ARTICLE IN PRESS doi:10.1510/icvts.2009.213934
Interactive CardioVascular and Thoracic Surgery 9 (2009) 1026–1028 www.icvts.org
Case report - Thoracic oncologic
Primary synovial sarcoma of the lung as an incidental finding夞 Stefan B. Watzkaa,b,*, Ulrike Setinekc, Helmut Proschd, Michael R. Mu ¨llera,b Division of Thoracic Surgery, Otto Wagner Hospital, Sanatoriumstraße 2, 1140 Vienna, Austria b Karl Landsteiner Institute for Thoracic Oncology, Otto Wagner Hospital, Vienna, Austria c Division of Pathology, Otto Wagner Hospital, Vienna, Austria d Division of Radiology, Otto Wagner Hospital, Vienna, Austria
a
Received 5 June 2009; received in revised form 15 August 2009; accepted 7 September 2009
Abstract Synovial sarcoma of the lung (SSL) is a very rare but aggressive primary lung tumor. Due to its unusual histological features, it can easily be misdiagnosed, if only small biopsies of the tumor are investigated. Here, we review two recent cases of SSL diagnosed and treated in our institution. The first case is a 37-year-old male with a round nodule in the right lower lobe; he underwent a lobectomy. Histologically, the nodule resembled a biphasic tumor. Cytogenetic analysis revealed a translocation t (X; 18), and the diagnosis of primary SSL could be established. The patient is alive and disease-free since 45 months following surgery. The second case is a 41-year-old male with a cystic lesion in the right lower lobe, removed by video-assisted thoracic surgery (VATS) segmentectomy. In the tumor tissue, spindle cell-rich and cystic structures could be found, together with epithelial elements. Because the tumor contained also a translocation t (X; 18), it could be diagnosed as monophasic SSL. The patient is alive and disease-free since 11 months. Since rare diseases of the lung may present as subtle and focal changes, complete removal of suspect pulmonary lesions is always advisable. 䊚 2009 Published by European Association for Cardio-Thoracic Surgery. All rights reserved. Keywords: Lung; Neoplastic disease; Mesenchymal tumor; Histology; Chromosomal translocation
1. Introduction Pulmonary sarcomas are uncommon and comprise about 0.5% of all lung malignancies w1x. Malignant fibrous histiocytoma and primary synovial sarcoma (SSL) are the most common variants of pulmonary sarcoma. Due to its unusual histological features, showing often only focal changes within an epithelial-like nodule of sometimes even benign appearance, primary synovial sarcoma can easily be misdiagnosed. This is particularly the case, if only small biopsies of the tumor are investigated. Here, we review two incidental cases of primary synovial sarcoma in our institution. 2. Material and methods We conducted a retrospective case analysis with special emphasis on clinical follow-up and on histopathological features. 3. Results 3.1. Patient 1 A 37-year-old asymptomatic Caucasian male presented with a well-circumscribed round nodule of 1.5 cm diameter 夞 Presented at the 17th European Conference on General Thoracic Surgery, Krakow, Poland, May 31–June 3, 2009. *Corresponding author. Tel.: q431 91060-44008; fax: q431 4023570. E-mail address:
[email protected] (S.B. Watzka). 䊚 2009 Published by European Association for Cardio-Thoracic Surgery
in the right lower lobe detected incidentally in a chest CTscan. His medical history was uneventful, but he was a heavy smoker (30 pack-years). For establishment of a definitive diagnosis, he underwent a diagnostic thoracotomy. As frozen section analysis proved malignancy, a right lower lobe lobectomy including en-bloc mediastinal lymph node dissection was performed. Postoperative course was uneventful, and the patient could be discharged on day 8 after operation. Histologically, the nodule showed a complex architecture. Besides the presence of a spindle cell component, microcystic cavities lined by monomorphic cubic cells without cilia could be identified. In between the spindle cells and the microcysts, we found a dense capillary network. Resection margins were negative. In the immunohistochemical work-up, the spindle cell component was positive for vimentin, epithelial membrane antigen (EMA), neural cell adhesion molecule (N-CAM), synaptophysin, and neuronspecific enolase (NSE), and negative for cytokeratins; the cubic cell lining was positive for thyroid transcription factor-1 (TTF1), cytokeratins, and EMA, and negative for neuroendocrine markers. Thus, the investigated nodule was classified as a highly vascularized lung tumor with a spindle cell, neuroendocrine, and cystic component, but with unclear dignity. Finally, a translocation analysis has been performed, which showed the characteristic translocation
ARTICLE IN PRESS S.B. Watzka et al. / Interactive CardioVascular and Thoracic Surgery 9 (2009) 1026–1028
Work in Progress Report Protocol Institutional Report ESCVS Article Proposal for Bailout Procedure Negative Results Follow-up Paper State-of-the-art Best Evidence Topic Nomenclature
A 41-year-old, asymptomatic Caucasian male presented with a cystic lesion of 4 cm diameter and of unclear dignity in the right lower lobe (Fig. 1). He was a mild smoker (5 pack-years). Seventeen years before, the patient had been diagnosed with seminoma, which had been treated by surgery and adjuvant chemotherapy. Eleven months before, during the regular follow-up, the pulmonary lesion was discovered in a chest CT-scan. He had then a transbronchial biopsy, which showed a vimentin-positive spindle cell proliferation; assessment of dignity was not possible in the scarce biopsy material. Regarding the seminoma, he was disease-free. The attending pulmologist chose to further observe the lesion by regular chest CT-scan. However, since the radiological morphology of the cystic lesion remained atypical, showing a solid margin towards the normal lung parenchyma, surgical removal by video-assisted thoracic surgery (VATS) segmentectomy was commenced 11 months after first diagnosis. The postoperative course was uneventful, and the patient could be discharged on day 2 after operation. Histologically, a spindle cell-rich tumor tissue with infiltrative growth pattern and containing cystic structures was found. Resection margins were negative. Immunohistochemistry was strongly positive for vimentin and bcl-2, but negative against all cytokeratins besides EMA. From the neuroendcrine marker panel, only N-CAM was positive (Fig. 2). Because of the morphology and the inconclusive staining pattern, the slides were sent to a reference pathologist in Austria, who classified the histological findings as intrapulmonary thymoma of type A. This interpretation was contradicted by a German reference pathologist, who proposed the diagnosis of a biphasic synovial sarcoma because of the co-expression of vimentin and EMA with bcl-2. A final consultation with a multinational reference center for pulmonary pathology in the USA, which detected a translocation t (X; 18), resulted in the diagnosis of a monophasic SSL. The patient is alive and disease-free without any further treatment since 11 months after surgery.
Primary synovial sarcoma is a rare and aggressive primary neoplasm of the lung. It has first been described in 1995 by Zeren and co-workers as a distinctive primary sarcoma of the lung, however, sharing histological and immunohistochemical features with the monophasic synovial sarcoma of soft tissue w2x. Most SSL patients in large series in the literature (summarized by Hartel et al. w3x) are presenting with chest pain, dyspnea, cough or hemoptysis. However, in our case series both patients were asymptomatic at presentation. In the radiological work-up, SSL appear mostly as well-circumscribed nodules of considerable size, but usually without involvement of nodal stations w4x. Radiologically, it is often not possible to differentiate between masses of pleural or pulmonary origin. A needle biopsy can only reveal the mesenchymal origin, but not the dignity of the process. Thus, complete removal of the nodule is mandatory. If it is a spindle cell tumor, it is important to consider synovial sarcoma as a differential diagnosis. Extrathoracic primary tumors should also be excluded by whole body CT and cranial MRI. Immunohistochemistry does not always allow an unequivocal diagnosis; most important differential diagnoses are: the fibrous pleural tumor, sarcomatoid subtype of malignant pleural mesothelioma, spindle cell carcinoma, malignant peripheral nerve sheath tumor w5x. The most important diagnostic tool is the detection of the typical translocation t (X; 18) (p11.2; q11.2) by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR), which can be found in 90% of cases w6–8x. Usually, this translocation produces a fusion transcript of the SYT gene (exon 10) on 18q and the SSX1 gene on Xp (exon 6); however, other exons (e.g. exon 9 and exon 5) can also be involved w9x. Therapy of choice is the surgical removal of the tumor with the aim to achieve negative resection margins. Com-
New Ideas
3.2. Patient 2
4. Discussion
Editorial
t (X; 18) (p11; q11), which can typically be found in primary synovial sarcoma. The patient is alive and disease-free without any further treatment since 45 months following surgery.
1027
Historical Pages Brief Case Report Communication
Fig. 1. Axial (a) and coronal (b) CT-scan of patient 2 showing a mostly thinwalled cystic lesion with a solid component at the upper aspect in the right lower lobe.
Fig. 2. (a) Overview of spindle cell tumor with densely allocated spindle cells (=200 magnification); (b) N-CAM staining of the tumor. Malignant mesothelioma, spindle cell carcinoma, and fibrous pleural tumor would not stain for N-CAM (=400 magnification); (c) vimentin and (d) cytokeratin staining show the double expression of mesenchymal and epithelial markers in the tumor (=400 magnification).
ARTICLE IN PRESS 1028
S.B. Watzka et al. / Interactive CardioVascular and Thoracic Surgery 9 (2009) 1026–1028
pleteness of resection but not size and grade is significantly associated with increased survival w10x. The role of adjuvant radiochemotherapy in SSL is unclear, since there are no randomized controlled trials. Both patients in our study did not get any adjuvant treatment, and are so far diseasefree. References w1x Martini N, Hajdu SI, Beattie EJ Jr. Primary sarcoma of the lung. J Thorac Cardiovasc Surg 1971;61:33–38. w2x 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;26:474–480. w3x Hartel PH, Fanburg-Smith JC, Frazier AA, Galvin JR, Lichy JH, Shilo K, Franks TJ. Primary pulmonary and mediastinal synovial sarcoma: a clinicopathologic study of 60 cases and comparison with five prior series. Mod Pathol 2007;20:760–769. w4x Frazier AA, Franks TJ, Pugatch RD, Galvin JR. From the archives of the AFIP: pleuropulmonary synovial sarcoma. Radiographics 2006;26:923– 940.
w5x Rdzanek M, Fresco R, Pass HI, Carbone M. Spindle cell tumors of the pleura: differential diagnosis. Semin Diagn Pathol 2006;23:44–55. w6x Fletcher CDM, Unni K, Mertens F. Pathology and genetics of tumours of soft tissue and bone. World Health Organization Classification of Tumours. Lyon, France: IARC, 2002:427. w7x Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM, Gusterson BA, Cooper CS. Identification of novel genes, SYT and SSX, involved in the t(X; 18) (p11.2; q11.2) translocation found in human synovial sarcoma. Nat Genet 1994;7:502–508. w8x Guillou L, Coindre J, Gallagher G, Terrier P, Gebhard S, de Saint Aubain Somerhausen N, Michels J, Jundt G, Vince DR, 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. Hum Pathol 2001;32:105–112. w9x Morikawa H, Tanaka T, Hamaji M, Ueno Y, Yasuda S, Kato T, Kohno Y, Toguchida J. A case of primary synovial sarcoma of the thorax with a variant SYT-SSX1 fusion transcript. Ann Thorac Surg 2009;88:297–300. w10x Bacha EA, Wright CD, Grillo HC, Wain JC, Moncure A, Keel SB, Donahue DM, Mathisen DJ. Surgical treatment of primary pulmonary sarcomas. Eur J Cardiothorac Surg 1999;15:456–460.
