Clinicopathological and genetic analysis of orbital solitary fibrous tumors

Abstract

Purpose

To investigate the clinicopathological and genetic characteristics of patients with orbital solitary fibrous tumor (SFT) for clinical reference.

Methods

This single-center retrospective case-series study assessed clinical manifestations, imaging features, treatment, and prognosis of patients with orbital SFT. Immunohistochemical staining and fusion gene detection were also performed.

Results

The mean age of monocular orbital SFT patients was 38.89 ± 19.69 years (10 males and 8 females). The most common complaint was unilateral proptosis (68%). Tumors were 2.47 ± 0.67 cm in diameter, primarily oval-like (72%), and located in the upper part of the orbit (82%). Immunohistochemical staining results are as follows: STAT6 + (100%), CD99 + (100%), GRIA2 + (100%), ALDH1 + (95%), CD34 + (86%), Bcl-2 + (62%), EMA + (57%), S-100 + (10%), SMA + (10%), CD31 + (0%), Desmin + (0%), P53 + ( 2–44%), Ki-67( 1–10%), VEGFR1 + (100%), VEGFR2 + (100%), VEGFR3 + (0%), PDGFRα + (90%), PDGFRβ + (100%). Among them, CD99 (95%), ALDH1 (90%), and CD34 (86%) were relatively high in moderate and strong positive expression. Bcl-2 staining score of the primary group was higher than that of the recurrent group, and the difference was statistically significant (P < 0.05). Bcl-2 staining score of the benign group was higher than that of the malignant group, and the difference was statistically significant (P < 0.05). Four NAB2-STAT6 fusion variants were detected in 21 paraffin samples, including 1 case each of NAB2ex4-STAT6ex2 and NAB2ex6-STAT6ex16 and 2 cases each of NAB2ex6-STAT6ex17 and NAB2ex7-STAT6ex4.

Conclusion

Orbital SFT were found in younger cohorts and smaller in size than other SFT. STAT6, CD99, GRIA2, ALDH1, CD34, and Bcl-2 are sensitive indications for orbital SFT, while CD99, ALDH1 and CD34 are more sensitive. High Bcl-2 expression is more common in primary and benign orbital SFT. The orbital SFT gene fusion variants include NAB2ex4-STAT6ex2, NAB2ex6-STAT6ex16, NAB2ex6-STAT6ex17, and NAB2ex7-STAT6ex4. An in-depth clinicopathological study can help explain orbital SFT.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12886-025-04223-4.

Introduction

Solitary fibrous tumor (SFT) is a spindle cell neoplasm of mesenchymal origin that can occur in various anatomical sites, with the pleura being the most common location (65%). The tumor was first described by Klemperer and Rabin in 1931 [1]. In contrast, orbital SFT is relatively rare, with the first reported case documented by Westra et al. in 1994 [2]. Although generally considered benign, SFTs can exhibit malignant potential, with a propensity for recurrence following incomplete resection and, in some cases, malignant transformation [3–6]. Consequently, accurate preoperative assessment, complete surgical excision, and standardized postoperative surveillance are critical for optimizing patient outcomes.

Due to the rarity of orbital SFT and the absence of expert consensus, its diagnosis and treatment remain challenging for clinicians. To improve ophthalmologists’ understanding of orbital SFT, we systematically analyzed the clinical characteristics, as well as the pathological, immunohistochemical, and genetic profiles of patients who underwent orbital tumor resection and received a definitive pathological diagnosis of SFT.

Material and methods

Participants and study design

This is a single-center retrospective study in which clinical and pathological data of patients diagnosed with orbital SFT were assessed. These patients presented in our hospital between September 2012 and March 2024. We used the patient's electronic medical records database to retrieve their clinical and demographic data. All data were collected and inputted into an electronic database by a specially assigned person. The research was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2024RN09) and performed under the principles of the Declaration of Helsinki. Written informed consent was obtained from the patients, parents, and guardians for participation in the study. For publication purposes, no identifying images or other personal or clinical details of participants are presented that compromise the anonymity of the participants in this study. However, consent was obtained to publish anonymized tissue images and information from the participants. The research design is illustrated in Fig. 1.

Fig. 1.

Research flowchart

Hematoxylin–eosin immunohistochemistry

Formalin-fixed paraffin-embedded (FFPE) samples were cut into 4-mm slides, deparaffinized in xylene, rehydrated with graded alcohols, subjected to hematoxylin–eosin (H&E), and immune-stained with the following antibodies: STAT6 (polyclonal rabbit, ZA-0647), CD99 (polyclonal mouse, ZM-0296), GRIA2 (polyclonal rabbit, 1:100, AF6307), ALDH1 (monoclonal mouse, 1:200, BF0220), CD34 (polyclonal mouse, ZM-0046), Bcl-2 (polyclonal rabbit, ZA-0536), EMA (polyclonal mouse, ZM-0095), S-100 (polyclonal mouse, ZM-0224), SMA (polyclonal mouse, ZM-0003), CD31 (polyclonal mouse, ZM-0044), Desmin (polyclonal rabbit, ZA-0610), P53 (polyclonal mouse, ZM-0408), Ki-67 (polyclonal mouse, ZM-0166), VEGFR1 (polyclonal rabbit, 1:100, AF6204), VEGFR2 (polyclonal rabbit, 1:100, AF6281), VEGFR3 (polyclonal rabbit, 1:100, AF4201), PDGFRα (polyclonal rabbit, 1:100, AF0241), and PDGFRβ (monoclonal mouse, 1:100, BF8138) were used in this study. Among these, the GRIA2, ALDH1, VEGFR1, VEGFR2, VEGFR3, PDGFRα, and PDGFRβ antibodies were obtained from Affinity Biosciences (USA), while all other antibodies, including their respective working solutions, were supplied by ZSGB-BIO (China). The staining intensity (0: negative staining, 1: mild staining, 2: moderate staining, 3: strong staining) and extent (0: < 1%, 1: 1—25%, 2: 26—50%, 3: 51–75%, 4: > 75%) were recorded for each case. The two scores were multiplied and graded as follows: 0: negative, 1–4: weak positive, 5–8: moderate positive, 9–12: strong positive [7]. The staining score differences of the above antibodies were compared according to the primary onset and recurrence, benign and malignant SFT, respectively.

RNA extraction and reverse transcription polymerase chain reaction (RT-PCR)

FFPE samples were analyzed for NAB2-STAT6 fusion variants using reverse transcription polymerase chain reaction (RT-PCR). Briefly, total RNA was extracted from FFPE samples using the RNeasy Mini Kit (Qiagen), following the manufacturer’s protocol. The first-strand cDNA was synthesized with 2-μg total RNA using the reverse transcription system (Promega). PCR was performed using Platinum Taq DNA polymerase (Invitrogen) in a final reaction volume of 25-μl containing 2-μl cDNA, and primers covered most of the fusion transcripts with various previously reported exon compositions [8–11]. The PCR products were separated on 2.0% agarose gels with ethidium bromide and visualized under UV illumination. PCR-amplified products were validated by Sanger sequencing to determine their breakpoints and exon compositions.

Statistical analysis

Data were analyzed using SPSS statistical software (IBM, USA. Version 27). Counting data are expressed as constituent ratios or percentages, such as gender, tumor location, and morphology. Shapiro–Wilk test was used for quantitative data to test normal distribution. Normally distributed data, including patient age and tumor diameter, was expressed as mean ± standard deviation (x̄ ± s). Data that did not conform to a normal distribution, such as disease duration, was presented as the median (P50). The Mann–Whitney U test was used to compare differences between primary and recurrent as well as benign and malignant groups. A p-value < 0.05 was considered statistically significant.

Results

A total of 18 patients were investigated in this study, including 10 males (56%) and 8 females (44%). Among these cases, Cases 2, 3, and 18 underwent two surgical procedures at our hospital due to tumor recurrence. Cases 5, 7, and 9 initially underwent surgery at other hospitals and were later treated at our hospital for recurrence. The average age was 38.89 ± 19.69 years (ranging from 2 to 73 years). All patients were monocular, with 11 left eyes and 7 right eyes. The median disease duration from the first assessment was 9 months. The most common complaint was unilateral proptosis (13/19,68%), and it could be accompanied by eye pain, eyelid swelling, a palpable mass, blurred vision, diplopia, tearing, or eye redness. Imaging examinations demonstrated that the mean tumor diameter of 16 available patients was 2.47 ± 0.67 cm, and the range was 1.5 cm to 3.5 cm. The tumors were oval in 13 cases, irregular in 2 cases, double oval, spindle, and nodular in 1 case each. Nine cases were primary in the extraconal space, 8 cases intraconal space, and 1 case had a tumor spanning the intraconal and extraconal space. Tumor location was upper outer, lower outer, upper inner, and lower inner quadrants in 7, 2, 7, and 1 patients respectively. Most tumors were in the orbit's upper half (14/17, 82%). Among 18 patients, follow-ups of 13 were successful, and 5 cases were lost. The follow-up time was 70.06 ± 42.97 months, ranging from 6 months to 11 years. Except for three patients who relapsed at 1, 69, and 117 months after the first surgery, no recurrence, distant metastasis, or death occurred in the remaining patients (Table 1).

Table 1.

Summary of clinical features of orbital SFT in the present series

Case no	Gender	Age (year)	Clinical History (month)	L/R	Quadrant	Shape	IN/OU	Size (cm)	Recurrence (month)
1	M	33	24	L	UO	Oval	OU	1.5	Lost to follow-up
2	F	2	2	R	UI	Oval	IN	3	1
3	F	60	3	L	UI	Oval	IN	2.2	69
4	F	29	12	L	UO	Double Oval	IN	1.8	NR
5	M	33	36	L	UO	Oval	IN	2.4	Lost to follow-up
6	F	30	0.67	L	UO	Oval	IN	2.2	NR
7	M	53	2	R	UI	Oval	OU	2.5	NR
8	M	22	1	R	UO	Oval	OU	3	NR
9	M	47	6	L	UO	Oval	OU	2.3	NR
10	F	73	36	L	UI	Oval	OU	3	Lost to follow-up
11	F	21	36	L	UI	Oval	OU	1.8	NR
12	F	32	1	R	UO	Oval	OU	2.2	NR
13	F	53	3	L	LI	Nodular	IN	2.1	NR
14	M	66	36	L	LO	Irregular	OU	4	Lost to follow-up
15	M	44	36	R	UI	Spindle	OU	-	NR
16	M	4	1	L	LO	Oval	OU	1.9	NR
17	M	43	12	R	-	Irregular	IN + OU	-	Lost to follow-up
18	M	55	36	R	UI	Oval	IN	3.5	117

M male, F female, L left orbit, R right orbit, IN intraconal, OU extraconal, UO upper outer, UI upper inner, LO lower outer, LI lower inner, NR No recurrence

- not available

The results of 18 available ultrasound findings are as follows: 5 patients had a hypoechoic mass, 4 had a middle-echoic mass, and 9 had a heterogeneous echogenic mass, in which 4 cases had tubular or patchy anechoic areas. In CDFI, the blood flow was graded by semi-quantitative method [12]: Grade 0 in 5 cases, Grade 1 in 1 case, Grade 2 in 5 cases, and Grade 3 in 7 cases, which means 5 cases with no blood flow signal in the mass, 1 case with little blood flow signal, 5 cases with moderate blood flow signal and 7 cases with abundant blood flow signal. The arterial blood flow spectrum was measured in 12 cases, and the arterial and venous blood flow spectrum was measured in 1 case. Among the 14 available CT results, we observed that most tumors showed soft tissue density shadows (11/14, 79%) with a clear boundary (12/14, 86%). And 1 case showed high-density shadow, and 2 cases had uneven density. The results of 5 available MRIs included four cases of isointense and 1 case of hypointense on T1WI. Two cases showed medium to low signal on T2WI, two showed high signal, and one showed heterogeneous signal.

A total of 21 tissue samples were obtained from 18 patients. On microscopic examination, SFTs were composed of spindled or ovoid cells arranged in a storiform or irregular manner, hypercellular areas and hypocellular areas alternated, associated with a background of collagen and characteristic thin-walled dilated blood vessels. In a few cases, giant cells can be seen in the interstitium. The diagnostic criteria of malignant SFT are hypercellularity, necrosis, nuclear atypia, and increased mitotic activity (≥ 4 mitoses/10 HPFs) (Fig. 2).

Fig. 2.

H&E staining results of SFT tissue (Benign: A, B, C; Malignant: D, E, F). A Tumor cells appear spindle-shaped or ovoid. The star indicates a dilated blood vessel. B The star highlights a fibrotic area within a hypocellular region. C Giant cell angiofibroma: The arrows indicate multinucleated giant cells surrounding blood vessels. D Diffuse necrotic area. E Presence of nuclear atypia. F The arrows mark mitotic figures. The left panels display images at low (4x) magnification (scale bar: 200 μm), while the right panels show high (20x) magnification views (scale bar: 40 μm)

Immunohistochemical staining results are as follows: STAT6 + (21/21, 100%), CD99 + (21/21, 100%), GRIA2 + (21/21, 100%), ALDH1 + (20/21, 95%), CD34 + (18/21, 86%), Bcl-2 + (13/21, 62%), EMA + (12/21, 57%), S-100 + (2/21, 10%), SMA + (2/21, 10%), CD31 + (0/21, 0%), Desmin + (0/21, 0%), P53 + (2–44%), Ki-67(1–10%), VEGFR1 + (21/21, 100%), VEGFR2 + (21/21, 100%), VEGFR3 + (0/21, 0%), PDGFRα + (19/21, 90%), PDGFRβ + (21/21, 100%). Among these antibodies, the proportions of moderate and strong positivity greater than 85% are CD99, ALDH1, and CD34, 95%, 90%, and 86%, respectively. The remaining antibodies all have proportions below 85% (Supplementary Table 1). Of all the indicators, only the Bcl-2 staining score in the primary group was higher than that in the recurrent group. The difference was statistically significant (P < 0.05). According to the benign and malignant groups, the Bcl-2 staining score in the benign group was higher than that in the malignant group, and the difference was statistically significant (P < 0.05). Other indicators had no statistical difference (Supplemental Table 2 and 3).

Using RT-PCR technology, we successfully detected four variants of NAB2-STAT6 fusion in 6 of 21 formalin-fixed and paraffin-embedded samples using the previously mentioned 8 pairs of primers. Among them, the fusion variant of case 18 was NAB2ex4-STAT6ex2, case 5 was NAB2ex6-STAT6ex16, cases 7 and 9 were NAB2ex6-STAT6ex17, and cases 2 and 8 were NAB2ex7-STAT6ex4 (Fig. 3).

Fig. 3.

NAB2-STAT6 fusion variants of orbital solitary fibrous tumors were identified by Sanger sequencing in this cohort. It reveals four different junction breakpoints in 6 successfully detected cases

Patients with the NAB2ex4-STAT6ex2 fusion variant were older and have a long disease duration and large tumor diameter, suggesting slow tumor growth. Compared with NAB2ex4-STAT6ex2, NAB2ex6-STAT6ex16/17 tended to have younger patients, shorter disease duration, and smaller tumor diameter. Compared with NAB2ex4-STAT6ex2 and NAB2ex6-STAT6ex16/17 fusion variants, the two patients with NAB2ex7-STAT6ex4 had a trend of youngest age, shortest disease duration and large tumor diameter, suggesting that the tumor proliferates rapidly in a short time (Table 2).

Table 2.

Clinical and immunohistochemical staining characteristics of different NAB2-STAT6 gene fusion variants

NAB2-STAT6 variant	Case no.	Gender	Age (year)	Clinical History (month)	L/R	Quadrant	Shape	IN/ OU	Size (cm)	P53	Ki-67
NAB2ex4- STAT6ex2	18	M	55	36	R	UI	Oval	IN	3.5	25%	3%
NAB2ex6- STAT6ex16	5	M	33	36	L	UO	Oval	IN	2.4	40%	1%
NAB2ex6-	7	M	53	2	R	UI	Oval	OU	2.5	2%	1%
STAT6ex17	9	M	47	6	L	UO	Oval	OU	2.3	35%	8%
NAB2ex7-	2	F	2	2	R	UI	Oval	IN	3	44%	3%
STAT6ex4	8	M	22	1	R	UO	Oval	OU	3	15%	2%

M male, F female, L left orbit, R right orbit, IN intraconus, OU outraconus, UO upper outer, UI upper inner

Discussion

SFT can present at any age but is most commonly diagnosed between 50–70 years [10], while the onset age of orbital SFT is relatively young [6]. The diameter of the tumor varies according to its location, with a median size of 5-10 cm [13, 14]. Some studies have found that compared with head and neck SFT, the size of abdominal SFT is larger, which may be related to the longer asymptomatic time, thus allowing the tumor to grow longer [10]. In this study, we observed that orbital SFT could occur in all ages (2 to 73 years), the age of diagnosis is mostly between 20 to 60 years (13/18, 72%), and the average tumor size is 2.47 ± 0.67 cm. It is observed that orbital SFT is characteristically much smaller in size and earlier in diagnosis than SFT elsewhere in the body because of its shallow location and small orbital volume. In terms of location, most tumors are located in the upper half of the orbit (14/17, 82%), which is consistent with the findings of Li et al. [15]. Therefore, SFT should be included in the differential diagnosis of tumors arising in the upper half of the orbit. The imaging results in this research lacks specific manifestations. Whereas the combination of hypervascularity (CDFI), well-defined CT margins, and variable MRI signals helps differentiate SFT from other orbital masses (e.g., cavernous hemangiomas or schwannomas).

Due to the diverse histopathological manifestations of SFT and the low sensitivity and specificity of immune markers, the diagnosis of SFT is more difficult. For example, CD34 is a glycoprotein on the cell membrane, which is not expressed in 5 to 10% SFT [16–18] but is expressed in other tumors such as Kaposi sarcoma and low-grade myofibroblastic sarcoma to varying degrees [19]. In 2013, some scholars found the existence of the NAB2-STAT6 fusion gene in SFT, which is considered a milestone in exploring the disease [8, 9]. Subsequent studies have also proved whether detecting that fusion gene, NAB2-STAT6 fusion protein or STAT6 protein, is a reliable method for diagnosing SFT [8–10, 20–23]. In a study covering 454 soft tissue tumors for the differential diagnosis of SFT, the positive expression of STAT6, CD99, GRIA2, ALDH1, CD34, and Bcl-2 in SFT were 100%, 41%, 64%, 76%, 88%, and 89%, respectively. Ouladan et al. concluded that the nuclear STAT6 and cytoplasmic ALDH1 expression are the most sensitive and specific markers in the differential diagnosis of SFT [23]. In this study, the positive rates of STAT6, CD99, GRIA2, ALDH1, CD34 and Bcl-2 are 100%, 100%, 100%, 95%, 86% and 62%, respectively. As for the positive grade, the above indicators' moderate and strong positive rates are 19%, 95%, 14%, 90%, 86%, and 24%. Therefore, CD99, ALDH1, and CD34 are relatively more sensitive. In previous studies, EMA, S-100, SMA, CD31, and Desmin were negative in most SFTs, and the results are consistent with this study [24].

Surgical resection is the primary approach for SFT treatment. Even if the tumor is completely removed, its recurrence, metastasis, and malignant transformation cannot be avoided. Given the efficacy of SFT to chemotherapy, which is still controversial, targeted biological agents are needed. Hatva et al. found the expression of VEGFR in meningeal SFT [25]. In a study that consisted of 26 SFT cases (17 cases of pleural, 9 cases of extrapleural), it was found that the positive expression rates of VEGFR1, VEGFR2, and VEGFR3 were 92%, 19%, and 31%, respectively [26]. Therefore, clinical research on VEGFR as a molecular therapeutic target has been conducted in succession. Currently, VEGFR inhibitors that can be used clinically include Pazopanib, Axitinib and Sunitinib. In a multicenter, single arm, phase II clinical study of Pazopanib enrolling 35 malignant and dedifferentiated SFT, the authors concluded that Pazopanib could be used as a systemic treatment for malignant SFT [27] and later, with the continuous enrollment of 31 advanced typical SFT patients, Martin-Broto and colleagues carried out another multicenter, single arm, phase II clinical study of Pazopanib in this cohort. The authors demonstrated that Pazopanib can be used as the first-line treatment of advanced typical SFT and seems to be more effective in advanced typical SFT than had already observed for malignant SFT [28]. An investigator-driven phase II study on Axitinib in advanced and progressive SFT showed that Axitinib is active in progressive advanced SFT and that it is important to switch antiangiogenic drugs at the time of SFT progression [29]. All the studies mentioned above are the application of antiangiogenics in systemic SFT, while the authors herein have not explored orbital SFT. However, given the active effect of antiangiogenics in systemic SFT and the high expression of VEGFR proved in this study, a postoperative combined application of antiangiogenics in case of subtotal resection of tumors in the orbit would be considered. Demicco et. al found that simultaneous overexpression of multiple growth factors is common in SFT, they enrolled 114 cases of SFT, the favorable rates of PDGFRα and PDGFRβ were 87% and 92%, respectively [26]. Pazopanib, Axitinib and Sunitinib, which are tyrosine kinase inhibitors, also target PDGFRα and PDGFRβ. In this study, the positive rates of PDGFRα and PDGFRβ were 90% and 100%, respectively. Therefore, the clinical value of the tyrosine kinase inhibitors mentioned above in orbital SFT is considerable, which still needs to be verified by prospective studies with large samples.

In the past, the prognosis of SFT was evaluated by mitosis and necrosis indicators in pathological examination. However, due to the limitation of histologic sections, they often cannot represent the general situation of the tumor, which is easy to lead to the misjudgment of tumor aggressiveness. At present, there is no accurate method to predict the aggressiveness of SFT by tumor or patient characteristics. Some scholars have proposed a new risk stratification scheme for SFT, which used patient age, tumor size, mitotic activity and tumor necrosis to predict the risk of metastasis [30]. However, given that the study only included 79 patients with non-meningeal SFT, its clinical value in evaluating the prognosis of orbital SFT remains to be verified. Some studies have pointed out that the genomic inversion of NAB2-STAT6 does not always occur at the same position. Several NAB2-STAT6 fusion variants have been found, including NAB2ex2/3/4/5/6/7-STAT6ex2/3/4/5/6/9/16/17/18/19/20 [8, 10, 20]. The influence of fusion variants on the clinical manifestations, histopathologic features and prognosis is inconclusive. A study evaluated a 52 SFT/HPC cohort by whole-exome sequencing and multiplex RT-PCR and identified 12 different NAB2-STAT6 fusion variants in 48 cases (92%). They found that tumors with the most common fusion variant, NAB2ex4- STAT6ex2/3, corresponded to classic pleuropulmonary SFT with diffuse fibrosis and mostly benign behavior and occurred in older patients (median age, 69 years). In contrast, tumors with the second most common fusion variant, NAB2ex6-STAT6ex16/17, were found in much younger patients (median age, 47 years) and represented typical HPC from deep soft tissue with a more aggressive phenotype and clinical behavior [10]. Another study also confirmed a similar conclusion involving 88 patients (28 intrathoracic, 37 extrathoracic, and 23 meningeal SFT). They concluded that compared with other variants, NAB2ex4–STAT6ex2/4 fusions were significantly predominant in the SFT characterized by intrathoracic location (P < 0.001), older age (P = 0.005), decreased mitoses (P = 0.0028), and multifocal or diffuse STAT6 staining (P = 0.013), but not found to correlate with disease-free survival [20]. Therefore, prospective multicenter studies with large sample sizes and long-term follow-ups will be needed to evaluate the prognosis of SFT from the perspective of fusion gene variants. In this research, we do find a tendency that patients with the NAB2ex4-STAT6ex2 fusion variant are older and have a long disease duration and large tumor diameter, suggesting slow tumor growth. Compared with NAB2ex4-STAT6ex2, NAB2ex6-STAT6ex16/17 tends to have younger patients, shorter disease duration, and smaller tumor diameter. These are consistent with the previous research. Compared with NAB2ex4-STAT6ex2 and NAB2ex6-STAT6ex16/17 fusion variants, the two patients with NAB2ex7-STAT6ex4 enrolled in this research had a trend of youngest age, shortest disease duration, and large tumor diameter, suggesting that the tumor proliferates rapidly in a short time. At present, there are few clinical studies on the characteristics of this fusion variant. We speculate that this variant may be more likely to occur in young patients, more likely to occur in the orbital position, and the tumor is larger and more aggressive.

The limitation of this study is that the number of orbital SFT cases included is small, and the type of study is retrospective analysis. However, given the rarity of orbital SFT, the existing literature is mostly case reports, and no expert consensus or guidelines have yet been formed. This article retrospectively analyzed the clinical manifestations, imaging, pathology, immunohistochemical staining, and genetic examination characteristics of orbital SFT patients in our hospital for over 10 years, which has specific clinical reference significance. Currently, the therapy of orbital SFT is in the exploratory investigation stage. In the future, we can gather information on individual cases to further our understanding of orbital SFT, including the discovery of fusion gene variants. Furthermore, potential tyrosine kinase inhibitors such as Pazopanib, Axitinib, and Sunitinib are viable options for treating recurring orbital SFT. Patients who are unable to undergo complete removal of the tumor may benefit from a combination of surgery, tyrosine kinase inhibitors, or local radiation to enhance the efficacy of orbital SFT treatment.

Conclusion

Orbital SFTs are more commonly found in younger cohorts and tend to be smaller in size compared to SFTs in other locations. They are predominantly located in the upper half of the orbit. STAT6, CD99, GRIA2, ALDH1, CD34, and Bcl-2 serve as reliable markers for orbital SFT diagnosis, with CD99, ALDH1, and CD34 demonstrating higher sensitivity. Notably, high Bcl-2 expression is more frequently observed in primary and benign orbital SFTs. Identified gene fusion variants in orbital SFTs include NAB2ex4-STAT6ex2, NAB2ex6-STAT6ex16, NAB2ex6-STAT6ex17, and NAB2ex7-STAT6ex4. A comprehensive clinicopathological study is essential for further understanding of orbital SFT.

Authors’ contributions

Conceptualization: T.L. Data curation: T.J and L.Z. Formal Analysis: L.Z and J.Z. Funding acquisition: T.L. Investigation: Q.W and X.L. Methodology: Q.W and X.L. Project administration: T.L. Resources: T.L. Software: Q.W and X.L. Supervision: T.L. Validation: T.L and E.E.P. Visualization: Q.W and X.L. Writing – original draft: Q.W and Z.N. Writing – review & editing: X.L, L.Z, E.E.P, T.J, L.Z, J.Z, and T.L. All authors reviewed the manuscript.

Funding

This study was funded by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-037A).

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to pariticipate

The research was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2024RN09) and performed under the principles of the Declaration of Helsinki. Written informed consent was obtained from the patients, parents and guardians for participation in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.