Solitary primary pulmonary synovial sarcoma: A case report

INTRODUCTION

Synovial sarcoma (SS) is an uncommon and malignant soft tissue tumor that accounts for around 10% of soft tissue sarcomas[1]. Although it often arises in the limbs, particularly near the knee joints, SS has the potential to occur in any part of the body, including the head and neck, lungs, kidneys, prostate, skin,vulva, blood vessels, and nerve tissue[2]. The remarkable genetic feature of SS is the pathognomonic t(X;18)(p11;Q11) translocations, resulting in fusion of the SS18 gene, known as SYT, on chromosome 18 with one of the three highly homologous SSX genes (SSX1, SSX2, or SSX4), which are all on the Xchromosome[3,4].

While most of the synovial sarcoma in the lung is metastatic, primary pulmonary SS (PPSS) is extremely rare, especially solitary PPSS[5]. Because of a lack of specific characteristics, PPSS tends to be confused with other benign or malignant lung lesions, such as teratoma, lymphoma, spherical tuberculosis, and pulmonary cryptococcosis. In this report, we describe a case of solitary PPSS that was confirmed

positron emission tomography-computed tomography (PET-CT), histological analysis,immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) genetic testing.Additionally, we conduct a review of the clinical manifestations, diagnosis, and treatment of this type of disease using pertinent literature.

CASE PRESENTATION

Chief complaints

In August 2020, a 33-year-old male was admitted due to two years of discovered lung shadows, and intermittent coughing and hemoptysis for one month.

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History of present illness

The patient had undergone a routine chest computed tomography (CT) examination in July 2018 due to trauma, which had shown a solitary roundish nodule with a maximum diameter of approximately 14 mm and smooth edges in the upper lobe of the right lung (Figure 1A and B). The nodule was initially diagnosed as a benign lung tumor and was left untreated. In November 2019, a chest CT re-examination revealed that the lesion had grown bigger significantly, reaching approximately 30 mm in diameter,with a smooth edge and visible shallow lobes. The patient declined the suggestion of a further diagnosis by biopsy (Figure 1C and D). From July 2020, the patient exhibited intermittent coughing with white sputum and hemoptysis. The amount of hemoptysis varied from 50 to 100 mL, without accompanying chills, fever, chest tightness, wheezing, chest pain, weight loss, or night sweats. The hemoptysis became severe two days before admission, occurring dozens of times per day.

Metastatic lesions of primary SS often occur in the lungs and share similar lung imaging characteristics as PPSS. Thus, it is necessary to use an approach capable of distinguishing these two types of lesions for the determination of further treatment[13]. In this case, using the whole body PET-CT scan ruled out the possibility of extrapulmonary primary SS. PET-CT examination frequently reveals a significant increase in fluorodeoxyglucose (FDG) uptake in lung lesions, with an SUVmax ranging from 2.2 to 17.6[14]. In this case, the SUVmax value of the lesion was 5.6, which indicated that hypermetabolic activity occurred within the tumor cells.

History of past illness

The patient had not noticed any remarkable medical conditions in the past.

The enhanced chest CT revealed a significantly enlarged round mass of approximately 20 mm × 34 mm× 42 mm in the posterior segment of the right upper lobe with uneven density, distinct edge boundary,spot-like calcification, and a slightly shallow profile. Additionally, the enhanced chest CT scan revealed an uneven level of enhancement of the mass, and the mass periphery had an enhanced shadow in the shape of a ring (Figure 1E and F).

Personal and family history

The patient has no known family history of genetic diseases.

Physical examination

PPSS is an extremely rare disease with atypical clinical manifestations and imaging changes, raising the risk of diagnostic confusion with other lung diseases, which should attract attention from clinicians.Here, we excluded the potential of SS lung metastasis through systemic examination and diagnosed this case as solitary PPSS based on pathological classification using IHC measurements and the SYT gene break-apart characteristics determined with a FISH test. Later, the tumor was removed by surgical resection, which will benefit the patient’s survival and prognosis.

Laboratory examinations

The patient’s major laboratory tests, including hematological test, blood biochemical test, infection related, tumor biomarker tests and immune related were all within normal limits.

Imaging examinations

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Further diagnostic work-up

Later, the bronchoscopy procedure revealed a neoplasm at the posterior opening of the right upper lobe surrounded by purulent secretions and a small amount of bleeding. Clamp biopsy was performed due to the mass completely obstructing the airway and preventing the lens body from passing through(Figure 2E and F). H&E staining of the biopsy showed spindle-shaped malignant tumor cells, and IHC showed CKpan (-), CK8/18 (-), CK7 (-), Syn (-), TTF1 (-), P40 (-), P63 (-), CK5/6 (-), dcsmin (-), SMA (-),S-100 (-), and Ki-67 (30% +). The subsequent PET-CT whole-body scan revealed only a mass in the upper lobe of the right lung, with uneven radioactivity uptake and a standardized uptake value (SUV) max of 5.6 (Figure 2A-D).

He WW and Huang ZX acquired the medical report of the patient; Analysis and interpretation of data were performed by He WW, Huang ZX, Wang WJ, Qiu YB, Shi Y and Sun HM; Xia QY explained the histopathological results; He WW and Sun HM reviewed the Literature and drafted the paper; all authors read and approved the final paper.

FINAL DIAGNOSIS

The final diagnosis of the presented case is PPSS.

TREATMENT

Under general anesthesia, the patient underwent surgical thoracoscopic resection of the posterior segment of the right upper lobe of the lung. After the operation, the patient recovered and was discharged after declining chemotherapy.

OUTCOME AND FOLLOW-UP

The patient recovered after the operation, and six months after the operation, the follow-up chest CT examination revealed no obvious abnormality (Figure 1G and H).

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DISCUSSION

PPSS is more prevalent in young and middle-aged adults, with an average onset age of 36.5-58 years[6-10] and a male-to-female incidence ratio of 2:1[6,11]. Cough, chest pain, dyspnea, and hemoptysis are all common symptoms. In this case, the patient's primary clinical manifestations were intermittent cough and severe hemoptysis. We ruled out the potential of metastatic lesions from an extrapulmonary primary SS using a PET-CT whole-body scan. Additional H&E staining, IHC, and FISH detection of surgically resected specimens confirmed the diagnosis of PPSS.

PPSS is characterized by roundish parenchymal masses with smooth edges and inconspicuous lobes on imaging. The lesions may be accompanied by necrosis, liquefaction, calcification without cavitation,burrs, and bronchial traction. In addition, enhanced CT frequently reveals an uneven enhancement of the mass or a thick-walled ring, often associated with ipsilateral pleural effusion[12]. In this case, the chest enhanced CT revealed typical peripheral pattern changes of PPSS, including smooth edges,uneven lesion density, calcification, and ring enhancement.

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As with SS, PPSS exhibits bidirectional differentiation into mesenchymal and epithelial tissues.Monophasic fibrous and (or) epithelial cells are intertwined under the microscope to form dense tumor cell bundles, some of which are mucous. IHC helps in identifying the pathological type of SS by detecting epithelial and mesenchymal biomarkers. Machen

[15] reported that BCL-2 was expressed diffusely in 98% of SS cases and CD99 was expressed focally or diffusely in approximately 60% of cases.Consistent with these earlier studies, IHC analysis of the PPSS tissue in this case revealed increased expression of BCL-2 and CD99, as well as a significantly increased Ki-67 index of 30%.

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FISH using an SS18 break-apart probe is currently the most widely used approach to demonstrate the presumptive presence of one of the SS18-SSX fusions. If the probe breaks, it suggests that the SS18 gene and SSX gene are fused[16]. It has been reported that the sensitivity and specificity of FISH detection using the SS18 two-color fracture separation probe in the diagnosis of synovial sarcoma are 83% and 100%, respectively[17,18]. In this study, SS18 two-color break separation probe FISH technology was used to specifically detect whether the SS18 gene was broken. The use of isolated probes can cover different fusion subtypes and determine the fusion genes more comprehensively. In this case, the breaking apart of the SYT gene was detected by FISH, which confirmed the final diagnosis of SS.

PPSS has a poor overall prognosis, with a 5-year survival rate of approximately 50% to 80%. Due to the rarity of PPSS, there are no guidelines for its optimal treatment. Therefore, the treatment recommendations for SS have shifted significantly in recent years toward radical resection in conjunction with radiotherapy and/or chemotherapy[19]. At present, surgical resection remains the first line of treatment for solitary PPSS. Simultaneously, because SS is a chemotherapy-sensitive tumor[20], Adriamycin alone or in combination with Ifosfamide remains the standard chemotherapy regimen for SS. The combined approach achieves a total remission rate of approximately 50%, which is superior to any monotherapy[19]. Regrettably, the patient in this case refused postoperative chemotherapy.

CONCLUSION

Upon admission to the hospital, the patient’s initial physical examination were all within normal limits.

ACKNOWLEDGEMENTS

The authors would like to thank Dr. Yan-Wen Yao and Dr. Wei-Quan Zhu for their constructive comments on this work.

FOOTNOTES

Under general anesthesia, the patient underwent surgical thoracoscopic resection of the posterior segment of the right upper lobe of the lung. The specimen was grayish-yellow in color, covered with small multi-nodulated structures, and composed of soft tissue (Figure 2G). H&E staining of the excised specimen showed a large number of spindle-shaped malignant tumor cells (Figure 3A), and IHC indicated CD99 (3+), BCL-2 (2+), EMA (-), CD34 (-), and TLE1 (-) (Figure 3B-F). In addition, the FISH test showed the splitting of SS18, which furthermore confirmed the diagnosis of SS, pathologically classified as monophasic fibrous or spindle-cell type.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

The authors declare that they have no conflict of interest.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

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This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

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The next morning, when her father (as she had always called him) came to see her, she told him that she could give him no answer until he had presented her with a dress the colour of the sky. The king, overjoyed at this answer, sent for all the choicest weavers12 and dressmakers in the kingdom, and commanded them to make a robe the colour of the sky without an instant’s delay, or he would cut off their heads at once. Dreadfully frightened at this threat, they all began to dye and cut and sew, and in two days they brought hack13 the dress, which looked as if it had been cut straight out of the heavens! The poor girl was thunderstruck, and did not know what to do; so in the night she harnessed her sheep again, and went in search of her godmother.

China

Wei-Wei He 0000-0002-6313-2276; Zhi-Xin Huang 0000-0001-5891-3839; Wen-Jing Wang 0000-0002-0497-510X; Yu-Lei Li 0000-0001-5954-1790; Qiu-Yuan Xia 0000-0001-7201-8611; Yong-Bin Qiu 0000-0001-7318-0493; Yi Shi 0000-0003-4129-794X; Hui-Ming Sun 0000-0003-3438-6004.

Liu JH

A

Liu JH

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