins (R0) when technically feasible. In intermediate/high-risk SFTs with positive margins (R1/R2) with no possibility to re-resection or in meningeal high-risk SFTs, adjuvant radiotherapy (RT) could be performed. Neoadjuvant RT could also have a role in both extra-meningeal and meningeal localizations. Sole RT could have a role in managing non-resectable SFTs even in a curative intent. Medical therapy plays an important role in the metastatic/advanced SFTs. Conventional chemotherapy may be used, with doxorubicin and dacarbazine being active though yielding poor responses. Other active drugs with currently ongoing studies in SFT are eribulin and trabectedin. Antiangiogenetic treatments have also been shown to provide benefit in this histological subtype. An area of recent investigation is immunotherapy, with an ongoing randomized trial comparing nivolumab + ipilimumab versus pazopanib in advanced rare soft tissue sarcomas, including SFTs. Despite its rarity and therefore the difficulty in performing prospective randomized trials with a large number of patients, many promising results in perioperative (radiotherapy) or in the metastatic (medical therapy) setting have been obtained. This review overviews the main characteristics and provides the current knowledge on standard therapies.

Solitary fibrous tumors (SFT) are a rare type of mesenchymal-derived tumor not commonly found in the pediatric population, especially in the head and neck. Tumors of this nature are most commonly seen in the adult population and are identified with unique immunohistochemical markers, specifically signal transducer and activator of transcription 6 (STAT6) and hematopoietic progenitor cell antigen (CD34). Including SFTs in the differential diagnosis while working up a mass can be difficult considering their relatively non-descript appearance on imaging and the low yield immunohistochemical staining that must be ordered to confirm diagnosis. The current literature identifies only a handful of cases of SFTs occurring in the pediatric population, with a majority arising from the pleura. We present the case of a 13-year-old male who underwent radical excision of a left occipital triangle neck mass after radiological and pathological workup failed to conclusively make a diagnosis. Postoperative pathologic analysis revealed it to be an SFT. Due to the exceptionally rare presentation of SFTs in pediatric patients, the aim of this case report is to discuss diagnostic measures, solitary fibrous tumor etiology, as well as a recent risk stratification system used for the evaluation of postoperative disease progression. Our hope is that clinicians will include SFTs in their differential diagnosis when working up a neck mass in the pediatric population.

Solitary fibrous tumor (SFT) is an uncommon slow-growing mesenchymal neoplasm. It usually involves the visceral pleural and rarely has an intrapulmonary distribution. It is very sharp and round in shape when appearing intrapulmonarily. About 4% of SFT has hypoglycemia as a part of the paraneoplastic syndrome. We report a case of solitary pulmonary fibrous tumor with the presentation of hypoglycemia. After complete resection of the tumor, the blood sugar returned to normal range. Imaging pictures of the solitary pulmonary fibrous tumor and the mechanism of hypoglycemia caused by SFT are discussed.

Case Report: A 79-year-old man presented to our hospital with several months of right abdominal pain. CT reveled a large abdominal tumor (24 x 23 x 12 cm) involving the right hepatic lobe. HBV, HCV and HIV were all negative. Serum tumor markers, such as CEA, CA19-9, AFP, PIVKA-II, were all normal. Serum Interleukin-6 (IL-6) level elevated to 41.1 pg/mL (normal range: < 2.41). White blood cell count and differential leukocyte counts were all normal. No bacterial infection existed. Histologic examination revealed a spindle cell tumor with hyalinized change immunohistochemically stained for CD34, CD99, Bcl-2 and a negative staining against CD117 (c-kit), desmin, α-SMA, S100. Only 1% of Ki-67 positive stained area was observed. Immunohistochemical expression of IL-6 was clearly positive. A solitary fibrous tumor (SFT), arising from the retroperitoneum was diagnosed and a surgical resection was performed. This SFT partially invaded the right hepatic lobe and right kidney. The resected specimen showed a solid, encapsulated tumor with hemorrhage and weighed 4.0 kg. The tumor composed of “patternless” arrangement of spindle cells separated by dense bundles of collagen. Serum IL-6 level decreased to normal after a month of resection. Discussion: SFT is a very rare neoplasm that most frequently (80%) affects the pleura, but can also be found in many extrapleural sites (20%). SFT involving the liver is an extremely rare pathologic entity, predominantly affecting females and typically presenting in middle age. SFT is thought to have a low grade malignant potential with a slow cell proliferation. A surgical resection is thought to be a suitable therapy for SFT. However, the pathogenesis of SFT is still unclear. Furthermore, poor prognosis, such as tumor recurrences, despite of a surgical resection were reported in some cases. Interestingly, IL-6 staining in SFT was positive with a high level of serum IL-6 in our case. Immunohistochemical detection of IL-6 in SFT and elevation of serum IL-6, to our knowledge, have not been previously reported. Conclusion: The present case indicates some SFTs may contain high density of IL-6 inside and, therefore, serum IL-6 might be a useful biomarker related to progression of SFTs. Since SFT is a very rare tumor, the present case might be helpful to understand the pathogenesis of SFT. Further data accumulation, including IL-6 expression, is essential to establish the best therapeutic strategy for SFTs.

Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics

Solitary fibrous tumor (SFT) of the central nervous system is a rare spindle cell tumor of mesenchymal origin. The present study reports the case of a 44-year-old male patient with SFT. Magnetic resonance imaging demonstrated that the majority of the intracranial tumors exhibited uneven low signals on T1-weighted imaging (T1WI) and low mixed signals on T2WI, and there was an enhancement on enhanced scanning. Furthermore, the distal part of the left occipital lobe exhibited hypersignals on T1WI and T2WI, and this was significantly enhanced following enhanced scanning. The lower part of the scalp exhibited low signals on T1WI and high signals on T2WI, and there was no notable enhancement following enhanced scanning. Magnetic resonance spectroscopy demonstrated an elevated choline/creatine peak in the solid part of the tumor. Under the microscope, the tumor exhibited characteristic 'staghorn-shaped' blood vessels. As SFT is difficult to differentially diagnose via imaging, immunohistochemical analysis of CD34, vimentin and signal transducer and activator of transcription 6 was performed for the definitive diagnosis of SFT. Of note, surgical resection was the preferred treatment for SFT; however, due to the rarity of the tumor, subsequent adjuvant therapy and prognosis require further investigation.

Objective To investigate the clinical feature s of solitary fibrous tumor (SFT) in limbs and the optimal surgical approaches effect. Methods The clinical records of nine patients with SFT in limbs were retrospectively reviewed in department of orthopaedics of Sun Yat-sen Memorial Hospital between January 2005 and December 2016. There were three males and six females, with a median age of 44 years (15~55 years). Laboratory examinations showed normal results. MRI and biopsy were performed in all the cases. All the patients underwent surgical treatment with resection performed. The tumors originated from up libms in six patients, from lower limbs in three patients. Results All the tumors were totally excised. There was no postoperative mortality nor major complications. Among the nine patients, six patients had tumors in the upper extremities and three in the lower extremities. The primary clinical symptoms were painless masses, three of them with the distal limb numbness symptoms of compression. All the patients accepted MRI examinations to analyse their connections, confirm the borderline and size of the diseased tissues and its relation to the adjacent tissues. MRI examinations demonstrated that appearances of lesions were various. The expressions of vimentin(nine cases), CD348(eight cases), bcl-2(six cases), signal transducers and activators of transcription(STAT)-6(three cases) and Ki67(5% to 65%) were positive by immunohistochemical analysis. Conclusions MRI can be used to survey the tumor boundary of SFT, determine the adjacent relationship of SFT, provide the proofs for the diagnosis of SFT, and provide the basis for the selection of surgical procedures. Pathological immunohistochemistry is the main method for the diagnosis of solitary fibroma and can guide the formulation of adjuvant radiotherapy and chemotherapy after operation. Key words: Solitary fibrous tumors; Pathology; Radiography; Surgical treatment

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors commonly located in the pleura, soft tissues, or meninges and are characterized by the NGFI-A-binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion gene. Recent studies have indicated that nuclear STAT6 immunohistochemistry is a specific marker for SFTs. The authors reviewed fine-needle aspiration (FNA) specimens from extracranial SFTs diagnosed at their institution between 1993 and 2017. Histologic blocks and available formalin-fixed smears of FNA specimens from SFTs were investigated for STAT6 immunoreactivity using a monoclonal antibody. STAT6 immunocytochemistry was also investigated in schwannomas and spindle cell lipomas. Cytopathologic and clinical characteristics were described. Nineteen benign and 9 malignant SFTs were identified. Both benign and malignant SFTs had a female predominance (female-to-male ratio, 2.8:1 and 1.25, respectively). Localization varied, and approximately one-half of the extrapleural tumors were located in the extremities and frequently were intramuscular. Benign and malignant primary tumors had limited differences in cytologic presentation, the most notable feature being nuclear pleomorphism. Cytomorphologic features included low-to-moderate cellularity of mixed oval, elongated, round, and stellate cells with pink collagenous stroma and hypercellular clusters with infrequent atypia. In metastatic SFTs, the cytopathology was suggestive of sarcoma. Immunohistochemistry revealed nuclear STAT6 immunoreactivity in SFTs (n = 5) with cytoplasmic reactivity in cytologic mimickers. Benign and malignant SFTs have common cytopathologic features, and the ability to distinguish between them is limited. Nuclear STAT6 immunoreactivity is a valuable cytologic marker for SFTs. Cancer Cytopathol 2018;126:36-43. © 2017 American Cancer Society.

This 49-year-old woman with a 1-year history of deteriorating quadriparesis visited our clinic in November 1999. She required a cane to walk and presented with a large elastic mass in the neck posteriorly. Neurological examination showed exaggerated deep tendon reflexes in the upper and lower extremities bilaterally as well as positive Hoffmann and Babinski reflexes bilaterally. Sensory disturbance and diffuse muscle weakness (Grades 2/5 on the right side and 4/5 on the left) below C-5 were also present. Magnetic resonance (MR) imaging revealed an 8� 5 � 8–cm extradural tumor (Fig. 1). Angiography demonstrated an intense hypervascular tumor fed by the bilateral ascending cervical and vertebral arteries. Following embolization, we resected the tumor, first separating the posterior extraspinal portion of the tumor in the muscular layer from surrounding tissues and excising it at the surface of the laminae, where severe bleeding was encountered. After hemostasis, we conducted a C2–5 laminectomy, and completely removed the tumor. The bilateral facet joints remained intact during laminectomy, making fusion unnecessary. The tumor had a gray pseudocapsule and was easily separated from the dura mater. Histological examination was compatible with a solitary fibrous tumor (Fig. 2). At 1-year follow-up examination, the patient suffered no neck pain or neurological deficits except for slightly exaggerated lower-extremity deep tendon reflexes. Radiography revealed no cervical instability or malalignment. No residual or recurrent tumor was found on MR imaging. Solitary fibrous tumors were first differentiated from diffuse mesothelioma by Klemperer and Rabin.4 These lesions are most commonly found in the visceral pleura but are considered to arise from mesenchymal rather than mesothelial tissue. Those occurring in the spinal canal are so rare that only 12 cases have been reported to date. 1–3,5,6 Of these, four harbored tumors in the cervical and thoracic spine and three in the lumbar spine. On the axial plane, tumors were intradural–extramedullary in seven, extradural in four, and intramedullary in one. Diagnosis of solitary fibrous tumors is based on characteristic pathological findings. Because CD34 staining, however, is also positive in other tumors such as hemangioma, fibroma, and epithelioma, the final diagnosis should be made on the basis of hematoxylin and eosin and CD34 staining together. Solitary fibrous tumors of the spine are usually benign, and marginal resection is considered to be sufficient. One case in which the tumor recurred after partial resection has been reported, indicating that complete resection and careful follow-up examination are mandatory. 2

Objective: To study the clinicopathologic features, the differential diagnosis and the expression of STAT6 in solitary fibrous tumor (SFT). Methods: Eighty cases of SFT were evaluated. The expression of STAT6, CD34, CD99 and bcl-2 protein was studied in these cases and in other groups of soft tissue tumors by immunohistochemical EnVision method. The results were analyzed and relevant literature were reviewed. Results: The expression rate of STAT6 in SFT was 97.5% (78/80) and that in other soft tissue tumors was 3.3% (3/90). The difference was significant (P<0.05). The expression rates of CD34, CD99 and bcl-2 were 88.8% (71/80), 76.3% (61/80) and 75.0% (60/80) in SFT, respectively, which were significantly different from STAT6 expression rate (P<0.05). Conclusions: The expression of STAT6 in SFT has high sensitivity (97.5%) and specificity (96.7%). The expression of STAT6 in SFT is higher than that of CD34, CD99 and bcl-2. STAT6 may be a useful marker for clinical diagnosis of SFT.

Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calculated using the Demicco risk stratification system (RSS). The results were combined and examined to assess the accuracy of risk stratification and classification. The most common location was in non-extremities; 66% were located in soft tissue or subcutaneous areas and 92.8% in deep locations. On microscopic analysis, 38.1% of tumors revealed hypercellularity with a predominant patternless and/or hemangiopericytic growth pattern; 13.4% had ≥4 mitoses/10HPF; 16.5% showed necrosis, and almost half the tumors showed at least focal myxoid areas. Dedifferentiation was observed in three tumors. Immunomarker expression in SFTs was as follows: CD34 92.9%, CD99 57.1%, Bcl2 67.9%, neuroendocrine markers (at least 1) 25.7%, Desmin 14.3%, CK(AE1/AE3) 3%, Apoptotic Protease Activating Factor (APAF-1) 87% and finally Ki-67 ≥ 10% in 14.4%. The NAB2/STAT6 gene fusion was detected in 50 tumors. After a median follow-up of 90 months, 9.3% recurred, 11.3% metastasized, 10.3% died of disease and 76.2% were free of disease. TERT mutations were detected in 40.6% of the SFTs; the TP53 mutation was detected in 17%, and only 9.3% showed both mutations. According to the Demicco RSS, 6.1%, 11.3% and 82.4% of the tumors were classified as high, intermediate or low-risk of metastasis, respectively. All high-risk tumors had ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10, HTER and/or TP53 mutation and poor evolution. The intermediate risk SFTs with worse evolution displayed the HTER mutation. Almost all low-risk tumors had a favorable evolution, although four showed at least one adverse factor (Ki-67 ≥ 10, ≥4 mitoses/10HPF or high tumor size) and had a worse evolution. An integration of clinical, morphologic, immunohistochemical and molecular findings may improve risk stratification and classification and better predict patient outcome. The unfavorable course seems to be more frequent in high-risk SFTs, although it is not exceptional in low-risk SFTs either; hence, a long-term follow-up is required independently of the assigned risk stratification score. The inclusion of molecular findings in risk stratification systems could improve the precision in the classification of SFTs, especially those of intermediate risk. Future studies will be required to determine the most effective way to incorporate molecular analyses into RSS on SFTs. The coexistence of several adverse factors such as ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10%, mutations in HTER and/or p53 may suggest a closer clinical follow-up regardless of the histological appearance of the tumor.