Rare monophasic mediastinal pleural synovial sarcoma diagnosed via endobronchial ultrasound-transbronchial needle aspiration

Abstract

The mediastinum is a rare site for occurrence of a primary synovial sarcoma (SS) with very few cases reported in the literature. The diagnosis so far has been achieved mainly via open surgery, with only three reported cases diagnosed via endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), however, none of those were located at the posterior mediastinum, without showing any oesophageal or endobronchial involvement. To our knowledge, this is the first reported case of a monophasic primary pleural mediastinal SS purely involving the posterior mediastinum without oesophageal or endobronchial component, diagnosed via EBUS-TBNA.

Background

Synovial sarcomas (SS) are rare tumours of unknown histogenesis, commonly affecting the lower extremities of young adults and the primary presentation in the mediastinum is exceedingly uncommon. After a thorough literature search using relevant keywords, very few cases of primary anterior mediastinal origin have been published. To date, only three cases were diagnosed by using endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) where all stated either oesophageal or endobronchial/lung parenchymal involvement.^1–5

Case presentation

A 75-year-old ex-smoker (60 pack-years), with reported asbestos exposure, was initially investigated by cardiologists for chest pain and leg oedema. His echocardiogram showed normal biventricular function with mild mitral regurgitation, without evidence of pulmonary hypertension. His lung function tests showed forced expiratory volume in 1 s 72% (1.75Lt), forced vital capacity 79% (2.54Lt), ratio of 93, total lung capacity 69%, residual volume 71%, carbon monoxide transfer capacity 64% and carbon monoxide transfer coefficient 98%. Subsequent chest radiograph (CxR) showed widening of the superior mediastinum with new right paratracheal shadowing and pleural plaques. His only complaint was a moderate retrosternal and subscapular pain on mobilisation, ongoing for 3–4 months, without any breathlessness on exertion or abdominal symptoms. His WHO performance status was 0 (fully independent performance without limitation in physical activities) and he did not report weight loss, fatigue, cough, haemoptysis or dysphagia. A previous CxR performed 2 years ago only showed pleural plaques.

Investigations

An urgent contrast enhanced CT scan of chest, abdomen and pelvis was organised (figure 1) and revealed a large posterior mediastinal tumour of 102×64×78 mm in overall dimensions, with confluent ipsilateral mediastinal adenopathy. Medially there was contact with the posterior tracheal wall and oesophageal wall, although with no proximal dilatation of the oesophagus. The lesion was extending posteriorly into the extrapleural right costo-vertebral tissues, with erosion of the posterior aspects of the right fourth and fifth ribs. Superiorly, the apical pleura was involved, with further erosion of the right second rib posteriorly. No other lung lesions or adenopathy identified elsewhere in the chest or in the lower neck, axillae or below the diaphragm, apart from some discrete calcified pleural plaques indicating exposure to asbestos. There was no pleural fluid on either side or disease identified below the diaphragm or other extrathoracic metastasis.

Figure 1.

Cross-sectional imaging, soft tissue configuration. Posterior pleural mediastinal mass, eroding the ribs, and in contact with, but without invasion of, trachea and oesophagus. Pleural plaques also seen, without pleural effusions.

After written informed consent, an endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) was performed as day-case procedure, under sedation (intravenous Midazolam 3 mg and Alfentanil 750 µg), using the thin Olympus EBUS scope, and size 19G needle. There was no endobronchial lesion and no obvious mucosal abnormality of the tracheal wall. Ultrasonographic examination of the tumour showed an area of necrosis (abnormal elastography) with minimal vascularity and blurred margins. Multiple passes attempted (×6) through the posterior tracheal wall with the 19G needle, avoiding the vessels, obtaining adequate tissue from the tumour. The procedure took 24 min with uneventful and rapid recovery before the patient was discharged an hour later. An esophagogastroduodenoscopy was performed a few days later and it did not show any intraluminal lesion or mucosal abnormality of the oesophagus, only external compression without obstruction or need for intervention, which explains the absence of upper gastrointestinal symptoms.

Differential diagnosis

In view of the patient’s age, imaging findings, smoking history and asbestos exposure, our differential diagnoses included primary lung cancer and mesothelioma. The initial histopathology report had pieces of tumour comprising spindle and plump cells set in variable collagenous stroma. The cellularity was also variable, with hypocellular areas seen adjacent to more cellular areas where ‘storiform’ growth pattern was noted.

Immunohistochemistry of the tumour sample highlighted positivity for CD-34 and BCL-2. Cytokeratin CK AE 1/3 and CK 8/18 were also positive. Epithelial membrane antigen, high molecular weight cytokeratin (HMWCK) (34beta-E12), CK 5/6, calretinin, S100, desmin and actin, were all negative. The pathologists’ first opinion based on the appearance of this sample was a differential between sarcomatoid carcinoma and solitary fibrous tumour, however, a more extensive immunochemistry panel and a second opinion from a centre of excellence was sought, given the unusual imaging appearance of the tumour.

The second opinion, on further testing performed on the same sample, as well as the imaging and background history, extended the list of suspected differential diagnoses to inflammatory myofibroblastic tumour, metaplastic thymoma (less likely), malignant peripheral nerve sheath tumour, solitary fibrous tumour (signal transducer and activator of transcription (STAT)-6 negative), leiomyosarcoma and mesothelioma.

Outcome and follow-up

Eventually, the fluorescence in situ hybridisation (FISH) conducted revealed that there was SS18 (SYT) locus rearrangement (figure 2), sealing the diagnosis of a primary SS and the patient was referred to the regional sarcoma multi-disciplinary team meeting (MDT) for further specialist opinion. Surgical resection was not feasible given the size and location of the tumour, and the patient was referred for chemotherapy.

Figure 2.

Fluorescence in situ hybridisation using Vysis SS18 probe demonstrating hybridisation across SS18 (SYT) locus consistent with diagnosis of synovial sarcoma.

Discussion

SS is a malignant mesenchymal tumour with variable epithelial differentiation and it often involves soft tissues of the extremities. Mediastinum can be a host for a certain number of tumours ranging from lymphoma, thymoma to some metastatic carcinomas, but the chance of it to be the primary site of SS is very low. It accounts for 2.5% to 10% of all soft-tissue sarcomas⁶ and the common presenting signs were cough, chest pain and dyspnoea.⁷

Radiographically, it tends to manifest as heterogeneously enhancing soft tissue mass with well-defined margin and necrotic, cystic or haemorrhagic changes grossly. Contralateral mediastinal shift and ipsilateral pleural effusion are reported in 33.3% and 57.1% of cases as additional findings.⁷

In terms of morphological features, SS are divided into monophasic and biphasic subtypes. The biphasic variant consists of proliferation of bland looking spindle-shaped cells, along with evidence of epithelial differentiation. Monophasic subtypes on the other hand as a majority can show either spindle cells only or occasionally epithelial components only.

The availability of molecular genetic identification (FISH or PCR) of the t(X;18) has improved diagnostic specificity as this translocation is found in over 90% of SS⁸ and the subtranscript variants may have prognostic significance. The translocation involves the SYT gene on chromosome 18 and either the SSX1 or SSX2 gene on the X chromosome.⁸

A number of case series highlighted the use of immunohistochemistry in avoiding misdiagnosis. A case series of 11 patients with pulmonary SS by Okamoto et al⁹ analysed clinicopathological features including immunohistochemical and genetical profiles. All cases were confirmed as tumour-specific SYT-SSX fusion gene before the study and showed at least focal immunohistochemical positivity for AE1/AE3, CAM5.2 and/or epithelial membrane antigen with high-proliferating cell nuclear antigen labelling index in 80% of cases. SYT-SSX1 and SYT-SSX2 fusion gene transcripts were detected in nine and two cases, respectively. Another immunohistochemical case study by Hartel et al¹⁰ showed focal positive membranous or cytoplasmic staining for epithelial markers including pancytokeratin as 100%, cytokeratin 7 (60%), epithelial membrane antigen and cytokeratin in the remaining. No tumours showed immunoreactivity for more than two cytokeratin markers. Diffuse or focal immunoreactivity was seen with CD99, Bcl-2, CD56 and smooth muscle actin.

Differential diagnosis includes malignant mesothelioma, primary lung cancer, solitary fibrous tumour and other rare primary mesenchymal sarcomas. The final diagnosis is usually achieved by the combination of radiology findings, histological methods and molecular techniques as early as possible after other alternative diagnoses were excluded.

Primary pleuropulmonary and mediastinal SS is known to be a more aggressive disease than other soft tissue counterparts. Prognostic survival can be guarded for 2 months¹¹ but with aggressive multimodal therapy, survival up to 14 years has been reported. Age (better in young patients), tumour size (<5 cm), mitotic rate (<10/10 high power fields (HPF)), FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) Staging (low grade), status of the surgical margins (negative), and SS18-SSX type (SS18-SSX2) were reported to be associated with better survival in soft tissue sarcomas.^{12 13} Complete surgical resection remains the major influencing factor in estimation of survival where adjuvant radiotherapy or chemotherapy can be used depending on the extent and location of the tumour itself. Receiving tissue biopsy can facilitate the accurate staging before considering the modality of appropriate treatment. This case highlights the usefulness and efficacy of EBUS-TBNA even in rare posterior mediastinal tumours in achieving a good tissue sample size adequate enough for extensive tests.

Learning points.

• Posterior mediastinal synovial sarcomas can remain silent for a long time without always causing upper gastrointestinal symptoms.

• A broader range of differential diagnoses should be considered, in combination with good application of immunohistochemistry in dealing with unusual presentations of mediastinal tumours.

• Endobronchial ultrasound with transbronchial needle aspiration can be safely used in an effort to confirm the diagnosis in such rare challenging cases, without any compromise in diagnostic yield or ability to do further complex testing on the obtained sample size.