Secondary Logo

Journal Logo

Primary Orbital Synovial Sarcoma Mimicking a Periocular Cyst

Portelli, Francesca MD*; Pieretti, Giulia MD, PhD; Santoro, Nicola MD, PhD; Gorelli, Greta BSc*; De Giorgi, Vincenzo MD; Massi, Daniela MD, PhD*; Dei Tos, Angelo Paolo MD§; Mazzini, Cinzia MD

The American Journal of Dermatopathology: September 2019 - Volume 41 - Issue 9 - p 655–660
doi: 10.1097/DAD.0000000000001351
Brief Report
Free

Abstract: Synovial sarcoma (SS) is a high-grade soft-tissue sarcoma occurring predominantly in older children and young adults. Only approximately 7% occur in the head and neck region, with SS representing less than 0.1% of all head and neck cancers. Orbital location is exceedingly rare with only 8 cases reported so far in the literature. It is noted for its propensity for late local recurrences and metastases. Histologically, SS is monophasic, biphasic, or poorly differentiated and harbors a specific chromosomal translocation t(X;18)(p11.2;q11.2) in >95% of cases. In this article, we describe a case of monophasic SS primarily arising in the left supero-nasal orbital region in a 24-year-old woman, clinically mistaken for a periocular cyst. The case is peculiar for its highly unusual location and for its clinical deceptively benign appearance.

*Histopathology and Molecular Diagnostics, Department of Health Sciences, Careggi University Hospital, Florence, Italy;

Unit of Ocular Oncology, Department of Surgery and Translational Medicine, Careggi University Hospital, Florence, Italy;

Division of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy; and

§Department of Medicine, University of Padua School of Medicine, Padua, Italy.

Correspondence: Francesca Portelli, MD, Histopathology and Molecular Diagnostics, Department of Health Sciences, Careggi University Hospital, Largo Brambilla, 3, 50134 Florence, Italy (e-mail: portellif@aou-careggi.toscana.it).

The authors declare no conflicts of interest.

Back to Top | Article Outline

INTRODUCTION

Synovial sarcoma (SS) is a malignant mesenchymal neoplasm accounting for 5%–10% of all soft-tissue sarcomas, which occurs predominantly in older children and young adults with a slight male predominance.1 SS may occur in any anatomical site, although most tumors (70%) arise in the deep soft tissues of extremities, particularly the lower extremities, most commonly around the knee, often in a juxta-articular location. About 7% of cases have been described in the head and neck region, with SS representing less than 0.1% of all head and neck cancers.2 Orbital and ocular location is exceedingly rare with only few cases reported so far.3–12 Rare SSs metastatic to the orbit have also been described.13,14

The term SS is a historical misnomer inherited by older literature that postulated a synovial differentiation based on the propensity of the neoplasm to take origin in periarticular regions.15 The specific cell of origin of SS is unknown, and neural, myogenic, or multipotent mesenchymal stem cell has been considered as putative originators.16

SS typically manifests as a progressive slowly growing mass within deep soft tissues, associated with local pain and tenderness in more than half of cases.1 Histologically, SS may appear as monophasic, entirely composed of spindle cells, biphasic with epithelial cells arranged in glandular structures and uniform spindle cells and poorly differentiated exhibiting a large-cell or epithelioid pattern, a small-cell pattern or a high-grade spindle-cell pattern composed of spindle-shaped cells with high-grade nuclear features.1,17 Immunohi-stochemically, more than 90% of SSs show focal expression of epithelial markers, epithelial membrane antigen (EMA) and cytokeratins; focal expression of S100 protein is seen in approximately 40% of cases.1 Diagnosis of SS is based on the presence of the t(X;18)(p11.2;q11.2) translocation, involving the SS18 (formerly SYT) gene on chromosome 18 and at least one of several synovial sarcoma X genes on chromosome X, which is uniquely found in >95% of SSs.1

In this article, we report on the challenging diagnosis of a primary orbital monophasic SS, which clinically appeared as a periocular cyst in a 24-year-old woman, and review the clinicopathological features of SS in this exceedingly rare location.

Back to Top | Article Outline

CASE REPORT

A 24-year-old woman presented with a 1-year history of gradually growing occasionally painful cystic lesion in the left superonasal orbital region (Fig. 1). On ophthalmologic examination, visual activity was 20/20 in both eyes, pupillary reactions were normal, extraocular motility was full with no diplopia, and fundus examination was normal. The preoperative orbital ultrasound revealed a hypoechogenic uniform roundish lesion, 14 × 7.5 mm in size (Fig. 2), clinically suspicious of a cyst. At surgery, a clear plane of dissection was not evident, so that multiple fragments of the lesion were taken and sent to pathology for intraoperative examination, which resulted in a spindle cell neoplasm. The lesion was then partially removed because complete removal was not possible and sent for definitive histopathologic examination.

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

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).

FIGURE 3

FIGURE 3

FIGURE 4

FIGURE 4

FIGURE 5

FIGURE 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.

FIGURE 6

FIGURE 6

Back to Top | Article Outline

DISCUSSION

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

TABLE 1-a

TABLE 1-a

TABLE 1-b

TABLE 1-b

Back to Top | Article Outline

CONCLUSIONS

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.

Back to Top | Article Outline

REFERENCES

1. Thway K, Fisher C. Synovial sarcoma: defining features and diagnostic evolution. Ann Diagn Pathol. 2014;18:369–380.
2. Owosho AA, Estilo CL, Rosen EB, et al. A clinicopathologic study on SS18 fusion positive head and neck synovial sarcomas. Oral Oncol. 2017;66:46–51.
3. Thomas CH, Guillemin M. Synovialosarcome typique et primitif de l'orbite. Doc Ophthalmol. 1966;20:484–499.
4. Ratnatunga N, Goodlad JR, Sankarakumaran N, et al. Primary biphasic synovial sarcoma of the orbit. J Clin Pathol. 1992;45:265–267.
5. Votruba M, Hungerford J, Cornes PG, et al. Primary monophasic synovial sarcoma of the conjunctiva. Br J Ophtalomol. 2002;86:1453–1454.
6. Shukla PN, Pathy S, Sen S, et al. Primary orbital calcified synovial sarcoma: a case report. Orbit. 2003;22:299–303.
7. Hartstein ME, Silver FL, Ludwig OJ, et al. Primary synovial sarcoma. Ophthalmology. 2006;113:2093–2096.
8. Liu K, Duan X, Yang L, et al. Primary synovial sarcoma in the orbit. J AAPOS. 2012;16:582–584.
9. Ito J, Suzuki S, Yoshida A, et al. Primary intraocular synovial sarcoma in the post retinal detachment operative state. BMJ Case Rep. 2015;6:2015.
10. Stagner AM, Jakobiec FA, Fay A. Primary orbital synovial sarcoma: a clinicopathologic review with a differential diagnosis and discussion of molecular genetics. Surv Ophthalomol. 2017;62:227–236.
11. Xu P, Chen J. Primary synovial sarcoma of the orbit. Ophthalomol Eye Dis. 2017;9:1179172117701732.
12. Richards NQ, Kofler JK, Chu CT, et al. Intraocular synovial sarcoma. Retin Cases Brief Rep. 2017;11:302–305.
13. Buono LM, Silberschmidt A, Foroozan R, et al. Metastatic synovial sarcoma to the skull base and orbit. Am J Ophthalmol. 2002;134:785–787.
14. Wladis EJ, Farber MG, Nepo AG. Metastatic synovial sarcoma to the orbit. Ophthalmic Plast Reconstr Surg. 2012;28:e131–132.
15. Nielsen TO, Poulin NM, Ladanyi M. Synovial sarcoma: recent discoveries as a roadmap to new avenues for therapy. Cancer Discov. 2015;5:124–134.
16. Garcia CB, Shaffer CM, Alfaro MP, et al. Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2. Oncogene. 2012;31:2323–2334.
17. Bianchi G, Sambri A, Righi A, et al. Histology and grading are important prognostic factors in synovial sarcoma. Eur J Surg Oncol. 2017;43:1733–1739.
18. Malignant soft tissue tumors of uncertain type. In: Goldblum JR, Folpe AL, Weiss SW, eds. Enzinger and Weiss's Soft Tissue Tumors. Philadelphia, PA: Elsevier Saunders; 2014:1052–1070.
19. Eagle RC. Orbit. In: Eagle RC, ed. Eye Pathology. An Atlas and Text. Philadelphia, PA: Wolters Kluwer; 2017:302–313.
20. Krieg AH, Hefti F, Speth BM, et al. Synovial sarcomas usually metastasize after >5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors. Ann Oncol. 2011;22:458–467.
Keywords:

synovial sarcoma; orbit; eye; periocular cyst; translocation t(X;18)

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.