Primary synovial sarcoma of the lung: a rare presentation, diagnostic dilemma and review of literature

Abstract

Primary synovial sarcoma of the lung (PSSL) is a rare tumour with only 0.5% incidence among other primary malignant lung tumours. Published medical literature regarding the natural history treatment protocol and clinical outcomes of PSSL remains limited. Here, we present a case of a 39-year-old man with primary synovial sarcoma with long-term follow-up, which was initially viewed as a metastasis from another unknown site. After evaluating histopathologically from the specimen post left lung metastasectomy and ruling out any other site for neoplastic changes, the diagnosis of PSSL was confirmed. Furthermore, this article reviews the literature and discusses various aspects of PSSL, including clinical presentation, radiological imaging and pathological characteristics, diagnostic dilemma, management and prognosis. This paper serves to provide an update and aims to enhance the understanding of PSSL. Timely diagnosis and treatment are imperative to achieve improved outcomes.

Background

Primary synovial sarcoma (PSS) is a mesenchymal tumour seen mainly in adolescents and young adults and usually arises from periarticular tissue.¹ The lung is an extremely unusual site of PSS and accounts for only 0.5% of all lung malignancies whereas lung secondaries from a primary extrapulmonary sarcoma are more common.^{1 2} Other primaries, including pleura, chest wall, and mediastinum or heart, are rarely reported sites.¹ Here we report a case of primary synovial sarcoma of the lung (PSSL) in a 39-year-old man and diagnostic dilemmas during the management.

Case presentation

A 39-year-old man presented to an outside hospital with complaints of a single episode of blood in sputum, breathlessness on exertion and occasional dry cough, for which a contrast-enhanced CT (CECT) scan was done. It revealed a large homogeneous mass lesion in the left lingular lobe of the lung, leading to suspicion of neoplastic aetiology. CT-guided biopsy showed fibrinous material and a few round cells. To rule out metastasis the patient underwent a whole-body positron emission tomography (PET) CT scan which revealed a 3.5 × 3.7 cm well-defined heterogeneous mass lesion of standardised uptake value (SUV) max 3.7 in the lingular segment of the left lung. No mediastinal, hilar adenopathy (figure 1) or distant metastasis was detected. Left lung metastasectomy at an outside hospital was done, presuming it to be an isolated single site metastasis from an unknown primary.

Figure 1.

Positron emission tomography (PET)-CT showing soft tissue heterogamous mass lesion in the lingular segment of the left lung (3.5 cm × 3.7 cm) of standardised uptake value (SUV) max 3.7.

Postop histopathology showed a cellular tumour with short-spindled to rounded cells, and pale nuclei, with short fascicles. It didn't reveal any biphasic pattern and the tumour cells had a fairly monotonous appearance. Mitotic count was 10/10 high-power field (HPF). Necrosis was seen in <50% of sampled sections with focal calcifications. There was a sprinkling of mast cells in the lesion. Lymphovascular or perineural invasion was absent. A section from grossly unremarkable adjacent lung tissue showed microscopic tumour deposits. The pleural and parenchymal cut margins were free. Federation Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) Score: Differentiation Score (2) + Necrosis Score (1) + Mitotic Score (2)=5 = grade 2.

Immunohistochemistry (IHC) showed patchy expression of epithelial membrane antigen (EMA), vimentin, CD99 (cluster of differentiation) and B cell lymphoma 2 (BCL-2) were all widely positive, and transducine-like enhancer of split 1 (TLE1) was strongly expressed in practically all the tumour nuclei. Integrase interactor-1(INI1) was retained weakly in the nuclei while S100, smooth muscle anctin (SMA), desmin, H-caldesmon, cytokeratin moll’s number (CK-MNF) and human melanoma black-45 (HMB45) were all negative. Final histopathological diagnosis was made as monophasic synovial sarcoma with FNCLCC grade 2, metastatic to lower lobe of the left lung and pleura (figure 2). The histopathological reports were reviewed and the diagnosis was revised to primary monophasic synovial sarcoma of the lung because of no FDG uptake at any other site.

Figure 2.

(A) A highly cellular tumour showing circumscription. Uninvolved lung parenchyma is identified in the lower left corner. (B) Higher magnification of the tumour (200 ×, H&E stain) shows sheets of tumour cells having high N:C ratio. (C) Strong staining with TLE-1. (D) Tumour cells also showing moderate intensity of staining with CD 99. (E) Peripheral part of the tumour shows staining with pancytokeratin. (F) Peripheral part of the tumour shows staining with epithelial membrane antigen (EMA). (G) Diffuse cytoplasmic staining is seen with BCL-2. (H) No staining seen with CD34. (I) ki-67 labelling index in the highest proliferating areas is 20%–25%.

The patient was advised adjuvant treatment but defaulted and visited our hospital 6 months postsurgery. Slides and blocks reviewed at our centre showed malignant mesenchymal tumour. Fluorescence in situ hybridisation (FISH) analysis for rearrangement of the SS18 (SYT) gene on chromosome 18q11.2 was advised to confirm the diagnosis, which was positive (93%) (figure 3).

Figure 3.

Cell showing one green, one orange and one green-orange (fusion) signal indicating positive for SYT gene rearrangement.

Outcome and follow-up

A repeat whole-body PET-CECT scan revealed postsurgical changes only. There was no evidence of metabolically active lesion anywhere else in the body. The patient’s case was discussed at the multidisciplinary tumour board and it was decided to closely follow-up the patient because of R0 resection, prolonged time gap for adjuvant radiotherapy postsurgery (around 4 months) and a repeat PET-CT showing no residual/recurrent disease.

Currently, the patient has been regularly followed up for 2 years postsurgery and is disease-free on clinical examination and follow-up PET-CT scans.

Discussion

PSS is a rare, aggressive, malignant mesenchymal tumour accounting for 2.5%–10% of all sarcomas and is most commonly seen in the deep soft tissues of the extremities, especially near large joints.^{1 3} Synovial sarcoma is a misnomer as it arises from primitive pluripotent mesenchymal cells and not the synovium, but it resembles the synovial architecture under a light microscope.³

To the best of our knowledge around 61 cases of synovial sarcoma of the lung have been reported to date in the English literature.⁴ Due to its rarity, diagnosis of PSSL and exclusion of metastatic sarcoma of the lung depends on several factors such as clinical presentation, radiological findings, histopathological features, IHC and cytogenetic parameter.

Mostly PSSL tumours are centrally located and a majority are reported in non-smokers, and young and middle-aged adults with no sex predilection.³ Patients usually present with symptoms of postobstructive pneumonia, that is, cough, dyspnoea and haemoptysis. Peripheral tumours are less common and initially asymptomatic but they can infiltrate the adjacent organs, and present with chest pain, pleural or pericardial effusions, haemothorax and recurrent pneumothorax.⁵ The present case is also a non-smoker adult man who presented with a single episode of haemoptysis, breathlessness on exertion, and dry cough.

Imaging characteristics are mostly non-specific and can be shared by many other tumours which add to the diagnostic dilemma. On CT examination these tumours have heterogeneous well-circumscribed margins with internal necrosis; however, lymph nodes are rarely involved. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging also does not help to narrow the differential diagnosis apart from defining the extent of disease and metastasis to other sites.⁴ In our case PET-CT scan showed FDG avid mass lesion in the lingular segment of the left lung without any evidence of distant metastasis.

Histologically these synovial sarcomas are mainly composed of two morphologically different types of cells that is, epithelial cells or fibroblast-like spindle cells and are classified into four types: biphasic, poorly differentiated, monophasic fibrous type (spindle cell) and monophasic epithelial type. The monophasic subtype needs to be differentiated from fibrosarcoma, haemangiopericytoma and leiomyosarcoma, the spindle cell variant from squamous cell carcinoma.⁶ In our case histopathology showed cellular tumour with short spindled to rounded cells with pale nuclei. There was no biphasic pattern and the tumour cells had a fairly monotonous appearance with mitosis, necrosis and focal calcifications. Lymphovascular or perineural invasion was absent.

A monophasic subtype can be mixed up with other types of sarcoma, and therefore, IHC is essential for differential diagnosis. Immunohistochemically, PSS is usually positive for cytokeratin, EMA, BCL-2, vimentin and negative for S-100, desmin.⁷ IHC, in this case, showed patchy expression of EMA and vimentin, CD99, BCL-2, TLE1 were also widely positive while INI1 was retained weakly in the nuclei but S100, Desmin, H-caldesmon, CK (MNF), HMB45 were negative.

The diagnostic specificity of PSS is increased by cytogenetic testing but is not essential.⁸ Reciprocal chromosomal translocation (X;18)(p11.2; q11.2), which results from the fusion of the SYT gene on chromosome 18 to either of two genes, synovial sarcoma X-1 (SSX1) and synovial sarcoma X-2 (SSX2) in the region xp11 is seen in PSS.⁸ In our patient, FISH analysis was performed to confirm the diagnosis which showed that the rearrangement of SS18 (SYT) gene on chromosome 18q11.2 was positive (93%).

Due to the rare incidence of PSSL, initially, a clinical diagnosis of metastatic disease from an undetected primary site was made. The primary histopathological report also mentioned metastatic sarcoma from other sites, but after reviewing the slides, clinical presentation, imaging data, and findings from the chromosomal analysis, PSSL of the lung was diagnosed finally.

Surgery is the mainstay of therapy and free surgical margins are critical for prevention of local recurrence. However, these tumours are highly aggressive with an often large size already at presentation, therefore, it is difficult to achieve tumor-free surgical margins.⁹ In our case, the patient was treated for a secondary malignant mesenchymal tumour of the lung from an unknown origin in the beginning and gross excision of the tumour was done. Despite the large size of the tumour, R0 resection was achieved but looking at the aggressive nature of the disease, adjuvant treatment was advised. Inadvertent delay by the patient in reporting for adjuvant treatment precluded any further treatment, and the patient is doing well without any adjuvant treatment.

Neoadjuvant and adjuvant chemotherapy may be required, as synovial sarcoma is considered to be a relatively chemosensitive tumour and treatment with adriamycin alone or in combination with ifosfamide remains the standard chemotherapy in such metastatic disease.¹⁰ This again was not an option in this case for the reason mentioned above.

Prognostic factors includes age >20 years, female sex, R1 or R2 resection, tumour size >5 cm, extensive tumour necrosis, a high number of mitoses (10/10 HPF), neurovascular invasion, and recently, SYT–SSX1 variant. The SYT–SSX1 variant is indicative of poor prognosis. Specifically, positive SSX1 is associated with much worse survival as compared with SSX2 with 5-year survival rates being 42% vs 89%, respectively.⁴ Our patient, aged 39 years, with a mitotic count 10/10HPF, and positive for reciprocal chromosomal translocation (X; 18) (p11.2; q11.2), was expected to perform poorly but contrary to the available evidence is doing fine with definitive surgery only.

Learning points.

• Primary synovial sarcoma of the lung is a very rare variant of sarcoma with little available data and management guidelines.

• It is an aggressive tumour requiring fluorescence in situ hybridisation to demonstrate reciprocal chromosomal translocation (X; 18) (p11.2; q11.2) for conformation of diagnosis besides complete evaluation including history and examination, radiological assessments, histopathology and IHC.

• Treatment is extrapolated from other sarcoma treatment protocols due to lack of data. Management is usually multimodal in nature and surgical excision, wherever feasible, is the primary treatment with adjuvant treatments having limited scope.