Synovial sarcoma

We report a hepatic monophasic synovial sarcoma in a 60-year-old woman who presented with right upper quadrant pain subsequent to an intrahepatic bleed from a highly vascular tumor mass. Imaging studies showed a dominant tumor mass in the right hepatic lobe with multiple satellite nodules. A detailed physical examination and radiologic workup failed to reveal a primary tumor elsewhere. A right partial hepatectomy was performed with a preoperative differential diagnosis of angiosarcoma versus hepatocellular carcinoma. The morphologic, immunophenotypic, and cytogenetic findings (t(X;18)(p11.2;q11.2)) were consistent with a monophasic synovial sarcoma. Postoperative clinical evaluation of the extremities and a positron emission tomographic scan performed 4 weeks after surgery showed no evidence of recurrent or metastatic disease. The patient was started on an aggressive 4-drug chemotherapy regimen, but died 3 months thereafter from widespread metastatic disease. No autopsy was performed. The presence of multiple lesions in the liver certainly suggests the possibility of metastatic disease. It would, however, be very unusual for a synovial sarcoma to present as an occult primary, and the negative radiologic workup 1 month after the partial hepatectomy also argues against this possibility. The clinical presentation, radiographic findings, and subsequent course in this patient was therefore most consistent with a primary monophasic synovial sarcoma of the liver.

(Arch Pathol Lab Med. 2005;129:1047-1049)

A synovial sarcoma is a tumor of uncertain histogenesis that occurs chiefly in young adults and has a predilection for the deep soft tissues of the para-articular regions of the extremities. It has also been described in a variety of other locations, including the orofacial and oropharyngeal region, larynx, abdominal and chest wall, retroperitoneum, lung, pleura, esophagus, heart, blood vessels, middle ear, kidney, vulva, brain, mediastinum, prostate, salivary glands, and bone.1 Recent studies have demonstrated the usefulness of cytogenetic and molecular analysis for definitive diagnosis of this lesion, especially when it arises in unusual anatomic sites.23 The t(X; 18)(pll.2;qll.2) translocation and the chimeric gene SYTSSX are felt to be specific for synovial sarcomas and are consistently found in both the biphasic and monophasic types. We describe the case of a 60-year-old woman who presented with right upper quadrant pain subsequent to an intrahepatic bleed from a highly vascular spindle cell tumor with cytogenetic evidence of a t(X;18)(pll.2;qll.2) translocation consistent with monophasic synovial sarcomas.

REPORT OF A case

A 60-year-old woman presented with an acute onset of right upper quadrant pain. Computerized tomography showed a dominant tumor mass in the right lobe of her liver measuring 10 cm in the greatest dimension with multiple satellite nodules. The pain was ascribed to an intrahepatic bleed from a highly vascular tumor. Physical examination and radiologie evaluation did not show evidence of a primary tumor in the extremities or the thoracic and abdominal cavities. The preoperative differential diagnosis was primarily between hepatocellular carcinoma and angiosarcoma. A right hepatic lobectomy was performed, which showed a malignant spindle cell tumor with morphologic, immunophenotypic, and cytogenetic features of a monophasic synovial sarcoma. Follow-up evaluation with a positron emission tomographic scan 4 weeks following surgery showed no evidence of recurrent or metastatic disease. The patient was started on a 4-drug chemotherapeutic regimen, but died after 3 months from widespread metastatic disease involving the peritoneal cavity, liver, and lungs.

MATERIALS AND METHODS

Representative areas from the resected partial hepatectomy specimen were sampled, and 5-µm sections from the formalinfixed, paraffin-embedded tissue were used for routine light microscopic study as well as immunohistochemical analysis. Immunohistochemical stains were performed by a labeled streptavidin-biotin system and the alkaline phosphatase technique using commercially available monoclonal antibodies and AEC as the chromogen. The pertinent details of the antibodies used are summarized in the Table. Small fragments of tumor tissue were also fixed in 3% glutaraldehyde in 0.2M sodium-phosphate buffer and processed routinely for electron microscopy.

GTG-banded metaphase cells were obtained and analyzed from a short-term culture (3 days) after an overnight collagenase disaggregation of a portion of the fresh tumor specimen.

PATHOLOGIC FINDINGS

The resected right hepatic lobe measured 22 × 15 × 9 cm in its greatest dimension. Serial sectioning of the specimen showed 5 relatively well-circumscribed, diffusely hemorrhagic, tan-gray nodules, the largest measuring 10 cm in its greatest diameter (Figure 1). Foci of necrosis were present. The nodules were observed abutting the liver capsule and were within 0.5 cm of the closest surgical resection margin.

Microscopically, the tumor nodules were unencapsulated and had a well-defined expansile margin that compressed the adjacent hepatic parenchyma. All nodules were morphologically similar and were composed of highly cellular areas of spindle-shaped cells arranged in a fascicular or storiform growth pattern (Figure 2). Hypocellular areas with a myxoid stroma and areas with a hemangiopericytoma-like vascular pattern were also present. The tumor cells had oval-to-elongate hyperchromatic nuclei, small nucleoli, and indistinct cytoplasm (Figure 3). The mitotic activity was brisk and averaged about 20 per 10 high-power fields in the most proliferative areas. Multiple foci of vascular invasion were identified. Immunohistochemically, the tumor cells showed diffuse strong positivity for vimentin and Bcl-2 and focal weak staining with muscle-specific and smooth muscle actin and were negative for pankeratin (AEl/AE3, CAM 5,2), cytokeratin 7, cytokeratin 20, epithelial membrane antigen, desmin, SlOO protein, HMB-45, MART-1, CD34, chromogranin, synaptophysin, CD99, and carcinoembryonic antigen. Ultrastructurally, the neoplastic spindle cells were connected by numerous prominent junctions, and the cytoplasm contained rough endoplasmic reticulum, ribosomes, mitochondria, and filaments that, in some cells, formed small aggregates. Cytogenetic analysis showed several clonal abnormalities, among them an abnormal chromosome X due to a translocation of chromosomes X and 18, with the breakpoints in the SSXI and SSX2 (band XpIl) and SYT (band 18qll) gene regions (Figure 4), thereby confirming the diagnosis of a monophasic synovial sarcoma.

COMMENT

Primary sarcomas of the liver are rare. Angiosarcoma, the most common primary malignant mesenchymal tumor of the liver, accounts for merely 0.4% of all primary hepatic malignancies.4 Other primary sarcomas reported in small numbers in the literature include malignant fibrous histiocytoma,5 leiomyosarcoma,6 liposarcoma/ fibrosarcoma,8 malignant solitary fibrous tumor,9 and malignant hemangiopericytoma.10

Synovial sarcomas usually occur in adolescents and young adults in para-articular regions. Morphologically, they are subclassified into biphasic, monophasic, and poorly differentiated subtypes. The poorly differentiated synovial sarcoma may, in turn, show a large cell, small cell, or high-grade spindle cell morphology. Although the diagnosis of a synovial sarcoma may be suspected on the basis of morphology and immunophenotype (vimentin positive, keratin, and/or epithelial membrane antigen positive), recent studies have shown the usefulness of cytogenetic and molecular techniques as diagnostic adjuncts for distinguishing a synovial sarcoma from other morphologically similar spindle cell sarcomas. Moreover, an important minority of monophasic spindle cell synovial sarcomas can be negative for both cytokeratin and epithelial membrane antigen,11 and demonstration of the characteristic cytogenetic abnormality is imperative for a definite diagnosis in such cases. More recently, it has been shown that 2 closely related but distinct X-chromosomal genes (SSX1 and SSX2) are rearranged in different subsets of synovial sarcomas.12 Evidence suggests that there is a correlation between the histologie subtypes and SSXl or SSX2 involvement11 and that the SYT-SSX fusion type (SSX1 vs SSX2) has prognostic importance in patients with localized disease at diagnosis.14 The cytogenetic detection of the t(X;18)(p11.2;q11.2) translocation and the use of reverse transcriptase-polymerase chain reaction to detect the chimeric SYT-SSX fusion transcript are thus highly sensitive and specific markers for synovial sarcomas.

Although the multiple hepatic lesions observed in the present case certainly are suggestive of metastatic disease, it would be very unusual for a synovial sarcoma to present as an occult primary. Moreover, a detailed physical examination and preoperative radiologic evaluation did not show the presence of a primary lesion elsewhere. A follow-up positron emission tomographic scan 4 weeks after surgery was also negative for the tumor and argues against the possibility of metastatic disease. The presence of a dominant primary hepatic tumor with multiple satellite nodules thus seems to be the most plausible explanation in the present case. The findings in this very unusual case are therefore, in our opinion, most consistent with a primary synovial sarcoma of the liver, and they emphasize the utility of cytogenetic demonstration of the t(X;18)(p11.2;q11.2) translocation in making a definitive diagnosis.

References

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2. Fligman I, Lonardo F, jhanwar SC, et al. Molecular diagnosis of synovial sarcoma and characterization of a variant SYT-SSX2 fusion transcript. Am J Pathol. 1995;147:1592-1599.

3. Argani P, Zakowski MF, Klimstra DS, et al. Detection of SYT-SSX chimeric RNA of synovia! sarcoma in paraffin-embedded tissue and its application in problematic cases. Mod Pathol. 1998;11:65-71.

4. Ishak KC, Goodman ZD, Stocker JT. Malignant mesenchymal tumors. In: Rosai J, Sobin LH, eds. Tumors of the Liver and Intrahepatic Bile Ducts. Washington, DC: Armed Forces Institute of Pathology; 2001:281-330. Atlas of Tumor Ethology, 3rd series, fascicle 31.

5. Colovic N, Cemerikic-Martinovic V, Colovic R, et al. Primary malignant fibrous histiocytoma of the spleen and liver. Med Oncol. 2001;18:293-297.

6. Fujita H, Kiriyama M, Kawamura T, et al. Primary hepatic leiomyosarcoma in a woman after renal transplantation: report of a case. Surg Today. 2002;32: 446-449.

7. Nelson V, Fernandes NF, Woolf GM, et al. Primary liposarcoma of the liver: a case report and review of literature. Arch Pathol Lab Med. 2001;125:410-412.

8. Pinson CW, Lopez RR, Ivancev K, et al. Resection of primary hepatic malignant fibrous histiocytoma, fibrosarcoma and leiomyosarcoma. South Med J. 1994;87:384-391.

9. Yilmaz S, Kirimlioglu V, Ertaz E, et al. Giant solitary fibrous tumor of the liver with metastasis to the skeletal system successfully treated with trisegmentectomy. Dig Dis Sci. 2000;45:168-174.

10. Shi SS, Lin FS, Li TS. Primary sarcoma of the liver. Zhonghua Zhong Liu Za ZhL 1994;16:228-230.

11. Kempson RL, Fletcher CDM, Evans HL, et al. Tumors of uncertain and non-mesenchymal differentiation. In: Rosai J, Sobin LH, eds. Tumors of the Soft Tissues. Washington, DC: Armed Forces Institute of Pathology; 2001:472-484. Atlas of Tumor Pathology, 3rd series, fascicle 30.

12. de Leeuw B, Balemans M, Olde Weghuis D, et al. Identification of two alternate fusion genes, SYT-SSX1 and SYT-SSX2, in t(X:18)(p11.2:q11.2) positive synovial sarcomas. Hum Mol Genet. 1995;4:1097-1099.

13. Lasota I, Jasinski M, Debiec-Rychter M, et al. Detection of SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma. Mod Pathol. 1998;11:626-633.

14. Ladanyi M, Antonescu CR, Leung DH, et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res. 2002;62:135-140.

Amitabh Srivastava, MBBS; Petur G. Me/sen, MD; Paola DaI Cm, PhD; Andrew E. Rosenberg, MD

Accepted for publication April 1, 2005.

From the Departments of Pathology, Tufts-New England Medical Center (Dr Srivastava), James Homer Wright Laboratories, Massachusetts General Hospital (Drs Nielsen and Rosenberg), and Division of Cytogenetics, Brigham & Women's Hospital (Dr DaI Cin), Boston, Mass.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Andrew E. Rosenberg, MD, James Homer Wright Laboratories, Massachusetts General Hospital, 55 Fruit St, Warren Building, Room 225, Boston, MA 02114 (e-mail: arosenberg@partners.org).

Copyright College of American Pathologists Aug 2005
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