The Oncologist, Vol. 9, No. 3, 339–342,
June 2004
© 2004 AlphaMed Press
Primary Pulmonary Synovial Sarcoma: A Case Report and Review of Current Diagnostic and Therapeutic Standards
Sheri Dennison,
Eric Weppler,
George Giacoppe
Department of Internal Medicine, Madigan Army Medical Center, Tacoma, Washington, USA
Correspondence: Sheri Dennison, M.D., Department of Internal Medicine, Madigan Army Medical Center, Tacoma, Washington 98431-0001, USA. Telephone: 253-967-7523; Fax: 253-967-4013; e-mail: sheri.dennison{at}nw.amedd.army.mil
 |
LEARNING OBJECTIVES
|
|---|
After completing this course, the reader will be able to:
- Describe primary pulmonary synovial sarcoma as a rare tumor that usually arises in young adults as a large pleural-based intrathoracic mass.
- Explain that the diagnosis is made by histology, immunohistochemical studies, and, more recently, by identification of the SYT-SSX1 or SYT-SSX2 chromosomal translocations.
- List factors that portend a worse prognosis, including inability to achieve a complete resection, larger tumor size, male sex, older age, high-grade tumor with necrosis, and the SYT-SSX1 variant.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
|
ABSTRACT
|
|---|
A 30-year-old female presented with hemoptysis, chest pain, and a rapidly enlarging pleural-based mass, and was found to have primary synovial sarcoma of the lung. Primary pulmonary sarcomas comprise <1% of all primary lung malignancies. They present clinically in young adults with cough, chest pain, shortness of breath, or hemoptysis, with a mass on x-ray and computerized tomography scan. Diagnosis is made by histology and immunohistochemistry. Histologic diagnosis has recently been supplemented by cytogenetic analysis, which offers important prognostic information. The mainstay of treatment remains complete surgical excision. Prognosis is poor, with an overall 5-year survival rate of 50%.
Key Words. Sarcoma • Malignancy • Pleura • Synovial • Genetics
|
CASE
|
|---|
A 30-year-old Filipino-American female presented to the emergency department with hemoptysis and left-sided chest pain. The patient had experienced a mild cough and left-sided chest pain for 3 months. She awoke the morning of admission with severe chest pain and several episodes of hemoptysis, each with approximately 30 ml of bright red blood.
Her past medical history was unremarkable. She had no previous surgeries. She did not smoke or drink alcohol. She had no family history of cancer. She had spent the previous year in Korea; she had a negative purified protein derivative 6 months prior to admission. On a review of systems, she was in excellent health and had no symptoms other than the cough and chest pain. The physical exam was remarkable only for slight tachypnea and absent breath sounds in the left lung field.
A chest x-ray in the emergency department showed a large left apical lung mass, which was measured by computerized tomography (CT) at 11 cm x 8 cm (Fig. 1
). There was no adenopathy. Bronchoscopy showed slow bleeding from the left upper bronchial division, but no endobronchial lesion. She was admitted to the intensive care unit for monitoring, and cardiothoracic surgery was consulted.
View larger version (135K):
[in this window]
[in a new window]
|
Figure 1. Chest x-ray on presentation to the emergency department demonstrating a well-defined mass in the left upper lobe.
|
|
A records review revealed an emergency department visit 3 months earlier for a mild cough and chest pain. The chest x-ray done at that time showed, in retrospect, a 2 cm x 3 cm pleural-based lesion in the left upper lobe.
At thoracotomy, the mass proved to have little solid component, being comprised of a large cavity within the left upper lobe filled with hematoma and white caseous material, arising from the pleura, and adherent to the chest wall. A left upper lobectomy, partial chest wall resection, and muscle flap reconstruction were performed. The patient was extubated on the second postoperative day and recovered without complications.
The pathologic specimen consisted of the left upper lobe attached to the chest wall by a 3.5-cm area of tissue resembling thickened pleura and the resected ribs (Fig. 2). Inside the lobe was a cavity measuring 10.5 cm x 8.7 cm x 2.8 cm, which opened to the thickened pleura. Histology showed a spindle and epithelioid malignant neoplasm composed of densely packed cells with frequent mitotic figures, suggesting a sarcoma (Fig. 3). Immunohistochemical (IHC) staining was negative for cytokeratin and epithelial membrane antigen (EMA), positive for vimentin and bcl-2, and focally positive for calretinin. A reverse transcriptase-polymerase chain reaction assay identified the t(x:18) translocation with the SYT-SSX1 variant, confirming the diagnosis of synovial sarcoma.
View larger version (86K):
[in this window]
[in a new window]
|
Figure 2. Gross specimen. Tumor and cavity are visible, with adjacent left upper lobe and portions of ribs.
|
|
View larger version (168K):
[in this window]
[in a new window]
|
Figure 3. Hematoxylin-eosin stained section of tumor at medium power (x40) showing a spindle and epithelioid pattern with frequent mitotic figures, suggesting a sarcoma.
|
|
|
DISCUSSION
|
|---|
Synovial sarcoma accounts for approximately 8% of soft tissue sarcomas. It is not derived from the synovium, but from immature mesenchymal elements. It typically presents in adolescents and young adults, most commonly in the soft tissues of the extremities, especially near large joints, but head and neck, lung, heart, mediastinum, and abdominal wall sites have been reported. Synovial sarcoma arising from the pleura has rarely been reported [1]. Pulmonary sarcomas overall are very uncommon and comprise only 0.5% of all primary lung malignancies.
In the few reported cases of primary synovial sarcomas of the lung, patients have presented with chest wall pain, cough, shortness of breath, or hemoptysis. The average age at presentation is 25 years. All patients had large pleural-based intrathoracic masses at presentation. Intraoperatively, necrosis and hemorrhage were almost uniformly present [2].
Pleural-based synovial sarcomas must be differentiated from other primary pulmonary neoplasms, such as malignant fibrous histiocytomas, malignant mesotheliomas, adenocarcinomas, and carcinosarcomas. Extrathoracic primary tumors should be excluded by physical exam and CT. Malignant fibrous histiocytoma and synovial sarcoma are the most common variants of pulmonary sarcoma.
Synovial sarcomas in general are named for their histologic pattern based on the prominence of either epithelioid or spindled cell types. They are divided into four histologic types: biphasic, monophasic fibrous, monophasic epithelial, and poorly differentiated. The case reported here showed a predominantly fibrous biphasic pattern of densely packed spindled and epithelioid cells with increased nuclear to cytoplasmic ratios with prominent nucleoli. Mitotic activity was brisk.
Histology is often supplemented with IHC studies. Immunohistochemically, synovial sarcomas are nearly uniformly positive for cytokeratin, EMA, bcl-2, and vimentin, and negative for S-100, desmin, smooth muscle actin, and vascular tumor markers (Table 1) [3]. IHC studies in this case were unusual in that they were negative for cytokeratin and EMA and positive for bcl-2, vimentin, and, focally, for calretinin.
Histology and IHC have been supplemented recently by cytogenetic analyses, which can confirm the diagnosis of synovial sarcoma. Cytogenetic studies of synovial sarcomas have revealed the chromosomal translocation t(x;18)(p11;q11). This translocation fuses the SYT gene from chromosome 18 to either of two homologous genes at Xp11, SSX1 or SSX2. SYT-SSX1 and SYT-SSX2 are thought to function as aberrant transcription regulators. The sensitivity of this test for diagnostic purposes approaches 100%. In one study, the SSX1 variant was detected in 64% and the SSX2 variant was detected in 36% of 45 synovial sarcomas. Most biphasic tumors have been found to have an SYT-SSX1 fusion transcript, and most monophasic tumors have an SYT-SSX2 transcript. The prognosis for patients with the SYT-SSX2 abnormality is better (no deaths in the first 5 years after surgery in one study group) than the prognosis for patients with the SYT-SSX1 abnormality [4]. A second study noted the 5-year metastasis-free survival rate for patients with the SYT-SSX1 variant to be 42%, compared with 89% for patients with the SYT-SSX2 variant [5]. In the case presented here, cytokeratin and EMA stains were negative, but the translocation t(X;18) and the SYT-SSX1 variant were present, confirming the diagnosis.
The prognosis for patients with pulmonary synovial sarcoma is poor, with an overall 5-year survival rate of 50%. Factors predicting a worse prognosis for patients with synovial sarcomas include tumor size (>5 cm), male gender, older age (>20 years), extensive tumor necrosis, high grade, large number of mitotic figures (>10 per 10 high-powered fields), neurovascular invasion, and, recently, the SYT-SSX1 variant [6]. The main prognostic factor is the ability to achieve a complete resection. There is no standardized therapy; most patients are treated with surgery or with surgery and adjuvant radiation therapy. The rarity of this tumor has not permitted controlled studies of adjuvant chemotherapy. Synovial sarcomas are chemosensitive to ifosfamide and doxorubicin, with an overall response rate of approximately 24% [7]. In a meta-analysis, adjuvant chemotherapy for sarcomas improved the time to local recurrence and recurrence-free survival rate, with a trend toward a better overall survival rate.
|
REFERENCES
|
|---|
- Keel SB, Bacha E, Mark EJ et al. Primary pulmonary sarcoma: a clinicopathologic study of 26 cases. Mod Pathol 1999;12:1124–1131.[Medline]
- Gaertner E, Zeren EJ, Fleming MV et al. Biphasic synovial sarcomas arising in the pleural cavity: a clinicopathologic study of five cases. Am J Surg Pathol 1996;20:36–45.[CrossRef][Medline]
- Weiss S, Goldblum J. Enzinger and Weiss’s Soft Tissue Tumors, Fourth Edition. St. Louis, MO: Mosby, 2001:1502–1504.
- Kawai A, Woodruff J, Healey JH et al. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 1998;338:153–160.[Abstract/Free Full Text]
- Nilsson G, Skytting B, Xie Y et al. The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res 1999;59:3180–3184.[Abstract/Free Full Text]
- Trassard M, Le Doussal V, Hacene K et al. Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. J Clin Oncol 2001;19:525–534.[Abstract/Free Full Text]
- Spillane AJ, A’Hern R, Judson IR et al. Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol 2000;18:3794–3803.[Abstract/Free Full Text]
Received August 4, 2003;
accepted for publication December 16, 2003.
Top
Learning Objectives
Abstract
