Monophasic Synovial Sarcoma Tina Fanning MD Anderson Cancer Center Houston, TX

Clinical History A 25 year old male presented with a two month history of right parotid gland swelling. Slide 1 - Cell Block Click to view with ImageScope Click to view with a Web-Based Viewer Slide 2 - DiffQuik Click to view with ImageScope Click to view with a Web-Based Viewer Slide 3 - Pap Stain Click to view with ImageScope Click to view with a Web-Based Viewer Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Diagnosis: Monophasic Synovial Sarcoma Synovial Sarcoma: Definition: a biphasic soft tissue with epithelial and spindle cell components or a monophasic sarcoma having the same histologic features as the spindle cell component of biphasic synovial sarcoma. Synovial Sarcoma is associated with a specific balanced translocation, t(X:18)(p11.2:q11.2), in more than 90% of cases. Synovial sarcoma does not arise from joints and is not related to synovial cells. The name "synovial sarcoma" is kept by tradition. Clinical Features Age: adolescents and young adults (15-40 yrs) (may occur in children and older adults rarely) Incidence: 5-10% of soft tissue sarcomas AFIP data: MFH > liposarcoma > rhabdomyosarcoma > synovial sarcoma Radiograph: some examples are calcified Anatomic location: Extremities Especially lower extremity Thigh-knee is most common site May occur in the distal extremities Head and Neck Trunk Other sites: chest, mediastinum, heart, lung, retroperitoneum Note: it is useful to recall the three sarcomas that commonly occur in the distal extremities of young persons: synovial sarcoma, epithelioid sarcoma and melanoma of soft parts. Of interest, all three of these sarcomas metastasize to lymph node, although synovial sarcoma less frequently than the others. Synovial Sarcoma AFIP series, 345 cases Anatomic Location Percent Head-neck 9% Trunk 8% Extremities 83% Upper 23% Lower 60% Biology, Treatment, Prognosis Grade: high grade Metastasis: 50% of patients Lung (94%) Lymph node (10%) Bone marrow Treatment: Chemo: adriamysin, ifosfamide XRT Compartmental resection Prognosis: 5 year survival: 36-76% 10 year survival: 20-63% Factors Affecting Survival Lower Risk for Mets Age<25 years Tumor < 5cm No poorly differentiated areas High Risk for Mets Age > 40 years Tumor > 5cm Poorly differentiated areas Modified from Berg P, Mels-Kindblom JM, Gherlinzoni F, et.al. Cancer 1999;85:2596 Size: Synovial sarcomas vary at presentation from small tumors to very large tumors. As might be expected, smaller tumors are often located distally (i.e. foot, ankle) or in head and neck areas where they become apparent sooner. The first diagnosis of synovial sarcoma that I made on FNA was on a 31 year old tennis player who played the whole season before seeing his doctor for a mass in his thigh. In this deep tissue site, the tumor grew to a significant size (20 cm) before he sought medical attention. Despite aggressive chemotherapy, he developed pulmonary metastasis and had a short survival. Synovial Sarcoma Histologic Patterns Biphasic Synovial Sarcoma Biphasic Monophasic Epithelial Monophasic Poorly differentiated (usually round cell variant) Biphasic Synovial Sarcoma True epithelial component + Uniform spindle cell component Epithelial and spindle cell areas: intermingled but usually sharply demarcated from each other Epithelial component: solid areas with flattened, cuboidal or columnar cells with moderate cytoplasm arranged in glands, tubules, solid sheets and occasionally as papillary structures. Note: in my experience, the epithelial component of biphasic synovial sarcoma is more difficult to discern on smears than on cell block sections or core biopsies. On smears, the epithelial component may appear as areas of plumper cells merging with uniform spindle cells. Spindle cell component: small, uniform oval to tapered cells with high nuclear to cytoplasmic ratios (scant cytoplasm) arranged in sheets or fascicles with some dispersed cells. The spindle cell component is identical to the spindle cells comprising monophasic synovial sarcoma. Monophasic Synovial Sarcoma Histologic Features Uniform spindle cells Hemangioperictoma-like vascular pattern Thick collagen bundles Calcifications Evans, H.L. Synovial sarcoma. A study of 23 biphasic and 17 probably monophasic examples. Pathol. Annu; 1980; 15:309-31. Cytologic Features Cytologic diagnosis must depend on the features of the cells: Uniform spindle cells Relatively small spindle cells Plump to elongate Overall bland appearance High N/C ratio Fine granular chromatin Inconspicuous nucleoli Dense cellular packing Core Biopsies: May show hemangiopericytoma-like vascular pattern May show some collagen bundles Differential Diagnosis for Monophasic Synovial Sarcoma Fibrosarcoma Leiomyosarcoma Malignant peripheral nerve sheath tumor (MPNST) Unclassified spindle cell sarcoma Hemangiopericytoma Dermatofibrosarcoma protruberans (DFSP) Sarcomatoid carcinoma Spindle cell melanoma Poorly Differentiated (Round Cell Synovial Sarcoma) Differential Diagnosis Extraskeletal Ewing's Sarcoma Rhabdomyosarcoma Neuroblastoma Desmoplastic Round Cell Tumor Lymphoma Special Studies Epithelial component of biphasic: Cytokeratin + (especially CK9 and CK17) EMA + Spindle cell component: Variable staining with CK's and EMA (some but not all tumors show staining) Focal, less intense staining with these two markers when expressed Other markers which may be positive: S-100 protein - 33%, focal CD99 - 60% CD57 CD56 Neurofilaments BCL-2 Be careful in your differential diagnosis with spindle cell melanomas and MPNST since synovial sarcoma can be + for S-100 protein in as many as 1/3 of cases. Remember that CD99 is seen in Ewing's sarcoma, ALL/LBL, some rhabdomyosarcomas as well as in a significant number of synovial sarcomas. The staining with CD99 is important to remember in round cell "poorly differentiated" examples of synovial sarcoma so as to avoid misclassification as Ewing's sarcoma (treatment is different). Cytogenetics and Molecular Genetics Balanced reciprocal translocation between chromosomes X and 18: t(X;18) (p11.2; q11.2) Fusion proteins: SYT-SSX1 SYT-SSX2 In my experience, a good sampling of biphasic synovial sarcoma requires no more than a satisfactory histologic sample (cell blocks count!) with an H&E stain. Cytogenetics and molecular studies are of particular use in monophasic synovial sarcomas, synovial sarcomas occurring at unusual sites and in small biopsy samples showing uniform spindle cell neoplasms suspicious for synovial sarcoma. Fluorescent in situ hybridization is a particularly useful technique for FNA samples. Conventional cytogenetic studies can also be done on cytology specimens if fresh, un-fixed material is collected appropriately. I find cytogenetic/molecular studies preferable to immunohistochemistry in the evaluation of suspect monophasic synovial sarcoma since there is not a specific immunophenotype for monophasic synovial sarcoma. Immunostudies, however, may be useful in excluding or defining other entities in the differential diagnosis such as leiomyosarcoma or spindle cell melanoma. Useful Diagnostic Techniques Conventional cytogenetics Requires a fresh sample in sterile tissue culture media Fluorescent in-situ hybridization Can be done on fixed cytology smears, cytospins, cell blocks, cores RT-PCR for fusion proteins Can be done of cell blocks, core biopsies General References: Weiss SW, Goldblum JR, eds. Enzinger and Weiss's Soft Tissue Tumors, 4th. ed. (2001), Mosby:St. Louis. Kempson RL, Fletcher CDM, Evans HL, Hendrickson MR, Sibley RK. Tumors of the Soft Tissues. Atlas of Tumor Pathology, 3rd series, Fascicle 30. Washington, DC:Armed Forces Institute of Pathology, 2001. Classic Description of Monophasic Variant: Evans HL. Synovial Sarcoma: a study of 23 biphasic and 17 probable monophasic examples. Pathol Annu 15:309, 1980. Synovial Sarcoma of the Head and Neck: Amble FR, Olsen KD, Nascimento AG, et.al. Head and Neck Synovial Cell Sarcoma. Otolaryngol Head Neck Surg 107:631, 1992. Carrillo R, Rodriguez-Peralto JL, Batsakis JG, Synovial Sarcomas of the Head and Neck. Ann Otolaryngol Rhinol Laryngol 101;367-70, 1992. Grayson W, Nayler SJ, Jena GP. Synovial Sarcoma of the Parotid Gland: a case report with clinicopathologic analysis and review of the literature South Afr J Surg 36:32, 1998. Holtz F, Magielski JF, Synovial Sarcomas of the Tongue Base: the seventh reported case. Arch Otolaryngol 111:271, 1985. Knight JC, Reeves BR, Kearney L, et.al. Localization of the Synovial Sarcoma t(x;18)(p11.2;q11.2) Breakpoint by Fluorescence In-situ Hybridization. Hum Mol Genet 1:633-637, 1992. Massarelli G, Tanda F, Salis B. Synovial Sarcoma of the Soft Palate: report of a case. Hum Pathol 9:341, 1978. Roth JA, Enzinger FM, Tannenbaum M. Synovial Sarcoma of the Neck: a follow-up study of 24 cases. Cancer 35:1243-1253, 1975. Cytology References: Akerman M, Willen H, Carlen B, Mandahl N, Mertens F. Fine Needle Aspiration of Synovial Sarcoma-a comparative histological-cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination of DNA-ploidy analysis. Cytopathology 7:187-200, 1996. Kilpatrick SE, Teot LA, Stanley MW, et.al. Fine-Needle Aspiration Biopsy of Synovial Sarcoma. A Cytomorphologic Analysis of Primary, Recurrent, and Metastic Tumors. Am J. Clin Pathol 106:769-775, 1996b. Kindblom LG, Walaas L, Widehn S. Ultrastructural Studies in the Preoperative Cytologic Diagnosisof Soft Tissue Tumors. Semin Diagn Pathol 3:317-344, 1985. Ryan MR, Stastny JF, Wakely PE. The Cytopathology of Synovial Sarcoma: a study of six cases, with emphasis on architecture and histopathologic correlation. Cancer 84:42-49, 1998. Viguer JM, Jimenez-Heffernan JA, Vicandi B, et.al. Cytologic Features of Synovial Sarcoma with Emphasis on the Monophasic Fibrous Variant: a morphologic and immunocytochemical analysis of bcl-2 protein expression. Cancer 84:50-56, 1998.