Synovial sarcoma

Originally thought to arise from synovial cells, this tumour probably arises from pluripotential mesenchymal cells capable of partial or aberrant epithelial differentaition²⁴.

This tumour accounts for approximately 10% of all soft tissue sarcomas⁷ and commonly arises in the para-articular deep soft tissues of the extremities of young adults. It has also been identified in the head and neck area^15,18,22,23 including the third ventricle²⁵, thorax (mediastinum, pleura, heart, lung⁵, heart, chest wall, pharynx, larynx), abdominal wall¹⁷, retroperitoneum^27,28, mesentry²⁶, kidney^16,20, prostate^19,29, vulva²¹ and peritoneal cavity.

Synovial sarcomas show a specific chromosomal translocation, t(X:18)(p11.2;q11.2), which results in fusion of the SYT gene on the long arm of chromosome 18 with the SSX1, SSX2 or SSX4 gene on the short arm of the X chromosome. The transcript of the fusion gene can be demonstrated by reverse transcriptase-polymerase chain reaction in more than 90% of cases^5,6 and may be identified from paraffin-embedded tissue by in situ hybridisation.

Variants

• biphasic
  

• monophasic epithelial
  

• monophasic fibrous
  

• poorly differentiated
  

• cystic
  

• myxoid

Rarely, synovial sarcoma may show extensive calcification and ossification² or cartilage formation. The existence of a pure epithelial variant is controversial, but may be diagnosed on a deep seated soft tissue tumour in a patient who fails to declare an epithelial primary after several years⁴.

Immunohistochemistry

EMA	up to 90%, 1/1 (small mesenteric synovial sarcoma: both epithelial and spindle cell components positive)26
Ca15.3	positive
low MW cytokeratins	60-70%
bcl-2	93%
S-100	30%3
CD30	rarely
CD99	48%
CD117	some
CNA.42	positive
CD34	negative
Microphthalmia transcription factor	negative
tyrosinase	negative
Cytokeratin 1	14/2210
Cytokeratin 5/6	9/3710
Cytokeratin 7	73/8110
Cytokeratin 8 / 18	88/8810
Cytokeratin 10	4/1810
Cytokeratin 13	15/638
Cytokeratin14	39/4410
Cytokeratin 19	53/533
Cytokeratin 20	0/61, 12/45 (summary data from reference 10, excluding reference 1)10
vimentin	2/25, 1/1 (small mesenteric synovial sarcoma: epithelial component focally positive)26
desmin	1/1 (small mesenteric synovial sarcoma: epithelial component focally positive)26
SMA	0/25
Muscle-specific actin	0/25
CD34	0/25
b-catenin	44/447

A study of monophasic fibrous and poorly differentiated synovial sarcomas, with the diagnosis established by the presence of the translocations t(X:18)(p11.2;q11.2) has shown that reactivity for EMA, AE1/AE3 and E-cadherin, combined with negativity for CD34 is the most useful combination of markers for these problematic types of synovial sarcoma⁹.

The proliferative indices and expression of the pro-apoptotic factor bax are higher in the solid/glandular component than in the spindle cell component¹¹. The latter shows a greater expression of the anti-apoptotic factor bcl-2¹¹. The SYT-SSX1 is associated with biphasic morphology¹³ and a higher proliferative index¹².

	solid-glandular component			spindle cell component
	<10%	10-30%	>30%	<10%	10-30%	>30%
Ki67	2/1011	8/1011	0/1011	10/1011	0/1011	0/1011
bcl-2	6/1011	4/1011	0/1011	2/1011	3/1011	5/1011
AE1/AE3	0/1011	1/1011	9/1011	10/1011	0/1011	0/1011
Vimentin	9/1011	0/1011	1/1011	2/1011	4/1011	4/1011
bax	2/811	5/811	1/811	8/811	0/811	0/811

Differential diagnosis: see the immunohistochemistry of the differential diagnosis of spindle cell stromal tumours of the pleura. The t(X:18)(p11.2;q11.2) seems to have both specificity and sensitivity for synovial sarcoma and is extremely useful in cases of doubt

• malignant peripheral nerve sheath tumour
  

• fibrosarcoma
  

• leiomyosarcoma
  

• malignant haemangiopericytoma
  

• Ewing's sarcoma/PNET

Reference9	cytokeratin	EMA	S-100	CD99	bcl-2
MPNST	some, focally	some focally	50-70%	some focally	some focally
cellular Schwannoma			diffusely strongly
spindle cell melanoma			diffusely strongly
solitary fibrous tumour				positive	positive
giant cell angiofibroma				some	some
lipomatous haemangiopericytoma				some	some
sclerosing epithelioid fibrosarcoma				some	some
epithelioid sarcoma	positive
Ewing's sarcoma/PNET	positive			some	some
leiomyosarcoma	some
rhabdomyosarcoma	some

Prognosis

The five and ten year survival rates in one study were 68% and 41% respectively. Variables associated with an adverse outcome included tumour size >6.7 cm, poorly differentiated subtype, high nuclear atypia, mitotic count > 27/10 high-power fields, absence of stromal calcification, nuclear expression of b-catenin and Ki-67 (MIB-1) index > 27%⁷. A high proliferation rate and poor prognosis are associated with the SYT-SSX1 translocation¹⁴.

References

¹ Miettinen M. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial and Merkel cell carcinomas. Mod Pathol 1995;8:384-388.

² Winnepenninckx V et al. Calcifying/ossifying synovial sarcoma shows t(X;18) with SSX2 involvement and mitochondrial calcification. Histopathology 2001;38:141-145.

³ Diagnostic histopathology of tumors. Edited by CDM Fletcher. 2nd edition. Churchill Livingstone. Page 1525.

⁴ Tajima, K., Fuyama, S., Yamaguchi, H., Ohrui, H., Suzuki, K., Akiba, J., Yahagi, A., Hayashi, T., Satoh, S., Katoh, T. Pure monophasic, epithelial synovial sarcoma without a spindle cell component Histopathology 1999;34:78-81.

⁵ Hisaoka, M., Hashimoto, H., Iwamasa, T., Ishikawa, K., Aoki, T. Primary synovial sarcoma of the lung: report of two cases confirmed by molecular detection of SYT-SSX fusion gene transcripts. Histopathology 1999;34:205-210

⁶ Guillou, L., Coindre, J., Gallagher, G., Terrier, P., Gebhard, S., de Saint Aubain Somerhausen, N., Michels, J., Jundt, G., Vince, D. R., Collin, F., Trassard, M., Le Doussal, V., Benhattar, J. Detection of the synovial sarcoma translocation t(X;18) (SYT;SSX) in paraffin-embedded tissues using reverse transcriptase-polymerase chain reaction: a reliable and powerful diagnostic tool for pathologists. A molecular analysis of 221 mesenchymal tumors fixed in different fixatives. Human Pathol 2001;32:105-112.

⁷ Hasegawa, T., Yokoyama, R., Matsuno, Y., Shimoda, T., Hirohashi, S. Prognostic significance of histologic grade and nuclear expression of beta-catenin in synovial sarcoma. Human Pathol 2001;32:257-263.

⁸ Diagnostic Immunohistochemistry edited by Professor D. J. Dabbs, page 60.

⁹ Pelmus, M., Guillou, L., Hostein, I., Sierankowski, G., Lussan, C. and Coindre, J.M. Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. Am J Surg Pathol 2002;26:1434-40.

¹⁰ Chu, P. G. and L. M. Weiss (2002). "Keratin expression in human tissues and neoplasms." Histopathology 40(5): 403-39. (Summary data from multiple papers)

¹¹ Lopes, J. M., J. M. Nesland, et al. (2002). "Differential Ki67 and bcl-2 immunoexpression in solid-glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin." Histopathology 40(5): 464-71.

¹² Inagaki, H., T. Nagasaka, et al. (2000). "Association of SYT-SSX fusion types with proliferative activity and prognosis in synovial sarcoma." Mod Pathol 13(5): 482-8.

¹³ dos Santos, N. R., D. R. de Bruijn, et al. (2001). "Molecular mechanisms underlying human synovial sarcoma development." Genes Chromosomes Cancer 30(1): 1-14.

¹⁴ Nilsson, G., B. Skytting, et al. (1999). "The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome." Cancer Res 59(13): 3180-4.

¹⁵ Amble FR, Olsen KD, Nascimento AG,Foote RL. Head and neck synovial cell sarcoma. Otolaryngol Head Neck Surg 1992; 107:631-7

¹⁶ Argani P, Faria PA, Epstein JI, et al. Primary renal synovial sarcoma: molecular and morphologic delineation of an entity previously included among embryonal sarcomas of the kidney. Am J Surg Pathol 2000; 24:1087-96

¹⁷ Fetsch JF,Meis JM. Synovial sarcoma of the abdominal wall. Cancer 1993; 72:469-77

¹⁸ Grayson W, Nayler SJ,Jena GP. Synovial sarcoma of the parotid gland. A case report with clinicopathological analysis and review of the literature. S Afr J Surg 1998; 36:32-4; discussion 34-5

¹⁹ Iwasaki H, Ishiguro M, Ohjimi Y, et al. Synovial sarcoma of the prostate with t(X;18)(p11.2;q11.2). Am J Surg Pathol 1999; 23:220-6

²⁰ Kim DH, Sohn JH, Lee MC, et al. Primary synovial sarcoma of the kidney. Am J Surg Pathol 2000; 24:1097-104

²¹ Nielsen GP, Shaw PA, Rosenberg AE, Dickersin GR, Young RH,Scully RE. Synovial sarcoma of the vulva: a report of two cases. Mod Pathol 1996; 9:970-4

²² Ratnatunga N, Goodlad JR, Sankarakumaran N, Seimon R, Nagendran S,Fletcher CD. Primary biphasic synovial sarcoma of the orbit. J Clin Pathol 1992; 45:265-7

²³ Shmookler BM, Enzinger FM,Brannon RB. Orofacial synovial sarcoma: a clinicopathologic study of 11 new cases and review of the literature. Cancer 1982; 50:269-76

²⁴ Suster S,Moran CA. Primary synovial sarcomas of the mediastinum: a clinicopathologic, immunohistochemical, and ultrastructural study of 15 cases. Am J Surg Pathol 2005; 29:569-78

²⁵ Kleinschmidt-DeMasters BK, Mierau GW, Sze CI, et al. Unusual dural and skull-based mesenchymal neoplasms: a report of four cases. Hum Pathol 1998; 29:240-5

²⁶ Helliwell TR, King AP, Raraty M, et al. Biphasic synovial sarcoma in the small intestinal mesentery. Cancer 1995; 75:2862-6

²⁷ Miyashita T, Imamura T, Ishikawa Y, et al. Primary retroperitoneal synovial sarcoma. Intern Med 1994; 33:692-6

²⁸ Shmookler BM Retroperitoneal synovial sarcoma. A report of four cases. Am J Clin Pathol 1982; 77:686-91

²⁹ Pan CC,Chang YH. Primary synovial sarcoma of the prostate. Histopathology 2006; 48:321-3

This page last revised 27.6.2005.

©SMUHT/PW Bishop