Orbit, 2013; 32(6): 375–380 ! Informa Healthcare USA, Inc. ISSN: 0167-6830 print / 1744-5108 online DOI: 10.3109/01676830.2013.815222
C ASE REPORT
Correlation between Clinical Features, Imaging and Pathologic Findings in Recurrent Solitary Fibrous Tumor of the Orbit Gerardo F. Graue, Hermann D. Schubert, and Michael Kazim Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, New York, USA
ABSTRACT Purpose: To correlate clinical features, imaging and pathologic findings in recurrent Solitary Fibrous Tumor of the orbit (SFT) in order to predict long-term behavior. Methods: Clinical features, imaging and pathologic findings of three patients with biopsy proven SFT are reported. Demographic and clinical features were recorded at presentation and at each consultation; imaging was performed as a diagnostic tool and for follow-up. A biopsy was performed at presentation and subsequently when symptoms worsened. Pathology specimens were reviewed retrospectively to corroborate diagnosis. Intraoperative and histopathologic features were recorded. A correlation was made between clinical, imaging and pathologic results to identify outcome predictors of recurrence, locally aggressive behavior and malignant transformation. Results: All cases presented recurrent tumors with locally aggressive behavior over time. All were women in the fifth decade of life. Tumors induced proptosis, swelling of the lids and eye displacement at presentation and were diagnosed as other types of collagen-rich tumors before CD34 immunohistochemistry was available. Mean follow-up was 26.6 years (range 12–37). Relevant findings for all cases included a heterogeneous, irregular tumor containing cystoid spaces filled with mucoid material diffusely enhancing with imaging techniques. Intraoperative findings included a gelatinous matrix within the center of the tumor mass, which was not present at primary resection. Histopathology could not detect specific cellular patterns or immunological markers related to these changes. Conclusions: Recurrence and locally aggressive behavior was better predicted by imaging and surgical findings rather than histopathological characteristics. Cystoid degeneration in recurrent tumors may suggest malignant transformation over time.
Keywords: Malignant, prognosis, recurrent, solitary fibrous tumor
excision and close follow-up has been recommended. Adjuvant radio- and chemotherapy have not been shown to improve local control rates. Recurrences after incomplete resection are common and difficult to control.5 Its histological features and vascular pattern can overlap with several benign lesions such as leiomyoma, neurofibroma, fibrous histiocytoma and hemangiopericytoma which makes immunohistochemical evaluation mandatory for accurate diagnosis.6,7 A newly proposed SFT pathologic sub-classification scheme
Solitary Fibrous Tumor (SFT) is a mesenchymal neoplasia arising primarily in the pleura, though other systemic sites have been documented. The first description of orbital involvement was reported in 1994 by Westra et al. Since then, the orbit has been increasingly implicated as a primary site for SFT. Its unpredictable, non-histological related behavior and rare potential for metastasis have made therapeutic decisions challenging.1–4 When possible, complete
Received 11 January 2013; Revised 30 May 2013; Accepted 10 June 2013; Published online 1 August 2013 Correspondence: Gerardo Graue, MD, Edward S. Harkness Eye Institute, 635 W 165th St # 207, New York, New York 10032, USA. E-mail: [email protected]
376 G. F. Graue et al. distinguished 5 variants (fibrous, cellular, fat-forming, giant cell-rich variant and malignant SFT), and was felt to be predictive of clinical behavior.8 Furthermore, new immunohistochemical stains may also be of diagnostic value and predict the evolution of these tumors.6,9,10,11 We present three cases of recurrent SFT in the orbit and discuss long- term changes in clinicopathological, intraoperative and imaging characteristics.
MATERIALS AND METHODS Three patients treated at the Edward S. Harkness Eye Institute with an immunohistopathologically proven diagnosis of solitary fibrous tumor of the orbit were included. The charts, MRI, surgical reports and pathology specimens of the patients were reviewed. Histopathological examination included measures of cellularity, vascularity, necrosis, pleomorphism, hyperchromasia and mitotic rate. Immunohistochemical stains where performed for CD34, MIB1, p53, p16 and Ki67. Clinical and imaging (MRI) inspection was performed at each time point. Finally, a review of the existing literature on SFT was used to distinguish relevant features between our patients and those reported previously. This study adhered to the principles of the Declaration of Helsinki.
RESULTS Case 1 A 43-year-old female presented in June 1997 with a slowly growing mass in the superonasal quadrant of the right orbit producing moderate proptosis and inferior displacement of the right eye. On examination visual acuity was 20/25 in both eyes, Hertel exophthalmometry measured 17 mm OD and 15 mm OS, 2 mm of inferior displacement of the right globe was noted; no motility restrictions, pupillary afferent defect or color vision deficiency could be documented. Orbital surgery had been previously performed in 1979 to remove a mass in the same location that was interpreted by pathology as a well circumscribed, low mitotic activity spindle cell neoplasia compatible with leiomeioma of the orbit. Seven years later (March 2004) a spontaneous intralesional hemorrhage detected by MRI increased the grade of proptosis causing diplopia and an inferior right-sided scotoma identified by Humphrey automated visual field test. A repeat biopsy was performed 4 months later. Pathologic examination revealed a spindle cell neoplasia without significant mitotic activity positive
for CD 34 and vimentin, and negative to SMA, desmin, HHF-35, heavy caldesmon, S100 and CD31. A diagnosis of Solitary Fibrous Tumor matched these findings. In postoperative evaluation a metastatic survey was reported negative for systemic disease. She remained stable for 5 years until recurrence of a heterogeneous, irregular cystic tumor measuring 2.1 1 1.2 cm was noted on MRI (Figure 1A). Proptosis and diplopia progressed in the consecutive months until a lateral orbitotomy was performed in order to diminish symptoms and rule out malignant transformation. When the lesion was opened a dense, abundant viscous mucoid material presented. Pathological gross examination revealed multiple pieces of gelatinous tan to red soft tissue; on microscopic examination a spindle cell neoplasm positive for CD34, bcl-2 and vimentin and negative for SMA, S100, desmin and LANA with increased cellularity and mitotic activity was reported (compared to the lesions resected earlier). In follow-up consultation she remained stable but prognosis is uncertain at this point.
Case 2 A 67-year-old female was first seen on consultation in June 2006 complaining of diplopia, moderate decrease in visual acuity and proptosis of the right eye. Ophthalmic evaluation revealed deficiency in color vision and an afferent pupillary defect on the same eye. She had undergone a right lateral orbitotomy in 1973 for a posterior orbital mass. Pathologic analysis at that time showed a moderately to highly cellular neoplasm arranged in fascicles, intermingled with large amounts of collagenous tissue with cells featuring fairly uniform spindle or oval nuclei, supporting neurofibroma as the tissue diagnosis. Since then, she had noted slowly progressive proptosis and intermittent diplopia. Current MRI examination revealed an enhancing mass along the superior and posterior aspect of the right optic nerve sheath complex. A right fronto- and orbitozygomatic craniotomy was performed aiming to decrease proptosis, diplopia and optic nerve compression. Pathological examination of the excised mass revealed a moderately cellular neoplasm arranged in fascicles intermingled with large amounts of collagen. Neoplastic cells were fairly uniform featuring spindle shaped nuclei and inconspicuous nucleoli. Immunohistochemical staining strongly and diffusely expressed CD 34 and didn’t distinct EMA or S-100 resulting in a diagnosis of Solitary Fibrous Tumor. Findings remained stable until September 2009 when increased 2:1 mm proptosis, ocular motility Orbit
Correlation for Prognosis in Recurrent SFT of the Orbit
FIGURE 1. (A, B and C) Heterogeneous irregular tumor residua composed of cystoid spaces with diffuse enhancement on MRI revealed in several sections.
restrictions, diplopia on lateral gaze, decrease in visual acuity (20/50), afferent pupillary defect, deficiency on color vision and optic disc edema of the superior sector were documented. MRI examination showed an irregular, heterogeneous right orbital mass with cystic spaces, separated by septa, overlying the optic nerve and likely compressing it, involving the orbital apex, measuring 2.5 3 1.9 mm (Figure 1B). The mass showed diffuse and heterogeneous enhancement as well as inferior displacement of the lateral rectus. A stereotactically guided reopening and extension of the previous craniotomy with orbitozygomatic !
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osteotomy and extensive debulking of the tumor was performed in January 2010. Interestingly, abundant viscous mucous material was observed originating from inside the tumor. Pathologic gross examination revealed multiple pieces of tan to brown rubbery tissue. Microscopically, it was a spindle cell tumor without mitotic activity, demarcation or infiltrative features. Immunostaining of tumor cells revealed CD34þ, CD68-,bcl2þ,CD99þ, PR-, EMA-,S100P- and SMA –, consistent with Solitary Fibrous Tumor. On CT follow-up scanning a shell of collapsed tumor persisted in the superior and posterior orbit making prognosis uncertain.
378 G. F. Graue et al. TABLE 1. General characteristics found in patients with recurrent Solitary Fibrous Tumor of the orbit. Patient 1 2 3
Proptosis/ Dense, abundant Cell 4þMitosisþ CD34þVimentinþBcl-2þ diplopia mucoid material Vasc 3þ Proptosis/ Dense, abundant Cell 4þMitosis2þ CD34þVimentinþBcl-2þ diplopia mucoid material Vasc þ Lid swelling White tissue mildly Cell 4þMitosisþ CD34þVimentinþBcl-2þ Mild proptosis firm with mucoid Vasc3þ material
Previous diagnosis (year) FU (years) Leiomioma (1979)
cell = cellularity, FU = follow-up, NF = neurofibromatosis, SFT = solitary fibrous tumor, vasc = vascularity, þ = grade (out of þþþþ).
Case 3 A 50-year-old woman consulted in May 2000 with a one year history of left upper eyelid swelling. Painless, slowly progressive diplopia and visual decrease had been noted. On examination, superior lid ptosis with deep seated fullness in the central aspect of the superior left orbit was evident. On Hertel evaluation a difference of 2 mm (15–17) could be appreciated. CT examination reported a soft tissue mass in the central aspect of the left orbit without bone destruction, adjacent to the lachrymal gland. A transcutaneous biopsy was performed and histopathological analysis revealed a cellular spindle cell lesion with minimal nuclear pleomorphism without necrosis or significant mitotic activity. Immunological staining showed a CD34 and vimentin positive neoplasm. Smooth muscle actin, S100, cytokeratin, CD31, HMB45, HHF 35 and desmin were negative. These findings made the diagnosis of Solitary Fibrous Tumor. A metastatic survey found no systemic disease at that time. A slowly recurring mass was closely monitored by clinical and MRI examination over the next four years. By 2004 the lesion size had increased considerably. MRI examination (1.5 0.8 1.3 cm) and Hertel exophthalmometry gave a 2.5-mm difference (14–16.5) between both eyes: symptoms of lid swelling and eye discomfort also had increased. A second biopsy once more revealed a spindle shaped, highly cellular and vascular neoplasia with 1–2 mitotic figures per 10 high power fields without necrosis. In immunohistochemical analysis, CD 34 and vimentin were positive and desmin, HHF35, smooth muscle actin, S100, CD31 and cytokeratin were negative. The diagnosis of Solitary Fibrous Tumor was confirmed. During further follow-up, a left superior heterogeneous orbital mass with cystoid spaces and scar tissue continued to apparently involve the lachrymal fossa. Heterogeneous enhancement and a residual mass measuring 1.4 0.6 cm could still be seen by CT and MRI (Figure 1C), bone erosion or growths were absent. Visual acuity remained 20/20
OU without color vision deficiency and Hertel examination was still 16 and 17 mm, respectively. She was last seen on September 2012 with no significant clinical nor imaging change. A summary of relevant characteristics observed in all patients can be reviewed in Table 1.
DISCUSSION Extra pleural SFT arises more frequently in head and neck locations. The number of orbital SFT reported has increased in the last years, reaching an average of more than 5 tumors reported per year. With an overall 10–15% metastatic or recurrence rate (including lung, liver and bone as the most frequent sites) the WHO classification considers SFT of intermediate grade. As a consequence, a metastatic survey prior to complete surgical resection of functionally vital structures is recommended.1–7 In the newly proposed SFT designation by Kno¨sel et al. the metastatic rate was significantly higher for tumors in the cellular group (25%) than the fibrotic group (5%) or the other 3 groups with an overall survival rate of 85%.8 As reported by Vallat-Decouvelaere et al. features predictive of malignant clinical behavior in intrathoracic SFT can be equally applied to extra-thoracic SFT.12,13 Malignant features seen clinically in orbital SFT include diffusely invasive masses with rapid growth or recurrence, sessile forms and cystoid degeneration. Examples of malignant SFT in the orbit have been stated by few authors. Hayashi et al. reported a case of orbital SFT that extended to extradural middle cranial fossa and cavernous sinus.14,15 Carrera et al. described a case of orbital SFT with two local recurrences after surgical excision.16 Polito et al. informed of three cases of orbital SFT with aggressive osteolytic behavior and recurrence four years after the initial surgery.17 Recurrence and intrinsic tumor changes such as cystic degeneration (suggestive of malignant transformation) were found in every patient of this series
Correlation for Prognosis in Recurrent SFT of the Orbit
TABLE 2. General characteristics of malignant Solitary Fibrous Tumor. Clinical Diffuse/ Invasive mass Rapid growth/ recurrence Sessile mass
PDGF beta receptor 12q-15
Tran surgical gelatinous material
CD 34 dedifferentiation () MIB1
CD99, p53, p16,
Nuclear pleomorphism Hyperchromia
Heterogeneous irregular tumor residua filled with cystoid spaces with diffuse enhancement
Ki67 6.11% (6.11 1.05%)
High mitotic rates* (*) Defined as44 mitotic figures/10 high power, () Defined by sharp demarcation between areas of usual morphologically bland SFT and areas with poorly differentiated high grade morphology (11), (4) Increased expression, (5) Alterations and breakpoints, (1) Described by Graue, Schubert, Kazim.
although no evidence of histopathology transformation nor metastatic spread could be recorded. In this group, neither pathologic characteristic nor expression of inmunohistochemistry markers varied significantly from what was reported in the same patients’ previous biopsies and when reviewed. Considering that SFT has malignant potential even if not suggested by histopathological examination (such as gastric cancer) when found, recurrence and cystic degeneration should be considered relevant. By contrast, imaging techniques were useful to predict intrinsic minute tumor changes that differed from what is normally expected in collagen-rich fibroblastic tumors giving these techniques probably a special role for in assessing long term prognosis. (Table 2, Figure 1). Although it has not been previously established and requires additional investigation, symptomatic females in the fifth decade of life with previous resections and heterogeneous, irregular tumor residua filled with cystoid spaces (observed on MRI in contrast to the ‘‘classic’’ imaging characteristics18) could have an increased risk of malignant transformation over time and should be followed and managed aggressively. Solitary Fibrous Tumor of the orbit is a rare disease that still lacks useful prognostic factors, with this report we intend to contribute some potential markers. To be able to better predict long term behavior and malignant transformation, a multicentric cohort study is warranted.
DECLARATION OF INTEREST None of the authors has conflict of interest with the submission. The authors alone are responsible for the content and writing of the paper.
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