Intrathoracic synovial sarcoma

Synovial sarcoma most commonly occurs at a primary site in soft tissues of the extremities, with subsequent lung metastases. Primary intrathoracic synovial sarcoma is rare. Most cases involve the lung¹⁰ and pleura⁴, with a few that are mediastinal^12,16 or involve the chest wall¹³, oesophagus¹⁵ or heart^7,14. To make the diagnosis of a primary intrathoracic synovial sarcoma, a soft tissue primary should be excluded.

Epidemiology

This is a tumour of predominantly of adults, with a wide age range (mean 48 years) and an equal sex distribution¹ or male predominance¹². Childhood cases have been reported^11,12. Biphasic tumours possibly occur in younger patients^4,6,12.

Clinical features

 Patients present with dyspnea, pleural effusion, haemoptysis, pneumothorax, chest pain or cough, or an incidental finding on chest x-ray^1,2. A few patients have constitutional symptoms of fever, weight loss or weakness¹².

Radiology

Mediastinal cases may be anterior or posterior¹². The mass may be well defined or ill-defined¹². There may be focal calcification¹². Pulmonary cases may present with multiple nodules¹².

Macroscopic appearances

The tumour most often forms a circumscribed mass which is white to grey with foci of haemorrhage, necrosis and cyst formation¹². There may be gross invasion of pleura, pericardium, heart, great vessels, ribs, chest wall or vertebrae¹². Extension into the cardiac ventricles may be polypoidal¹². Some cases grow in a diffuse plaque-like manner, resembling mesothelioma⁴.

Histopathology

Most cases are monophasic^{1,2,3,5,10,12} or poorly differentiated^1,3, less often biphasic^1,4,6,12,16; the FNCLCC grade is 2 or 3¹.

The sarcomatous component consists of areas of densely packed fusiform cells alternating with loose myxoid areas². Fascicles may form a herringbone or storiform pattern¹². There may be foci of round epithelioid cells, as seen in poorly differentiated synovial sarcoma. Vascularity is prominent¹². There are areas of thick intercellular collagen¹². Mitotic counts range to over 20 per 10 HPF. Myxoid change and calcification may occur. Mucins are positive for PAS⁴.

Biphasic cases show an epithelial component of very variable extent¹². The glandular component may show cytoplasmic clearing¹².

Immunohistochemistry

Synovial sarcoma is characterised by positivity for EMA and cytokeratins in combination with negativity for CD34.

	AE1/AE3	23/39 (cases were poorly differentiated or monophasic)1, 4/5 (focal positivity)2, 11/12 (at least focal positivity)3, 7/11 (focal positivity)9
	EMA	35/391, 2/5 (focal positivity)2, 5/54, 8/11 (1 case diffuse, 1 case moderate, others focal positivity)9, 25/25 (strong focal positivity)10, 1/1 (focal positivity)11
	AE1/AE3 or EMA	36/391, 11/11 (or Cam5.2)9
	AE1/AE3 and EMA	26/391
	Cam5.2	8/11 (focal positivity)9
	polyclonal anticytokeratin	5/5 (spindle cell component also positive in 4 cases)4
	Positive with at least one of broad spectrum anticytokeratin, Cam5.2 and EMA	15/15 (glandular component positive with all three epithelial markers in the five biphasic cases)12
	BerEP4	5/5 (spindle cell component also positive in 4 cases)4
	CEA	3/5 (spindle cell component also positive in 4 cases)4
	S100	3/391, 2/5 (epithelial and spindle cell components positive)4, 9/11 (varying extent)9, 0/2510, 1/1 (focal positivity)11
	SMA	5/391
	h-caldesmon	0/371
	bcl-2	29/341, 3/38, 8/11 (varying extent)9, 10/10 (in all cases, more than 80% of the spindle cells were strongly positive)12
	CD99	27/351, 1/4 (focal positivity)2, 3/38, 3/5 (moderate or diffuse)9, 8/10 (focal to diffuse positivity)12
	Calretinin	5/391, 62/103
	E-cadherin	1/9 (reduced expression in the one case more than focally positive)9
	aberrant cytoplasmic b-catenin	6/99
	CD117	3/381
	CerbB-2	6/151
	EGFR	8/151
	vimentin	5/5 (epithelial component positive in 2 cases)4, 25/25 (strong diffuse positivity)10, 1/1 (diffuse positivity)11
	SMA	0/119, 0/2510, 0/1012
	HHF-35	0/1012
	Desmin	0/119, 0/2510, 0/1012
	HMB45	0/1012
	CD30	0/1012
	CD31	0/1012
	CD34	3/391, 0/42, 0/1012

Some pulmonary cases appear to include glandular structures, but the positivity of these for TTF-1 shows that they are entrapped lung tissue¹.

Ultrastructure

Cells are oval to spindle with closed apposed cell membranes, poorly formed desmosomes and abundant intermediate filaments¹².

Cytogenetics

The presence of the translocation t(X;18) leading to fusion of SYT (at 18q11) with SSX1, SSX2 or SSX4 (all at Xp11) has been used as the defining characteristic in a major study of intrathoracic synovial sarcomas¹. In the largest series, 21 of 38 showed t(X;18)(SYT-SSX1), the other 17 showing t(X;18)(SYT-SSX1)¹.

Differential diagnosis

Biphasic tumours give a differential including:

• metastatic carcinoma: the glands show more cytological atypia than in synovial sarcoma. A spindle cell component is usually absent.

• pulmonary blastoma: usually an intrapulmonary lesion. The glandular cells have clear cytoplasm, resembling fetal lung. There are often morules of round basaloid stromal cells at the base of the glands.

• thymic carcinosarcoma: the spindle cell component does not stain for cytokeratins. The glandular component is more overtly malignant than in synovial sarcoma.

• biphasic mesothelioma: extends diffusely along the pleura.

The monophasic sarcomatoid and poorly differentiated synovial sarcomas pose the greatest diagnostic challenge:

• sarcomatoid carcinoma: shows greater pleomorphism. Less likely to be positive for bcl-2 and CD99.

• sarcomatoid mesothelioma: fascicles are short and blunt. There is negativity for BerEP4 and CEA. PAS-positive mucin is absent. One study has specifically compared synovial sarcoma (mainly of the extremities) with mesothelioma.

• solitary fibrous tumour:: tumours are often pedunculated. There is collagen deposition between the cells. The cells are positive for CD34 and CD99 , negative for EMA and cytokeratins, negative for t(X;18) translocation².

• spindle cell thymoma: mitotic figures are lacking. bcl-2 and CD99 are negative. Cytokeratin positivity is more diffuse than is usual in synovial sarcoma.

• spindle cell thymic carcinoma: likely to be negative for bcl-2 and CD99.

• pleuropulmonary blastoma: occurs in children and adolescents. There are multiple peripheral cysts. Blastematous cells and heterologous elements are present.

• MPNST: note that up to 30% of synovial sarcomas are positive for S-100¹².

• fibrosarcoma

• angiosarcoma

• leiomyosarcoma

• Ewing's/PNET

Treatment

Resection if possible. If not (fully) resectable, radiotherapy¹².

Prognosis

Metastases may occur to lymph nodes, lung, liver or epidural space¹². Intrathoracic synovial sarcomas are more aggressive than those of the extremity⁹, probably due to the difficulty of obtaining complete resection. Median metastasis-free survival is 43 months¹, with two and five year survivals of 65% and 32% respectively.

References

¹ Begueret H, Galateau-Salle F, Guillou L, et al. Primary intrathoracic synovial sarcoma: a clinicopathologic study of 40 t(X;18)-positive cases from the French Sarcoma Group and the Mesopath Group. Am J Surg Pathol 2005; 29:339-46

² Aubry MC, Bridge JA, Wickert R,Tazelaar HD Primary monophasic synovial sarcoma of the pleura: five cases confirmed by the presence of SYT-SSX fusion transcript. Am J Surg Pathol 2001; 25:776-81

³ Essary LR, Vargas SO,Fletcher CD Primary pleuropulmonary synovial sarcoma: reappraisal of a recently described anatomic subset. Cancer 2002; 94:459-69

⁴ Gaertner E, Zeren EH, Fleming MV, Colby TV,Travis WD Biphasic synovial sarcomas arising in the pleural cavity. A clinicopathologic study of five cases. Am J Surg Pathol 1996; 20:36-45

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; 34:205-10

⁶ Jawahar DA, Vuletin JC, Gorecki P, Persechino F, Macera M,Magazeh P Primary biphasic synovial sarcoma of the pleura. Respir Med 1997; 91:568-70

⁷ Nicholson AG, Rigby M, Lincoln C, Meller S,Fisher C. Synovial sarcoma of the heart. Histopathology 1997; 30:349-52

⁸ Nicholson AG, Goldstraw P,Fisher C Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases. Histopathology 1998; 33:508-13

⁹ Okamoto S, Hisaoka M, Daa T, Hatakeyama K, Iwamasa T,Hashimoto H Primary pulmonary synovial sarcoma: a clinicopathologic, immunohistochemical, and molecular study of 11 cases. Hum Pathol 2004; 35:850-6

¹⁰ Zeren H, Moran CA, Suster S, Fishback NF,Koss MN Primary pulmonary sarcomas with features of monophasic synovial sarcoma: a clinicopathological, immunohistochemical, and ultrastructural study of 25 cases. Hum Pathol 1995; 26:474-80

¹¹ Kaplan MA, Goodman MD, Satish J, et al. Primary pulmonary sarcoma with morphologic features of monophasic synovial sarcoma and chromosome translocation t(X; 18). Am J Clin Pathol 1996; 105:195-9

¹² 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

¹³ Fujimoto K, Hashimoto S, Abe T, et al. Synovial sarcoma arising from the chest wall: MR imaging findings. Radiat Med 1997; 15:411-4

¹⁴ Iyengar V, Lineberger AS, Kerman S, et al. Synovial sarcoma of the heart. Correlation with cytogenetic findings. Arch Pathol Lab Med 1995; 119:1080-2

¹⁵ Anton-Pacheco J, Cano I, Cuadros J, et al. Synovial sarcoma of the esophagus. J Pediatr Surg 1996; 31:1703-5

¹⁶ Witkin GB, Miettinen M,Rosai J A biphasic tumor of the mediastinum with features of synovial sarcoma. A report of four cases. Am J Surg Pathol 1989; 13:490-9

This page last revised 25.3.2005.

©SMUHT/PW Bishop