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| Malignant Recurrent Orbital Solitary Fibrous Tumor |
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Jaydeep N Pol1, Dipti B Patil2, Sharad S Desai3, Adnan B Calcuttawala4
1 Department of Pathology, Mahatma Gandhi Cancer Hospital, Miraj, Maharashtra, India
2 Department of Maxillofacial Surgery, Mahatma Gandhi Cancer Hospital, Miraj, Maharashtra, India
3 Department of Oncosurgery, Mahatma Gandhi Cancer Hospital, Miraj, Maharashtra, India
4 Department of Radiation Oncology, Mahatma Gandhi Cancer Hospital, Miraj, Maharashtra, India
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| Date of Submission | 13-Jul-2021 |
| Date of Decision | 18-Mar-2023 |
| Date of Acceptance | 03-Apr-2023 |
| Date of Web Publication | 11-May-2023 |
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 Abstract | | |
Solitary fibrous tumor (SFT) is a rare mesenchymal tumor of fibroblastic origin commonly occurring in pleura. It can occur at many extrapleural sites but is rare in orbit. Most cases are benign and recurrence is not unusual in the head and neck and orbit and is usually due to incomplete surgical excision. However, malignant transformation (MT) in orbital SFT is extremely unusual. We present a case of orbital SFT in adult male who developed recurrence with MT eight years after initial surgical excision. He underwent left orbital exenteration. The recurrent tumor revealed features of malignancy with areas exhibiting morphology typical of SFT. The immunochemistry confirmed the diagnosis of SFT with MT. The patient was given adjuvant radiation and was disease free for the last 18 months. Identification of malignancy in orbital SFT is important for the patient to receive appropriate postoperative treatment, as seen in the present case.
Keywords: Malignant, orbital, recurrent, solitary fibrous tumor
| Introduction | |  |
Solitary fibrous tumor (SFT) is an uncommon neoplasm of fibroblastic origin that prototypically arises in the pleura.[1] The tumor has been reported at various extrathoracic sites and rarely involves the head and neck region.[2] Orbital involvement is rare and approximately only 150 cases of orbital SFT (OSFT) have been reported in the literature so far.[3] Majority of them are benign, although up to 12%–22% may be malignant.[4] Although recurrence is not uncommon (30%–37%) in OSFT, malignant transformation (MT) is extremely rare.[3] Here, we present a case of OSFT who developed recurrence with MT after a gap of eight years of initial surgery.
| Case Report | | |
A 57-year-old male presented with complaints of gradually increasing painless swelling in the left eye since six months and loss of vision for three months. On examination, the left eyeball showed severe proptosis with lagophthalmos and lateral dystopia. A non-pulsatile, non-tender mass was seen in the medial quadrant of the orbit extending to the superior quadrant [Figure 1]a. The left eye had gross mobility restriction in all directions. The right eye was normal. The patient gave history of surgery eight years back for left orbital proptosis which was diagnosed as OSFT. After the first surgery, he was asymptomatic with a good vision and good eyeball mobility in all directions. After disease-free interval of eight years, he developed a progressive elastic hard, non-tender left orbital mass. His routine laboratory investigations were normal. | Figure 1: (a) Clinical image showing proptosis with lagophthalmos of left eye, (b) and (c) CT images showing a retrobulbar mass in the left orbit, and (d) gross image showing a retrobulbar fleshy brown tumor with an uninvolved eyeball
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His contrast-enhanced CT scan showed a retrobulbar mass in the left orbit involving both extra- and intraconal compartments inseparable from optic nerve and extraocular muscles. There was a mass effect causing bony expansion of the orbital walls with thinning and fenestration. Through these fenestrations, it had protruded into maxillary and ethmoid sinus. No obvious intracranial extension was noticed. His MRI showed 4.1 × 3.5 × 4.3 cm hyperintense lesion in the retrobulbar region on T2 weighted image. The left optic nerve was displaced superiorly and encased by the lesion and superior ophthalmic vein was involved by lesion [Figure 1]b and [Figure 1]c. He underwent a diagnostic tru-cut biopsy which suggested malignant SFT. The case was discussed in tumor board and the treatment plan and possible outcomes were discussed with the patient and with his consent left orbital exenteration was done.
Grossly, the left orbital exenteration specimen showed a greyish-brown, fleshy retrobulbar tumor measuring 4 × 3.9 ×2.9 cm. The tumor encased the optic nerve, but the eyeball and optic nerve was free of tumor [Figure 1]d. Microscopically, in most areas, the tumor was highly cellular with only focal hypocellular areas. The tumor showed spindle and epithelioid cells with enlarged hyerchromatic spindled nuclei and eosinophilic cytoplasm arranged in patternless fashion. The tumor exhibited focal areas having morphology typical of SFT with storiform pattern and staghorn-type vascularity. Mitotic count was 15/10 hpf. Large areas of tumor necrosis were seen. The tumor infiltrated retrobulbar ocular muscles [Figure 2]. The tumor was involving posterior soft tissue margin. | Figure 2: H and E sections showing (a) a spindle cell tumor behind uninvolved eyeball (×40) (b) areas exhibiting typical SFT morphology with a storiform pattern (×200) (c) thin walled staghorn type vascularity (×200) (d) spindle to epithelioid cells exhibiting nuclear atypia (×400) (e) increased mitoses (arrows) (×400) (f) foci of tumor necrosis (×100)
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On immunohistochemistry (IHC), the tumor cells expressed CD34, vimentin and showed strong nuclear expression of STAT6 [Figure 3]. Tumor cells were negative for cytokeratin, epithelial membrane antigen, desmin, smooth muscle antigen and S-100 [Figure 4]. Ki-67 proliferation index was around 20%. With these morphological and IHC features, a diagnosis of recurrent orbital malignant SFT was made. | Figure 3: IHC-Tumor cells expressing (a) CD34 (b) vimentin (c) and (d) showing bright nuclear expression of STAT6. [(a),(b) and (d) ×400, (c) ×100]
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 | Figure 4: IHC-Tumor cells were negative for (a) desmin (b) CK (c) SMA and (d) S-100 [(a) ×100, (b) and (c) ×200, (d) (×400)]
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In view of malignancy with positive posterior soft tissue margin, adjuvant radiation was given to the left orbit. He is on regular follow-up since last 18 months. Currently, he is disease free.
| Discussion | | |
SFTs are locally aggressive, slow-growing mesenchymal tumors primarily affecting the pleura.[2] Over 50% of them are in the thoracic cavity, but extra-thoracic tumors also have been reported in many sites.[5] About 6%–18% of all SFT arise in the head and neck region including orbit.[2],[6] Till date, approximately 150 cases of OSFT have been reported in the world literature.[3]
OSFTs are most often found in middle-aged adults in the 5th decade with equal gender distribution. The commonest clinical presentation is a unilateral painless proptosis, orbital mass, limitation of extraocular muscle movements.[2],[5] OSFT is characteristically usually small in size (range: 1–3 cm) at presentation as it produces symptoms early in its clinical course. It does not often indent the globe or cause compression of the optic nerve.[1] In our case, in spite of having recurrence, the patient presented late and by the time he reported to us his orbital mass was significantly increased in size with loss vision. Due to this delay, the tumor had encased the optic nerve entirely and adhered to the globe.
As clinical signs and radiological features are not distinctive, the histological examination plays an important role in the diagnosis of OSFT.[5]
Histologically, the tumor reveals alternating cellular and hypocellular areas with spindle cells having an ovoid and irregular nucleus, inconspicuous nucleoli, and a scant, undefined eosinophilic cytoplasm. Spindle cells grow in a haphazard manner in a variable cellular stroma described as a “patternless pattern.” The tumor shows thick bands of collagen interspersed between the tumor cells, branching thin-walled vessels of varying caliber, and a “staghorn” vascular pattern.[5]
Malignant SFTs may occur de novo or by transformation from benign tumors.[7] The incidence of malignancy among OSFT is around 6%–12%.[3] Several criteria have been proposed for diagnosis of malignancy in SFT. These include: age, tumor size, positive surgical margins, high cellularity, nuclear pleomorphism, tumor necrosis, and mitoses ≥ 4/10 hpf.[5],[6]
Immunohistochemically, a strong and consistent positivity of CD34 is an important diagnostic marker of SFT. It is expressed in 90 – 100 of cases but the expression of CD34 may be lost in malignant tumors.[5] SFT also shows immunoreactivity to CD99 and variable reactivity to Bcl-2. SFT is negative for desmin, keratin, EMA, S-100 protein, and SMA.[2] Nuclear STAT6 immuno-expression is quite sensitive and specific for distinguishing SFT from its mimics. Diffuse nuclear expression of STAT6 protein represents the presence of the pathognomonic NAB2:STAT6 gene fusion, caused by intra-chromosomal rearrangements on chromosome 12q.[4] It carries a diagnostic sensitivity estimate above 95%.[6] However, nuclear STAT6 staining may be absent in occasional cases; hence, a combination of STAT6 and CD34 is important with proper clinicopathological context.[2],[8] Strong expression of p53 and Ki-67 >10%, have been associated with worse outcomes and aggressive behavior of the tumor.[2]
The differential diagnosis of malignant OSFT includes other malignant spindle cell tumors like fibrosarcoma, malignant melanoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and leiomyosarcoma. Immunohistochemical expression of CD34 and STAT6 helps to differentiate malignant OSFT from its mimics.[2],[7]
Various multivariate risk assessment models have been used to predict the prognosis and the metastatic risk. The most commonly used model for thoracic and extrathoracic SFTs incorporates mitotic count, patient age, tumor size, and tumor necrosis. Using this four-variable model, tumors are grouped into low, intermediate, and high-risk groups. Tumors classified as low and intermediate risk have 0% and 10% risk of metastasis at 10 years, respectively and tumors in high-risk category have 73% risk of metastasis at 5 years.[9]
Orbital tumors tend to show a higher frequency of local recurrence than distant metastasis. About 26% of orbital SFT develop local recurrence and 2.1% develop metastatic disease, exactly opposite to that reported for SFTs in general, where 26% develop metastatic disease and 10% have local recurrence. This high recurrence rate in orbital SFT can be predicted by a risk stratification model unique to orbital tumors. This risk prediction model is based on age >45 years, tumor size >3 cm, tumor necrosis, mitosis of >4/2 mm2, moderate to high cellularity, and moderate to severe pleomorphism. Using these variables, four risk groups for recurrence are suggested: very low (score 0), low (score 1–2), intermediate (score 3–4), and high (score 5–9). With late recurrence common, long-term clinical follow up is recommended.[10] Our case recurred as an MT after a latent period of eight years. We reviewed the morphology of previously excised tumor which was typical of SFT. With age of 49 years at first presentation, size of 4 cm, lack of nuclear pleomorphism, mitoses, tumor necrosis, and with low cellularity, our case belonged to an intermediate-risk category in Thompson risk model (score 3) and low-risk category (score 0) in Demicco risk stratification model, thus supporting Thompson et al's proposition that orbital SFTs require a risk stratification system separate from that for SFTs at other extrapleural anatomical locations.
MT in recurrent SFT has been described in various other sites like lung, pleura, and thigh.[5] Jackson et al. in 2021 did an extensive review of all OSFT cases (around 150) reported in the world literature previously. They identified recurrence in 43 cases of OSFT with an interval of 6–33 years. In their extensive review, they found only 10 cases of MT in recurrent OSFT in the world literature.[3] However, they missed the only Indian case of MT in recurrent OSFT reported by Chakrabartty et al.[11] To the best of our knowledge, this is overall the 12th and just second Indian case of MT in recurrent OSFT.
Regardless of the histologic subtype, complete surgical excision with negative margins is the best approach for primary and recurrent OSFT.[2] Jackson et al., after extensive review of all OSFT cases reported so far, formulated an algorithm for the management of incompletely excised OSFTs. According to them, incompletely resected and histologically malignant tumors with positive margins are treated with adjuvant orbital radiation and targeted chemotherapy is reserved for systemic metastasis. They suggest serial imaging at three to five years for both benign and malignant SFTs and even recommend serial imaging at increasing intervals preferably for an indefinite period.[3] In our case, the patient discontinued the medical follow-up and imaging one year after first surgery and took consultation only after the recurrent tumor caused loss of vision. OSFT have a 10-year overall survival rate ranging from 45% to 89% after complete surgical excision of localized disease.[12]
In conclusion, identification of malignancy in orbital SFT is important for the patient to receive appropriate postoperative treatment, as seen in the present case.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 3. | Jackson CH, Hunt BC, Harris GJ. Fate and management of incompletely excised solitary fibrous tumor of the orbit: A case series and literature review. Ophthalmic Plast Reconstr Surg 2021;37:108-17. |
| 4. | DeVito N, Henderson E, Han G, Reed D, Bui MM, Lavey R, et al. Clinical characteristics and outcomes for solitary fibroustumor (SFT): A single center experience. PLoS ONE 2015;10:e0140362. |
| 5. | Shen J, Li H, Feng S, Cui H. Orbital solitary fibrous tumor: A clinicopathologic study from a Chinese tertiary hospital with a literature review. Cancer Manag Res 2018;10:1069-78. |
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| 7. | Wang X, Qian J, Bi Y, Ping B, Zhang R. Malignant transformation of orbital solitary fibrous tumor. Int Ophthalmol 2013;33:299-303. |
| 8. | Kao YC, Lin PC, Yen SL, Huang SC, Tsai JW, Li CF, et al. Clinicopathological and genetic heterogeneity of the head and neck solitary fibrous tumours: A comparative histological immunohistochemical and molecular study of 36 cases. Histopathology 2016;68:492-501. |
| 9. | Demicco EG, Wagner MJ, Maki RG, Gupta V, Iofin I, Lazar AJ, et al. Risk assessment in solitary fibrous tumors: Validation and refinement of a risk stratification model. Modern Pathol 2017;30:1433-42. |
| 10. | Thompson LDR, Liou SS, Feldman KA. Orbital solitary fibrous tumor: A proposed risk prediction model based on a case series and comprehensive literature review. Head Neck Pathol 2021;15:138-52. |
| 11. | Chakrabartty H, Singhvi S, Purohit D, Mittal RS. Malignant solitary fibrous tumour of orbit. Asian J Neurosurg 2017;12:55-7. [ PUBMED] [Full text] |
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Correspondence Address:
Jaydeep N Pol,
Department of Pathology, Mahatma Gandhi Cancer Hospital, Miraj – 416 410, Maharashtra
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijpm.ijpm_713_21
[Figure 1], [Figure 2], [Figure 3], [Figure 4] |
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