SFT is an anatomically ubiquitous mesenchymal neoplasm with an equal gender distribution that often presents as a large, deep-seated soft tissue or visceral mass. It may occur in various extrapleural sites, such as respiratory tract, nose and paranasal sinuses, parotid gland and salivary gland, thyroid, lung, etc [2, 3]. However, since this disease is rare, few cases (within 100) with orbital SFT have been reported, especially recurrent orbital SFT.
In the present research, clinical, imaging, and pathological features of 3 patients with recurrent orbital SFT were retrospectively compared. We also used the PubMed database to search for recurrent orbital SFT, and 21 related literatures were selected to explore their clinical and pathological features [3, 4, 6–23]. To our knowledge, the current study involved the majority of previous researches on recurrent orbital SFT published in English in the recent two decades.
SFT was originally thought to occur exclusively in the intrathoracic region, while it has been recently described in extrapleural sites (e.g., orbit). SFT of the orbit is a rare lesion, which can be misdiagnosed as hemangioendothelioma, fibrous histiocytoma, meningioma, or neurofibroma. Its main clinical manifestations are painless protrusion of the eyeball, ptosis, diplopia, and limited eye movement. Painless, non-pulsating, incompressible masses can be touched by physical examination . The patients involved in the current study had a mean age of 54 years old, and their clinical manifestations included exophthalmos, ptosis, abnormal eye position, and blurred vision, which were consistent with those reported previously [24–27].
Recurrence time was also counted through literature analysis and the current cases (see Table 1), although the duration of recurrence after the first surgery for patients who aged ≤ 50 and ༞50 years old showed no significant difference (P = 0.19). The average time to recurrence in patients who aged under 50 years old was shorter than that in those who aged over 50 years old, suggesting that young patients were more likely subjected to recurrent orbital SFT. Moreover, 21.2% of patients with SFT had multiple recurrences, including Case #3 presented herein and those reported previously. A number of scholars have shown that the failure of radical resection is a high risk-factor for tumor recurrence . The tumors of 3 patients reported in the current study were located in the posterior muscular cone of eyeball, which caused difficulty in their surgical removal. After reviewing the literatures, we found that orbital SFT can originate from any part of the orbit, mainly from the superomedial orbital quadrant (20%), medial orbit (15%), and superotemporal area (13%). Lacrimal sac area and inferotemporal area also account for 9.5% and 7%, respectively [3, 28]. However, after comparing the clinical characteristics of the previously conducted researches and the cases herein presented (Table 1.), the most common site for recurrent orbital SFT was the retrobulbar area of the orbit (23.8%). This site is the most difficult area of orbital surgery, and the surgical approach, surgical method and surgical field exposure may all affect the prognosis . The fact that the tumor was in almost the same place before and after recurrence suggested that the failure of the first surgery to completely remove the tumor, which left residual tumor, could be responsible for the recurrence. In addition to the local recurrence, orbital SFT is also associated with distant metastasis. In the present research, among the 4 cases, only Case #3 had a history of multiple recurrences. As distant metastases scarcely occur, further study needs to be conducted.
The MRI findings of orbital SFT showed that lesions had equal density with the gray matter on T1WI, and values of signal intensity on T2WIs were controversial [30–33]. Previous studies reported that orbital SFT is rich in fibrous matrix and T2WI should be dominated by a low signal intensity, however, in several reported cases of malignant orbital SFT, cystic degeneration could be detected with a high signal intensity, suggesting that cystic degeneration could be related to malignant transformation [4, 34]. In addition, the contrast-enhanced MRI showed enhanced SFT, while the enhancement can be uniform or uneven, and it may be associated with the distribution of blood vessels and capillary permeability [35–37]. In the current research, 2 patients underwent MRI of the orbit, and the values of signal intensity on T1WI and T2WI before and after the recurrence of SFT were consistent, indicating that MRI signals did not significantly change before and after recurrence. Changes in cystic lesion were both observed before and after recurrence in Case #2. According to the results of IHC, the patient was diagnosed as benign orbital SFT before recurrence and malignant SFT after recurrence, demonstrating that change in cystic lesion may not be the specific marker for differentiating benign SFT from malignant SFT.
Orbital SFTs are largely benign tumors with few instances of recurrence. Grossly, they could be round- or long oval-shaped specimens. The masses of three cases in the current study were elliptical, all of which were behind the eyeball and confined by the orbital wall. Yang et al pointed out that although a tumor is mainly benign, it may involve the orbital bone and occasionally penetrate the orbital wall and invade the intracranial structure . During the second surgery on Case #1 and Case #2, surgeons found an adhesion between the masses and the orbital bone. In Case #3, the tumor not only involved the right-sided orbit, but also maxillary sinus, ethmoid sinus, and frontal sinus. However, after recurrence, the tumor may inevitably adhere to the bone wall due to the previous surgery, thus, destruction of the tumor on orbital bony fissure before and after recurrence still needs further observation and verification.
In the review of subjects of previous studies, it was found that SFTs shared a histopathologic morphology, which was recognized for spindle cells, remarkably characteristic ‘staghorn’ blood vessels, and matrix with numbers of collagen bundles . The results of IHC showed that CD34 is a useful marker in the diagnosis of SFT. Previous studies reported that SFT expressed CD34 in 90% of cases, CD99 in 70% of cases, and Bcl-2 in only 30% of cases [26, 37]. In 2016, the World Health Organization (WHO) classified tumors with a classic SFT phenotype as grade I, tumors with intermediate or HPC phenotype as grade II, and tumors with five or more mitoses (× 10 HPFs) as grade III . A number of scholars demonstrated that the presence of mitosis is a poor prognostic indicator, and, Sagiv et al. emphasized that the number of mitotic figures higher than 4/10 HPFs can be a predictor of malignant SFT . In addition, nuclear atypia, cell proliferation, and necrosis were also considered as manifestations of malignant SFT . It has been reported that the percentage of Ki-67-positive cells tends to increase correspondingly in SFT with an invasive tendency, which is clinically significant for the selection of postoperative treatment plan and assessment of tumor prognosis [37, 39–41]. In three cases reported herein, tumor cells were spindle-shaped and densely distributed in collagen fibers. The nuclei were oval, round or spindle-shaped, the cytoplasm was pale and eosinophilic, and branched or antlers-shaped blood vessels could be observed. IHC showed CD34 positive, while S-100 and CK negative, which were consistent with the diagnosis of orbital SFT. In cases #1 and #2, nuclear abnormalities were found for the first time after recurrence, and those cases were diagnosed as malignant SFT with mitotic activity of ≥ 4/10 HPFs. To date, few reports have concentrated on the recurrent orbital SFT, and there is currently no large sample-sized controlled trial related to the pathological manifestations of recurrent orbital SFT before and after recurrence. In the present study, we compared the pathological manifestations of 24 orbital SFT patients before and after recurrence, including tumor necrosis, mitotic rate, and the percentage of Ki-67-positive cells. As shown in Table 2, the rate of SFT mitosis was elevated in the relapsed eyes, and the proportion of Ki-67 positive cells remained stable in some cases, while it increased in a large proportion after recurrence, indicating that recurrent orbital SFTs tend to increase in malignancy in terms of both morphological features and IHC results. In addition, the pathology testing of Case #3 after repeated recurrences revealed new occurred necrosis, and the percentage of Ki-67-positive cells was about 50%, suggesting that the degree of malignancy may be higher after several recurrences, while the above mentioned results should be verified by further case-control studies with a larger sample size.
In conclusion, the time to recurrence of orbital SFT in the reported patients ranged from 3 months to 20 years, and the average time to recurrence in patients who aged under 50 years old was shorter than that in those who aged over 50 years old. In the current report, 2 patients underwent MRI of the orbit, and the values of signal intensity on T1WI and T2WI before and after recurrence of SFT were consistent, indicating that MRI signals did not significantly change before and after recurrence. Morphological features and IHC results indicated that recurrent orbital SFTs tend to be malignant. The degree of malignancy may increase with the frequency of recurrence. Therefore, orbital SFT requires radical resection to avoid tumor recurrence and change of malignant tendency.