|Year : 2019 | Volume
| Issue : 1 | Page : 29-34
Primary Pulmonary Synovial Sarcoma: Is it Worth All the Hard Work?
Sanjeev Singhal1, Deepak K Prajapat1, Rahul K Sharma2, Deepak Talwar2
1 Respiratory Medicine, Metro Centre for Respiratory Diseases, Metro Multi Specialty Hospital, Noida, Uttar Pradesh, India
2 Pulmonary and Critical Care Medicine, Metro Centre for Respiratory Diseases, Metro Multi Specialty Hospital, Noida, Uttar Pradesh, India
|Date of Web Publication||18-Jan-2019|
Deepak K Prajapat
Metro Centre for Respiratory Diseases, Metro Multi Specialty Hospital, Sector 11, Noida, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Synovial sarcoma (SS) is highly malignant tumor that occurs mainly in adolescents and young adults and is usually seen in the extremities. However, primary SS arising from the lung is extremely rare, accounting for 0.3% to 1.3%. Primary pulmonary SS (PPSS) is an extremely aggressive malignant tumor that can invade adjacent organs or give distant metastases. Besides clinical evaluation and imaging methods for definitive diagnosis, immunohistochemical examination is must. We report a case of elderly male with left lung mass lesion invading into the pericardium and left-sided pleural effusion with a history of smoking. Positron emission tomography (PET)–computerised tomography (CT)-guided trucut biopsy from lung mass lesion led to the diagnosis, and thoracoscopic pleural biopsy showed the pleural involvement with final diagnosis of PPSS (monophasic type). There are no guidelines for optimal treatment due to the rarity of such tumors. Current treatment includes resectional surgery and adjuvant chemotherapy and/or radiotherapy. But because of advanced age and poor performance status, our patient was not candidate for any treatment but palliation.
Keywords: Cytogenetic testing, immunohistochemistry, pleurodesis, spindle-cell tumor, synovial sarcoma
|How to cite this article:|
Singhal S, Prajapat DK, Sharma RK, Talwar D. Primary Pulmonary Synovial Sarcoma: Is it Worth All the Hard Work?. J Assoc Chest Physicians 2019;7:29-34
|How to cite this URL:|
Singhal S, Prajapat DK, Sharma RK, Talwar D. Primary Pulmonary Synovial Sarcoma: Is it Worth All the Hard Work?. J Assoc Chest Physicians [serial online] 2019 [cited 2019 Jun 20];7:29-34. Available from: http://www.jacpjournal.org/text.asp?2019/7/1/29/250470
| Introduction|| |
Primary synovial sarcoma (SS) arising from the lung is extremely rare, accounting for 0.3% to 1.3%, among all primary lung malignancies. SS occurs mainly in adolescents and young adults and is usually seen in the extremities. Primary pulmonary SS (PPSS) may arise in the lung, pleura, chest wall, mediastinum, or heart. It arises from primitive mesenchymal cells which undergo epithelial (and not synovial) differentiation. Histologically, this could be monophasic (consisting of spindle cells), biphasic (consisting of spindle and epithelial cells), and poorly differentiated.
| Case|| |
An 84-year-old man, reformed smoker, post-PTCA (percutaneous trans thoracic coronary angioplasty), hypertensive, and with chronic renal failure, was admitted with complaint of left-sided chest pain (nonradiating and nontender) and shortness of breath (mMRC-4, modified medical research council) for 20 days. There is history of cough, loss of appetite, and weight loss for last 2 months. There was no significant family history. Physical examination revealed heart rate (HR)—114/min, Respiratory rate (RR)—32/min, Blood pressure (BP)—100/68 mmHg, with diminished breath sounds on left side. His blood investigations at presentation revealed hemoglobin of 12.2 g/dl, total leukocyte counts of 12,500 cells/μl, and platelet counts of 260,000/μl. His serum electrolytes and liver function tests were within normal range. His kidney function test revealed urea of 92 mg/dl and creatinine of 2.75. The chest X-ray showed left costophrenic angle blunting with mediastinal widening. Noncontrast computed tomographic (NCCT) scan revealed large hypodense mass lesion of 14.2 × 7.4 × 6.4 cm3 in left upper lobe extending up to chest wall and invading the pericardium and main pulmonary artery with hypodense nodules in left lower lobe with left-sided moderate pleural effusion [[Figure 1]a and b]. Ultrasonography (USG)-guided thoracocentesis was performed which revealed hemorrhagic in color with 80% lymphocytes, protein—5.26 g/dl, lactate dehydrogenase (LDH)—251 U/l, adenosine deaminase—12 U/l with atypical mesothelial proliferation. Next day, patient developed anuria which required multiple sessions of hemodialysis. After stabilization, computerised tomography (CT)-guided trucut biopsy from the left upper lobe (LUL) mass lesion was performed. Histopathological examination showed spindle-cell tumor with fascicular arrangement of tumor cells, individual cells showed hyperchromatic nuclei with inconspicuous nucleoli, with mitosis and necrosis [[Figure 2]a,b,c and d]. The differential diagnosis narrowed to carcinoid sarcoma, SS, sarcomatoid mesothelioma, solitary fibrous tumor, and fibrosarcoma. Further, immunohistochemistry demonstrated strong positivity for cytokeratin [[Figure 3]b], vimentin [[Figure 3]a], B-cell lymphoma-2 (Bcl-2) [[Figure 3]d], CD99 [[Figure 3]c], focal positivity for epithelial membrane antigen (EMA), CD3/20, and negative for left coronary artery (LCA), CD34, smooth muscle antigen (SMA), thyroid transcription factor 1 (TTF1), and S-100. Germ-cell tumor markers such as LDH, alpha-fetoprotein (AFP), and human chorionic gonadotropin (beta HCG) levels were within normal limits. Histopathology examination (HPE) and immunohistochemistry (IHC) confirmed the diagnosis of monophasic SS of lung. Positron emission tomography (PET)–CT showed soft tissue heterogamous mass lesion in left upper lobe (10.3 × 10.2 × 8.7 cm3) of standardized uptake value (SUVmax) 15 which infiltrated mediastinum and was abutting the pericardium and main pulmonary artery. Multiple nodules also noted in left lower lobe (SUVmax 5.3) with pleural deposit posteriorly along with increased pleural effusion on left side (SUVmax 9.8) [[Figure 4]a–d].
|Figure 1 Chest xray (CXR) showing left side pleural effusion with mediastinal widening (a). NCCT chest showing large hypodense mass lesion (14.2 × 7.4 × 6.4 cm3) in left upper lobe mass lesion extending up to chest wall and invading the pericardium and main pulmonary artery with left side pleural effusion (b–d)|
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|Figure 2 (a–d) PET–CT showing soft tissue heterogamous mass lesion in left upper lobe (10.3 × 10.2 × 8.7 cm3) of SUVmax 15, infiltrating mediastinum, abutting the pericardium, and main pulmonary artery with pleural deposit posteriorly along with pleural effusion on left side (SUVmax 9.8)|
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|Figure 3 Trucut biopsy of lung on histopathological examination (HPE) with H&E stain showing spindle-cell tumor with fascicular arrangement of tumor cells. Individual cells showing hyperchromatic nuclei, inconspicuous nucleolar (pleomorphism and mitosis with necrosis) (a and b). Pleural biopsy on HPE with H&E stain showing mesothelial proliferation and foci of atypical spindle cell proliferation (c)|
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|Figure 4 (a–d) Immunohistochemistry showing high positivity for vimentin, cytokeratin, CD99, and Bcl-2|
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In view of respiratory distress and moderate pleural effusion, medical thoracoscopic intercostal drain (ICD) was put to drain fluid and obtain pleural biopsy followed by talc pleurodesis. Pleural biopsy revealed atypical spindle-cell proliferation on HPE and IHC confirmed involvement of pleura by SS [[Figure 2]c]. Considering poor performance status, advanced age, and after discussion with the family members, only palliative care was offered to the patient. Molecular testing was negative for synovial tumor (SYT) translocation. Postpleurodesis, patient was discharged in stable condition in actively mobilized state. But after 20 days, the patient was readmitted in respiratory distress with SpO2 of 83% on room air. Chest xray (CXR) showed moderate pleural effusion on left side again. This time pleurx catheter was inserted, and the patient was on oxygen support.
| Discussion|| |
SS is a misnomer as it does not arise from synovium but resembles synovium on light microscopy. It is an uncommon spindle-cell tumor accounting for 2.5% to 10% of all sarcomas and seen commonly in young people with involvement near the joints of extremities. Primary intrathoracic involvement of sarcomas is rare (0.01% of all intrathoracic malignancies). PPSS is an extremely rare malignant tumor, which is increasingly recognized as a subtype of sarcoma because of characteristic immunohistochemistry and recent identification of a distinctive chromosomal translocation specific to SS. PPSS demonstrates more aggressive clinical behavior than those originating from pleura, mediastinum, or the chest wall. PPSS chiefly affects young and middle-aged adults with no sex predilection and mostly nonsmokers. These tumors are mostly centrally located and frequently cause respiratory symptoms with effusion secondary to invasion of pleura, also seen in our case.
Imaging characteristics are mostly nonspecific and can be shared by many other tumors, for example, carcinoid sarcoma, primitive neuroectodermal tumor, thymoma, malignant mesothelioma, lymphoma, solitary fibrous tumor, fibrosarcoma, germ-cell tumor, rhabdomyosarcoma, leiomyosarcoma, etc. Apart from extent of disease and involvement of other sites, CT/PET imaging does not help to narrow the differential diagnosis. However, lymph nodes are rarely involved, and all PPSS tumors despite having well-circumscribed margins were heterogeneous with internal necrosis. Triple attenuation has been appreciated in contrast enhanced CT scans on account of calcification being reported in 50%. Heterogeneous nature of these tumors was not appreciated on NCCT scan in our case but seen on PET–CT scans. Final diagnosis is achieved through histological and immunohistochemistry analysis and may also include cytogenetic testing.
SS in general is named for their histologic pattern based on the prominence of either epithelioid or spindled-cell types. They are divided into four histologic cell types: biphasic, monophasic fibrous, monophasic epithelial, and poorly differentiated. Monophasic subtype can be mixed up with other types of sarcoma, and therefore, immunohistochemistry is essential for differential diagnosis. Our case showed spindle-cell tumor with fascicular arrangement of tumor cells, individual cells showed hyperchromatic nuclei with inconspicuous nucleoli, with mitosis and necrosis. Ancillary immunohistochemical technique helped us to reach the final diagnosis. It has been recently suggested that vimentin, cytokeratin, and EMA in combination with CD34 negativity are the most useful and sensitive protein biomarkers for the diagnosis of monophasic fibrous SS and poorly differentiated SS. In our case, immunostaining was strongly positive for vimentin, Bcl-2, CD99, and focally for cytokeratin. Negative lymphoma markers (CD45, CD20, CD31, CD5, CD30, Tdt, and CD43) and markers for germ-cell tumor (PLAP, AFP, HCG) led to exclusion of these important differentials. Negativity of S-100 protein excluded malignant peripheral nerve sheath tumor and negative SMA excluded leiomyosarcoma, and p63 was also negative, which ruled out thymoma. Solitary fibrous tumors were too ruled out because of negative CD34. Bcl-2 was positive in our case, finally clinching the diagnosis of SS of lung and diagnosis of it being primary from the lung was also based on the absence of the tumor at any other site of the body on whole body PET imaging.
Diagnostic specificity of SS is increased by cytogenetic testing but is not essential. 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, SSX1 and SSX2 in the region xp11 is seen in PPSS. Molecular testing was negative in our case, but characteristic histological and immunohistochemical findings led to the diagnosis. Of the nearly 60 cases reported in the literature, only 11 had definitive molecular detection of SYT–SSX fusion gene transcription, whereas of another study involving 14 cases of PPSS, only six has genetic translocation. However, positive SSX1 is associated with much worse survival vs. SSX2 with 5-year survival rates being 42% vs. 89%, respectively.,Surgical resection with clear resection margins is the main modality of treatment for intrathoracic SS, including those arising in the mediastinum or lung if it’s resectable. In fact, the ability to completely resect the mass is the most important factor associated with long-term survival.
For patients presenting with unresectable mediastinal or lung SSs, very limited data exist regarding the optimal therapy that can effectively downsize the tumor to resectable state. In our patient, tumor was unresectable because of large tumor mass with pericardium and pulmonary artery invasion and metastasis to pleura. Our patient was also with poor performance status and associated with multiple comorbidities and only advised palliative pleurodesis on account of rapidly refilling effusion.
We are reporting a rare case of 84-year-old male, which is very unusual age for presentation of PPSS and is highly aggressive tumor with extension into mediastinum as well as pleura, in which even pleurodesis failed which is considered as palliative treatment in such cases. Immunohistochemistry is essential to confirm the diagnosis as cytogenetic testing may be negative.
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