On gross examination, the resected material consisted of multiple whitish fragments. Histological examination showed a spindle cell proliferation, composed of relatively small and fairly uniform cells with ovoid or elongated nuclei and eosinophilic cytoplasm arranged in hypercellular packed sheets and vague fascicles. The stroma was focally myxoid, thus leading to hypocellular areas. Poorly differentiated areas, calcifications, hemorrhage, and necrosis were not observed. Two mitoses/10 high-power field were counted. Immunohistochemically, the neoplastic cells were focally positive for EMA, AE1/AE3, S100 protein, and TLE1, diffusely positive for bcl-2 and negative for CK7, CK19, CD99, CD34, MDM2, SOX-10, desmin, and muscle-specific actin. The Ki-67 proliferation index was approximately 5% (Figs. 3 and 4). Fluorescence in situ hybridization (FISH) was performed with Vysis SS18 Break Apart FISH Probe Kit (Abbott Molecular Inc, Des Plaines, IL) and was positive for SYT gene rearrangement (Fig. 5).
Histological, immunohistochemical and molecular findings were consistent with a monophasic SS. The tumor was classified as grade 2 according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC).
A postoperative magnetic resonance imaging (MRI) of the orbits showed a residual ovalar lesion, approximately 12 mm in size (Fig. 6). The patient underwent systemic workup, with no evidence of metastases. A second surgical intervention with a complete removal of the mass was then undertaken, without ocular complications. No adjuvant treatment was undertaken. The patient is free of recurrences and metastases after 20 months of follow-up.
Our case presents peculiar clinical and histopatholo-gical features. First, the clinical appearance was consistent with a slowly growing cystic lesion, suggesting the hypothesis of a sebaceous cyst. Nothing abnormal was detected on ophthalmologic examination, and pain was the unique symptom referred by the patient, although reported only occasionally. The overall clinical picture was not worrisome and seemed to be attributable to a benign lesion. But, at surgery, the lesion appeared firm in consistency and not well circumscribed. The clinical deceptively benign appearance misleaded the clinician, and the histological diagnosis was unexpected.
Histologically, the differential diagnosis included malignant peripheral nerve sheath tumor (MPNST), leiomyosarcoma (LMS), fibrosarcoma (FS), and solitary fibrous tumor (SFT).
Spindle cell MPNST, the variant most resembling SS, typically shows long fascicles or an FS-like herringbone pattern of cells with elongated wavy nuclei and scanty cytoplasm and may exhibit hypercellular and hypocellular areas.1 In our case, the cells were mostly arranged in sheets and vague fascicles, with alternating hypercellular and hypocellular myxoid areas, and no FS-like areas were observed. Similarly to SS, MPNST can express S100 protein, EMA, CK7, CK19, TLE1, and SOX10; CD34 is virtually absent in SS, whereas it can be focally expressed by MPNST. In our case, the neoplasm was negative for CK7, CK19, SOX10, and CD34.
LMS is composed by better-defined intersecting fa-scicles of cells, the nuclei are blunt-ended, and the cytoplasm is more densely eosinophilic. Although LMS can show focal cytokeratin and rare EMA expression, this tumor shows marked staining for smooth muscle actin, h-caldesmon, and desmin.1 In our case, the fascicles of cells were loose, longer, and more ample rather than intersecting, and the muscular markers were negative.
SS may closely simulate FS, although SS is generally composed of more ovoid-appearing cells arranged in an irregular fascicular growth pattern. The presence of mast cells and the immunohistochemical expression of AE1/AE3, EMA, and TLE1 further proposed the diagnosis of SS.18
SFT may be highly cellular, with round to fusiform cells, resembling the hypercellular areas of SS, but they are arranged in short ill-defined fascicles and randomly in a patternless pattern, with prominent thin-walled hemangiopericytic vessels and usually striking hyalinization. In our case, spindle cells were arranged in loose fascicles; prominent hemangiopericytic vessels and hyalinized areas were not present. Immunohistochemically, the negativity for CD34 and STAT6 (expressed by SFT) were useful negative findings because SFT may rarely express cytokeratins.18 In conclusion, the integration of the histological and immunohistochemical findings with the molecular confirmation of the t(X;18) translocation allowed to render a definitive diagnosis of SS.
Orbital localization of SS is exceedingly rare. Soft-tissue orbital tumors more frequently reported in adults include schwannomas and SFTs, rhabdomyosarcoma in infants and young children.4,19 To the best of our know-ledge, only 8 cases of primary orbital SSs3,4,6–8,10,11 and, interestingly, 3 cases of primary ocular SSs5,9,12 have been reported in the literature. Table 1 summarizes all the reported cases. These cases showed an age range from 1.5 to 54 years (median age: 29 years) with a slight female predominance (male: female ratio of approximately 1.7). With respect to the 3 cases with ocular localization, in one case, the tumor presented as a growing conjunctival lesion at the medial canthus of the right eye5; in another case, it was intraocular, confined to the left eyeball of a patient with a history of retinal detachment surgery, vitrectomy, and silicon explant9; and in a third case, the tumor was incidentally found in a blind painful enucleated eye.12 Clinically, pain, proptosis, exophthalmia, orbital swelling, diplopia, decreased visual activity, and limited ocular motility were recorded. In 7 cases, the tumor was adherent to extraocular muscles. Calcifications were described in 3 cases. Histologically, 3 cases were classified as monophasic, 5 cases as biphasic, and 3 cases as poorly differentiated SS. Regarding the treatment, exenteration was performed in 3 cases, partial excision in 2 cases, complete excision in 1 case, partial excision and adjuvant radiothe-rapy in 2 cases, excision and adjuvant chemotherapy in 2 cases, and radiotherapy to decrease the exophthalmia followed by exenteration years later in 1 case. Follow-up was available in only 6 cases, ranging from 6 months to 4 years. No recurrences or metastases are documented even in those cases with a partial or subtotal excision of the tumor, but the limited number of cases reported to date and the limited follow-up do not allow for any significant conclusion. In our case 2 surgical interventions were necessary to remove completely the tumor. No adjuvant therapy was undertaken, and no evidence of recurrence and metastasis were detected after 20 months of follow-up. In the literature, 5-year survival for SS ranges from 25% to 75% and 10-year survival from 11% to 63%. Significant adverse prognostic factors for SS include larger tumor size, metastases at diagnosis, high histological grade, trunk-related disease, and intralesional or marginal surgery. Based on the high rate of local recurrence and metastases even after 5 and 10 years, all patients should be followed for >10 years.20
In conclusion, when evaluating a periocular cystic-appearing lesion, SS must be considered in the differential clinical diagnosis, especially in young patients. Ophthalmo-logists and pathologists should be aware of this rare occurrence for which local control and long follow-up are needed.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
synovial sarcoma; orbit; eye; periocular cyst; translocation t(X;18)