Primary pleuropulmonary synovial sarcoma presenting with recurrent spontaneous pneumothorax

Abstract

Primary pleuropulmonary synovial sarcoma (PPSS) is a rare mesenchymal neoplasm, accounting for less than 0.5% of all primary lung tumours. Presentation is often vague and may include cough, chest pain or dyspnoea. Due to the tumour’s rarity, diagnosis can be challenging, and not much is known about the disease process or optimal treatment course. In this case report, we describe an older female patient who underwent blebectomy for recurrent pneumothorax. No masses or suspected lesions were found on CT imaging besides the bleb. The bleb was then found to be PPSS via RT-PCR cytology. This case aims to increase awareness of malignant tumours clinically presenting as recurrent pneumothorax with no discrete lung mass on CT imaging. We also highlight the importance of cytogenetics to confirm the diagnosis of this rare tumour.

Background

Synovial sarcoma (SS) is a rare mesenchymal tumour that is commonly seen in young adults with a median age of 35 years. The tumour typically arises in deep soft tissue near large joints.¹ Lung is a very unusual primary location for this tumour.² Here, we report an older female patient who presented with recurrent pneumothorax and a lung bleb that was found to be primary pleuropulmonary SS (PPSS) by RT-PCR.

Case presentation

A woman in her 60s, with no prior smoking history, presented with a spontaneous left-sided pneumothorax that resolved after a chest tube placement. CT scan at the time showed posterior left subpleural pneumatocele versus loculated pneumothorax with mild peripheral nodularity (figure 1). The finding was deemed benign and patient was discharged with plan for repeat imaging in a year. She was doing well up until a year later when she presented again with dyspnoea, and chest pain and was found to have a recurrent left-sided pneumothorax. Symptoms again resolved with a chest tube. CT chest did not reveal any mass or suspected lesion except for a small bleb in the left lower lobe (figure 2). Her recurrent spontaneous pneumothorax was attributed to the bleb, hence patient underwent a video-assisted thoracoscopic surgery (VATS) wedge resection of the bleb as well as a mechanical pleurodesis. Pathology revealed a biphasic SS (figure 3), CD99, epithelial membrane antigen (EMA), transducin-like enhancer of split 1 (TLE1) and B cell lymphoma 2 (BCL-2) were positive. Resected specimen showed that margins were involved by tumour. Positron emission tomography scan did not show evidence of metastatic disease. RT-PCR showed SS18-SSX2 fusion, which established the final diagnosis of lung primary SS, stage 1.

Figure 1.

CT scan at initial presentation showing posterior left subpleural pneumatocele vs loculated pneumothorax (circle): (A) axial view, (B) coronal view and (C) sagittal view.

Figure 2.

Repeat CT scan a year after initial presentation redemonstrating the small left-sided lung bleb (circle): (A) axial view, (B) coronal view and (C) sagittal view.

Figure 3.

Immunohistochemistry with H&E staining showed a mixture of well differentiated spindle cell and epithelial cell, suggesting biphasic subtype of synovial sarcoma: (A) low power and (B) high power.

Outcome and follow-up

Due to the R1 wedge resection, patient underwent definitive left VATS lower lobectomy with pleural adhesiolysis. Level 11 lymph node was also removed and was negative for malignancy. Patient did not receive any adjuvant chemotherapy or radiation. She was doing well at subsequent clinic visits. Surveillance radiograph at 3-year follow-up showed no evidence of disease.

Discussion

SS mainly affects young adults and accounts for about 5%–10% of all sarcoma cases. The term is a misnomer, as SS virtually never arises from the synovium. Instead, it is often found near large joints of the extremities. Its exact origin is not well established and lacks immunohistochemistry (IHC) evidence that links it to normal synovium.^{1 3} SS can arise from a variety of anatomical locations, including limbs, head and neck, and the trunk. Lung is a very rare primary location for SS.² Patients typically present with vague pulmonary symptoms such as shortness of breath, chest pain and cough. Recurrent pneumothorax or hemoptysis is a much rare clinical presentation. Imaging often shows a well-defined mass with associated ipsilateral pleural effusion but no lymphadenopathy.⁴ Our patient was much older than the expected age range with unusual clinical picture at presentation. Her CT imaging also did not show any mass or suspected lesion besides a small bleb.

Histologically, SS exhibits a wide range of morphological spectrum and can be classified into four main subtypes: poorly differentiated, biphasic, monophasic fibrous and monophasic epithelial. The classification depends on the predominant cell type of either spindle cell, epithelial cell or both.⁵ IHC staining is important for diagnosis. Markers such as cytokeratins, EMA, TLE1, BCL-2 and vimentin are often positive in PPSS, while desmin and S100 are often negative.^{1 6} Among the markers, EMA is the most useful with reported sensitivity of 91% and specificity of 82%.⁷ TLE1 is not specific to PPSS, but has a very high sensitivity of 97%, effectively ruling out the tumour if negative.¹ BCL-2, an antiapoptotic protein, is another useful biomarker with sensitivity of 87% and specificity of 70%.⁷ BCL-2 has been studied as a potential therapeutic target for SS, given its overexpression in this tumour. However, in preclinical models, treatment of SS with venetoclax (a selective BCL-2 inhibitor) has so far been ineffective.⁸ Our patient’s pathology sample demonstrated a mixture of both well-differentiated spindle cell and epithelial cell, rendering it biphasic subtype of PPSS.

Molecular testing is gold standard for diagnosing PPSS. Genetically, PPSS is similar to extrathoracic soft tissue SS and is characterised by translocation t(X;18) (p11.2;q11.2), resulting in fusion of SYT gene (also called SS18) on chromosome 18 with either SSX1 or SSX2 gene on chromosome X. The SS18-SSX translocation is present in more than 90% of SS cases, regardless of morphologic subtype, making it an essential tool in confirming the diagnosis.⁹ An FISH, RT-PCR or next-generation sequencing can be employed to detect this fusion gene. Recently, a novel approach with IHC stain using SS18-SSX fusion-specific antibody was developed and theoretically could replace traditional molecular genetic and cytogenetic testing in most SS cases.¹⁰ The fusion involving SSX2 may be a predictor of better prognosis compared with SSX1. A study reported median and 5-year overall survivals for the SS18-SSX1 type was 6.1 years and 53% compared with 13.7 years and 73% for SS18-SSX2 fusion type (p=0.03). Overall survival was not affected by age, sex or morphologic subtype. The study also concluded that for patients with early disease stages at diagnosis, SS18-SSX fusion type was the most significant prognostic factor.¹¹ Further research is needed to fully investigate its utility in assessing prognosis.

PPSS is a very aggressive tumour, with late metastasis found in more than 50% of cases at 5-year follow-up. The tumour has a wide range of 5-year survival rate, estimated between 24% and 76%.¹² Factors such as metastatic disease at diagnosis, high-grade histology, large tumour size (>5 cm), truncal lesions and absence of wide resection are often associated with worse outcome. Although there is no gold standard for management of PPSS, surgical resection remains the mainstay therapy for non-metastatic disease. Neoadjuvant or adjuvant chemotherapy may be helpful depending on the case. SS is often chemosensitive and treatment with anthracycline alone or in combination with ifosfamide is typically used in high-risk cases. Our patient did not receive adjuvant chemotherapy after her definitive lobectomy as she had a low-grade tumour confined to the left lower lung lobe. She continued to follow-up with clinic for active surveillance and remained disease free at 3-year mark.

Learning points.

• Primary pleuropulmonary synovial sarcoma (PPSS) often presents with non-specific pulmonary symptoms such as dyspnoea, cough or chest pain. Spontaneous recurrent pneumothorax is a rare presentation but should prompt further investigation for malignancy.

• Typical imaging findings including well-defined mass with associated ipsilateral pleural effusion may be absent.

• Molecular confirmation with RT-PCR, FISH or next-generation sequencing is gold standard for diagnosing PPSS. Immunohistochemistry staining with SS18-SSX fusion-specific antibody may serve as an alternative to cytogenetics.

• PPSS is a highly aggressive but chemosensitive tumour. Anthracycline alone or in combination with ifosfamide may be beneficial in addition to surgical resection for high-risk cases.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).