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 mediastinal12,16 or involve the chest wall13, oesophagus15 or heart7,14. 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 reported11,12. Biphasic tumours possibly occur in younger patients4,6,12.

Clinical features

 Patients present with dyspnea, pleural effusion, haemoptysis, pneumothorax, chest pain or cough, or an incidental finding on chest x-ray1,2. 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 monophasic1,2,3,5,10,12 or poorly differentiated1,3, less often biphasic1,4,6,12,16; 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.

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