A Synovial sarcoma (SS) is an uncommon mesenchymal tumour entity which accounts for 5% to 10% of soft tissue sarcomas (STS). Primary renal synovial sarcoma (PRSS) is a very rare, rapidly growing tumour, which is associated with the potential for the development of metastatic disease. The main prognostic factors of PRSS include the size of the tumour, the histopathology grade, as well as translocation t (X; 18) (p11.2; q11.2) (fusion of SYT gene -chromosome 18- with SSX genes (1, 2 or 4)-chromosome X) is recognised as the commonest pathognomonic sign. Aggressive surgical resection of the tumour with complete excision of the together with concomitant regional lymphadenectomy is the treatment of choice for majority of PRSSs, while additional en bloc resection of the adjacent affected organs is often undertaken. At the moment, the role of pre-operative or post-operative chemotherapy has remained equivocal. The prognosis of patients with PRSS has tended to be poor, as the 5-year survival rate has been documented to vary from 20% to 30% in reported cases and studies and further deterioration in the outcome pursuant to treatment has been documented in association with the pathology examination finding of a high mitotic activity. Local recurrence even after complete radical excision of the kidney tumour has remained the most frequent recurrence which eventually emanates in the development of distant metastases and death of patients.

Synovial sarcoma (SS) is stated to be a rare mesenchymal tumour entity which accounts for 5% to 10% of soft tissue sarcomas (STS) [1] [2]. Lejars and Rubens-Duval were stated to have reported and initially named the tumour as synovial endothelioma in 1919. The most predominant postulate for the origin of synovial sarcoma was iterated to related to the retrograde differentiation of an undefined mesenchymal cell [1] [3] [4]. It has been iterated that this type of tumour could be encountered either within the extremities close to articulations in about 85% to 95% of cases or bursas, sinews and the head and neck region in about 10% of cases [1] [5]. It has also been iterated that synovial sarcoma could be identified in very unusual parts of the human body without correlation to the joints, including the nervous system, thoracic and abdominal wall cavity, prostate, fallopian tubes, retroperitoneum, bones and the kidneys [1] [5] [6] [7] [8] [9]. Primary renal synovial sarcoma (PRSS) has been stated to constitute between 1% and 3% among all kidney tumours [1] [10]. It had been iterated that the first description of synovial sarcoma of the kidney was in 1999 by Faria, while it had been previously categorized as an embryonal sarcoma of the kidney [1] [11] [12]. It has been pointed out that the clinical manifesting features of PRSS had typically ranged from presence of an enlarged abdominal mass, vague pain and haematuria to local invasion as well as liver and lung metastatic disease [1] [13] [14] [15] [16] [17]. In view of the limited number reported sporadic cases and case series of PRSSs, there is so far no global consensus opinion guidelines related to the diagnosis and treatment of this uncommon tumour entity. There is therefore a global need for guidelines to be agreed upon regarding the diagnostic criteria and options of treatment for this rare aggressive tumour. [1] [18] [19] [20] [21]. Before guidelines can be made regarding the diagnostic features and management options, it would be necessary for urologists, oncologists, and pharmacotherapy research workers, radiologists and pathologists would need to study the tumour carefully and multi-disciplinary global treatment trials need to be established quickly and clinicians who treat new cases of PRSS should be encouraged to report their cases in the literature so that lessons can be learnt from their experiences. This article on synovial carcinoma of the kidney is divided into two parts (A) Overview which has discussed the general overview aspects of synovial sarcoma and (B) Miscellaneous narrations from some case reports, case series and studies on synovial sarcoma of the kidney. 

To review and update the literature on synovial sarcoma of kidney. 

Internet data bases were searched including: Google; Google Scholar; Yahoo; and PUBMED. The search words that were used included: Synovial sarcoma of kidney; Renal synovial sarcoma. Eighty-four (84) references were identified which were used to write the article which has been divided into two parts (A): Overview which has discussed general overview aspects of synovial sarcoma and (B) Miscellaneous narrations from some case reports, case series and studies on synovial sarcoma of the kidney.

[A] OVERVIEW [22] 

Definition / general statement 

• Synovial sarcoma is a terminology that is used for a malignant soft tissue tumour of uncertain histogenesis with variable epithelial differentiation [22]

Essential features [22] 

• It has been pointed out that synovial sarcoma could occur within or encompassing any tissue within the human body
• It has been iterated that multiple morphologies of synovial sarcoma exist including monophasic spindle cell, biphasic, poorly differentiated, myxoid, ossifying and monophasic epithelial
• It has been documented that synovial sarcoma comprises of monotonous spindle cells with vesicular, plump and overlapping nuclei with hemangiopericytic vessels
• It has been iterated that upon immunohistochemistry staining studies the tumour cells of synovial sarcoma exhibit positive staining for the ensuing tumour markers.:             
• TLE1+,
• cytokeratin+,
• EMA+,
• BCL2+,
• CD99+
• It has been iterated that upon molecular and cytogenetics studies synovial sarcoma does demonstrate a typifying chromosomal translocation t(X;18)(p11;q11) involving genes SS18 and either SSX1, SSX2 or SSX4

Terminology

• It has been stated that an obsolete terminology which had been used for synovial sarcoma of kidney is: malignant synovioma [22] 

Epidemiology [22] 

• It has been stated that synovial sarcoma accounts for 5% to- 10% of all soft tissue sarcomas that afflict the body.
• It has been iterated that the median age of individuals diagnosed as having synovial sarcoma at the time of the initial diagnosis is 35 years 
• It has been documented that the age range of individuals who had been diagnosed as afflicted by synovial sarcoma has varied from 0 years to more than eighty-five years (85+ years)
• It has been iterated that there is a slight male predominance in synovial sarcoma of male to female 1.2:1 [M: F = 1.2:1]
• It has been documented that 17.6% of cases of synovial sarcoma occur in children and young adults ages 0 - 19 [23] 

Sites [22] 

With regard to the sites of the human body that could be afflicted by synovial sarcoma, synovial sarcoma can occur anywhere within the body and the primary site distribution has been summated as follows: [23] 

• Extremities: 68.7%
• Trunk: 15.7%
• Head and neck: 6.3%
• Intrathoracic: 5.3%
• Intra-abdominal: 1.8%
• Other: 2.2%

Pathophysiology [22] 

• It has been iterated that the pathophysiology of synovial sarcoma is triggered by the chromosomal translocation t(X;18)(p11;q11) involving genes SS18 and either SSX1, SSX2 or SSX4
• It has been documented that translocation has multiple effects upon oncogenetic pathways, including the SWI / SNF chromatin remodelling complex, polycomb repressor complex and canonical Wnt pathway [24] 
• It has been stated that in synovial sarcoma translocation partner affects epithelial differentiation: [25] 
• SS18-SSX1: 60 - 70% monophasic, 30 - 40% biphasic
• SS18-SSX2: 97% monophasic, 3% biphasic
• SS18-SSX1 inhibits Snail gene while SS18-SSX2 inhibits Slug gene [26] 
• Interfering with Snail leads to stronger de-repression of E-cadherin than does interfering with Slug
• Stronger E-cadherin and increased extracellular matrix protein MMP2 expression are needed for biphasic morphology to develop

Aetiology [22] 

• With regard to the aetiology of synovial sarcoma, it has been pointed out that despite the name, the cells of origin of the tumour are not synovial cells
• It has been iterated that the histogenesis of synovial sarcoma has been still debated
• It has been stated that one (1) study had demonstrated stem cell marker expression in synovial sarcoma which had indicated that the that origin of synovial sarcoma may be a multipotent mesenchymal stem cell [27] 
• It has also been stated that one (1) study utilising mice had identified satellite cells (immature myoblasts) as a potential source of synovial sarcoma [28] 

Clinical features

It has been documented that synovial sarcoma is very rarely associated with previous radiotherapy [29] 

• It has been stated that synovial sarcoma is not classically known to be associated with any syndromes

Diagnosis [22]

• With regard to the diagnosis of synovial sarcoma, it has been pointed out that biopsy of the neoplasm is required for pathology examination in order for a definitive pathology diagnosis to be made.
• It has been iterated that diagnosis of synovial sarcoma is confirmed by molecular or cytogenetic testing for SS18-SSX fusion and the commonly used methods include FISH, RT-PCR and NGS. [30] [31] 

Radiology description

The radiology imaging features of synovial sarcoma had been summated as follows: [22] 

• Most synovial sarcomas present as round to oval, lobulated tumour masses
• It has been documented that bone involvement in synovial sarcoma is rare
• It has been pointed out that ossifying synovial sarcomas have typifying spotty radiopacities that are caused by focal calcifications [32] 

Prognostic factors [22] 

• Factors of poor prognostication for synovial sarcoma had been summated as follows: 
• SS18-SSX1 translocation
• Monophasic and poorly differentiated subtypes [33] 
• Male gender [34] 
• Older age at diagnosis. [35] 
• Size ≥ 5 cm [36] 
• Non-extremity location [36] 
• Deep seated tumours [37] 
• Higher percentage of tumour necrosis [38] 
• Mitotic activity ≥ 10/high power field or higher Ki67 activity [39] 
• Tumour grade based on Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) [40] 
• Immunohistochemical expression of CXCR4 and IGF1R, [41] 
• Positive surgical margins
• It has been iterated that in synovial sarcoma, H3K27me3 and VEGF expression are associated with histological grade, distant metastasis and stage [42] 
• Grading of synovial sarcoma: the grading of synovial sarcoma has been summated as follows: 
• In adults: grade based upon FNCLCC grading system
• In children: new grading system by the Paediatric Oncology Group (POG) for nonrhabdomyosarcoma soft tissue sarcoma in children showed discrepant higher grading for synovial sarcoma compared with FNCLCC

Treatment

The treatment options of synovial sarcoma had been summated as follows:

• Primarily surgical excision of the tumour tends to be the main treatment of localised tumours. 
• Radiotherapy and adjuvant chemotherapy had been evaluated in high-risk situations (including tumours that measure more than or larger than five centimetres (> 5 cm) or tumours that are difficult to resect
• Radiotherapy: it has been iterated that adjuvant radiotherapy had been demonstrated to be associated with improvement in oncological outcome and overall survival of patients who have undergone adjuvant radiotherapy for synovial sarcoma [34] 
• Adjuvant chemotherapy: summations that had been made regarding adjuvant chemotherapy for synovial sarcoma include:
• Data is conflicting on utilisation of adjuvant chemotherapy for synovial sarcoma but it can be considered in high-risk patients
• Ifosfamide was demonstrated to increase disease specific survival [43] 
• 2 large European Organization for Research and Treatment of Cancer (EORTC) database clinical trials had shown no benefit of doxorubicin on overall survival [44] 
• Novel therapies: Summations made regarding novel therapies for the management of synovial sarcoma, include the ensuing: 
• Initial PDL1 and CTLA4 studies have shown no benefit [45] 
• Receptor tyrosine kinase inhibitor pazopanib has a promising trend toward better overall survival
• Tazemetostat, an EZH2 inhibitor, has also been studied in INI1 deficient tumours, including synovial sarcoma [46] 
• Early studies on T cell receptor-based immunotherapy directed towards NY-ESO-1 in HLA-A*0201+ patients have demonstrated radiological and clinical benefit [47] 

Gross description

Summations made on the macroscopy pathology examination features synovial sarcoma include the ensuing: [22]

• Gross examination of synovial sarcoma specimen does demonstrate that the tumour is a well circumscribed and frequently multinodular tumour mass. 
• Most synovial sarcoma tumours measure between 3 cm and 10 cm in greatest dimension at the time of initial diagnosis
• Minute synovial sarcoma lesions that measure less than one centimetre (< 1>
• It has been stated that upon gross examination of specimens of synovial sarcoma, the cut surface of the tumour may be noted to be tan or grey, yellow or pink and soft or firm [49] 
• It has also been iterated that upon gross examination of specimens of synovial sarcoma there would tend to be evidence of myxoid change, necrosis, calcifications and metaplastic ossification may be present

Microscopic (histologic) description

The ensuing summations had been made regarding the microscopy pathology examination features of synovial sarcoma of the kidney: [22]

• General statement: [50] 
• 2 main subtypes of microscopy examination features tend to be seen including: biphasic and monophasic spindle cell
• Rarer subtypes also exist: poorly differentiated (round cell), monophasic epithelial, calcifying / ossifying and myxoid
• Biphasic:
• Architecture:
• 2 components: spindle cells and gland-like epithelial structures
• Glandular lumina contain mucin
• Cytologic features:
• Epithelial component has moderate, distinct amphophilic cytoplasm with round to ovoid nuclei
• Rarely, squamous metaplasia can occur
• Monophasic:
• Architecture:
• Infiltrative borders
• Hypercellular fascicular architecture with little intervening stroma
• Can rarely show hyalinization or myxoid change
• Ill-defined nuclear palisading may be seen
• Cytologic features:
• Monotonous cells with scant amphophilic cytoplasm, ovoid to spindled vesicular nuclei with evenly dispersed chromatin and inconspicuous nucleoli
• Nuclei often close enough to overlap with adjacent nuclei
• Poorly differentiated: highly cellular round cells with hyperchromatic nuclei and frequent mitotic activity and necrosis
• Additional features:
  • Characteristically features focal staghorn (or hemangiopericytic), branching vascular pattern, reminiscent of solitary fibrous tumour
  • Mast cells are common
  • Focal calcification can be seen in 33% of cases

Immunohistochemistry staining studies 

Positive stains

It has been stated that immunohistochemistry staining studies in synovial sarcoma cases demonstrate that the tumour cells exhibit positive staining for the following tumour markers:

• TLE1: 80% to 90%, relatively specific and sensitive marker but studies had found more tumours that exhibit TLE1 positivity [51] [52] 
• Cytokeratins: about 90%, variable positivity, depending upon the keratin polypeptide and the component [53] 
  • Epithelial component is consistently positive for CK7, CK8, CK14, CK18, and variable for CK17 (77%), CK13 (25%), CK6 (24%) and CK16 (23%)
  • Spindle cell component usually focal and variably positive for CK7 (79%), CK19 (60%), CK18 (46%), CK8 (45%), CK14 (28%), CK17 (10%), CK20 (6%)
• EMA: 29 - 90%, variable and focal, generally less than cytokeratins. [54] [55] 
• BCL2: 79 - 100% [56] 
• Beta catenin: 30 - 73% [57] 
• Calponin: at least focally positive in all tested cases [58] 
• CD99 (91%), CD56 (100%), CD57 (90%), calretinin (56 - 71%)
• SS18-SSX fusion specific antibody: 95% sensitive, 100% specific
• SSX C terminus antibody: 100% sensitive, 96% specific [59] 
• NY-ESO-1: 76%, strong and diffuse staining [60]

Negative stains

• CD34, desmin, h-caldesmon, myogenin, MyoD1, FL11, WT1 (nuclear staining)
• SOX1O: 93% negative [61] 
• S100: 40% [62] 
• H3K27me3: 60% show loss

Electron microscopy description

• Glandular formation of epithelioid tumour cells with sparse luminal microvilli

Molecular / cytogenetics description

• t(X;18)(p11.2; q11): SYT-SSX1 fusion in 90%, can detect via RT-PCR
• Also t(X;18)(p11.21;q11): SYT-SSX2 fusion, variants can be detected by optimizing RT-PCR [63] [64] 
• p16INK4A gene deletion in 74% [65] 
• High expression of EZH2 helps to distinguish poorly differentiated synovial sarcoma from monophasic and biphasic subtypes [66] 

Differential diagnosis

• Biphasic:
  • Adenocarcinoma:
• Lack spindle cell areas and are typically TLE1-
  • Biphasic mesothelioma:
• Can show sarcomatoid features and cytokeratin positivity but WT1+ and lacks the SSX translocation
  • Glandular nerve sheath tumours:
• Very rarely, malignant peripheral nerve sheath tumour and schwannoma can show glandular features
  • Branchial anlage mixed tumour (ectopic hamartomatous thymoma):
• Composed of spindle cells and epithelial tissue, should also see mature adipose tissue, myoepithelial [removed]CK5/6+, CK14+, SMA+, CD10+, calponin +) [67] 
• Monophasic: [22]
  • Malignant peripheral nerve sheath tumour (MPNST:
• Hypo and hypercellular areas
• SOX10, molecular studies and clinical history are useful in making the diagnosis; often shows focal keratin positivity and TLE1+ in up to 30%
• Also, it can have loss of H3K27me3 in 34% of cases [68] 
  • Cellular Schwannoma:
• Dilated vessels with hyalinized walls
• S100 and SOX10 are diffusely positive, TLE1+ in most cases, which can cause confusion
  • Solitary fibrous tumour:
• CD34+ with a characteristic pattern-less pattern
• STAT6+
• TLE1 can be positive in up to 40%
  • Leiomyosarcoma:
• Often shows more nuclear pleomorphism with brighter eosinophilic cytoplasm
• May be desmin+, SMA+, calponin+, h-caldesmon+
  • Spindle cell rhabdomyosarcoma:
• Desmin+, myogenin +, MyoD1+
  • Adult fibrosarcoma:
• Diagnosis of exclusion when other spindle cell sarcomas have been ruled out
• Dermatofibrosarcoma protuberans with fibrosarcomatous transformation:
• Usually, CD34+ and has an area with more classic histology
• Epithelioid sarcoma:
• Can be keratin+, TLE1+ (30%) and have spindle cell morphology
• CD34+ (50%) and IN11 lost in majority
• Biphenotypic sinonasal sarcoma:
• Has neural and myogenic IHC markers, including S100 and SMA, calponin, desmin or myogenin
• PAX3 rearrangements by FISH
• Sarcomatoid carcinoma:
• Keratin+
• Look for overlying epithelium involved by carcinoma
• TLE1- and lacks the SSX translocation
• Poorly differentiated:
• Small round blue cell tumors:
• SS18-SSX translocation studies and lineage specific markers, such as myogenin, MyoD1, desmin, FL11 are useful
• Molecular studies for PAX3 / PAX7 rearrangements, EWSR rearrangements, CIC-DUX4 and BCOR rearrangements help rule out alveolar rhabdomyosarcoma, Ewing sarcoma and undifferentiated round cell sarcoma (previously Ewing-like sarcomas)

[B] Miscellaneous Narrations and Discussions from Some Case Sreies and Studies Related to Synovial Sarcoma of Kidney

El Chediak et al. [69] reported a 26-year-old male who had experienced recurrent flank pain and visible haematuria over several months. He had had ultrasound of renal tract which demonstrated a lower pole mass that was concerning for renal cell carcinoma. After confirmation of a right kidney tumour, which measured 6 cm, by a contrast-enhanced CT scan, he underwent right radical nephrectomy with para-caval lymph node dissection, at another institute, with pathology examination of the tumour in the hospital which initially was interpreted as depicting features of as an adult type of Wilm’s tumour. After his referral to the institution of El Chediak et al. [69] the pathology slides of the kidney tumour were re=examined by the pathologist of the new establishment, where the morphology and immunohistochemistry staining profiles were analysed, and results were adjudged to be consistent with the diagnostic features of synovial sarcoma of the right kidney. The tumour was described as monophasic and had shown a cellular spindle cell proliferation with a prominent perivascular growth pattern and partial necrosis. The tumour cells had exhibited positive staining for vimentin, BCL-2, CD56, MCK (partial), and negative staining for CD10, 31, 34, 99, 117, CK7, Desmin, SMA, MyoD1, EMA, WT-1, S100, RCC, PAX8, GATA-3, and Synaptophysin (see figure 1).

Figure 1: Partially necrotic, densely cellular proliferation with a prominent perivascular growth pattern (a, H&E stain, 40×). Tumor cells are essentially spindle in appearance (b, H&E stain, 400×), and express vimentin (not shown), focal keratin (not shown), BCL-2 (c, 400×), and CD56 (d, 100×) Reproduced from: [69] under creative commons attribution license. 

Molecular studies on the paraffin-embedded blocks were undertaken to test for the t(X; 18) SYT/SSX fusion transcript, utilising RT-PCR, at the University of Michigan Health System. RT-PCR amplification was undertaken using fluorescent dye-labelled primers, that are specific for the SYT-SS18 and SYT-SSX genes. The PCR products were then detected and sized by capillary electrophoresis to identify the presence of chimeric transcripts. A concurrent internal control was run to ensure the integrity of the mRNA. FISH analysis was also undertaken utilising a break-apart style probe. The results were unfortunately negative due to the low-quality samples. According to these findings, a diagnosis of primary monophasic SS of the kidney was made. It was elected for serial follow up and no adjuvant treatment, thereafter. Six months subsequently, a follow-up CT scan had identified a 1.5 cm x 1.7 cm left lower lobe lung nodule which was suggestive of metastasis. Consequently, he underwent a smooth left lower lobe wedge resection. Fusion gene product analysis on the resected lung tissue, via FISH, revealed SYT-SSX 2 gene rearrangement had confirmed features of SS and a diagnosis of was confirmed. Three months subsequently, he had CT scan of the chest, abdomen, and pelvis which demonstrated another disease recurrence in the nephrectomy surgical bed, with tumour invasion of the inferior vena cava and the presence of conglomerate suspicious aorto-iliac lymph nodes. A multidisciplinary team meeting discussion was held where it was decided to commence the patient on Doxorubicin 50 g/m2 and Ifosfamide 5 g/m2 chemotherapeutic regimen. Following the third cycle, of combination chemotherapy, he had CT scan and MRI, which demonstrated 30% to 50% interval decrease in size of the tumour masses in the right nephrectomy bed and adjacent retroperitoneum, IVC tumour, and distal aortocaval lymph nodes, which indicated partial treatment response. The patient received a total of 5 cycles, with no adjunct side effects. He had a follow-up MRI scan, several months subsequently, which revealed continued decrease in the size of 3 masses at the previous surgical site, inferior vena cava (IVC) tumour invasion, and aortocaval lymph nodes, indicating continued response to treatment. One of the small masses in the nephrectomy bed had almost completely resolved, upon radiology imaging, with no new progression. It was then decided to have the patient undergo surgical resection of the residual masses at the previous surgical bed with removal of the aorto-caval lymph nodes, thrombectomy with vena cava repair. All surgical margins were negative. The final pathology examination of the conceived tumour demonstrated necrosis, with no viable tumour identified. Thus, a complete pathology response was achieved utilising the Adriamycin/Ifosfamide regimen, a year after the initial nephrectomy. A sample of the kidney lysate was again tested for the (X; 18) SYT/SSX fusion transcript via RT-PCR and FISH, and results were negative, suggestive of complete treatment response.

El Chediak et al. [69] made the ensuing conclusions: 

• Primary SS of the kidney is an aggressive rare disease which could be mistaken for other types of renal cell carcinomas. 
• Diagnosis of primary synovial sarcoma of kidney is based upon morphology and molecular studies demonstrating spindle cells and the SYT-SSX translocation. 
• Nevertheless, establishing a correct diagnosis may prove to be difficult. 
• The prognosis of primary synovial sarcoma of the kidney could be enhanced by use of anthracycline based chemotherapy. 
• Moreover, the combination of surgery and chemotherapy had demonstrated positive results. 
• Particularly, we had suggested the use of Ifosfamide and Doxorubicin as a standard chemotherapy to induce complete remission. 
• In view of the fact that primary synovial sarcoma of the kidney may have rapid course with unfavourable outcomes, clinicians need to be aware of the existence of this rare entity, so that timely and appropriate therapy can be commenced.

Kim et al. [70] reported two cases of primary synovial sarcoma of the kidney. Both patients had a mass within the upper part of the right kidney without any primary extrarenal neoplastic lesions. Grossly, the tumours were found to be soft to rubbery masses they had measured 5.5 cm and 5 cm in diameter, respectively. Histologically, both tumours were found to be poorly differentiated synovial sarcoma. The lesions had exhibited a hypercellular solid or lobular growth of round, oval, or short spindle cells in variably solid sheets, in intersecting fascicles, or in a haphazard fashion. Areas of solid aggregation or fascicles of the tumour cells alternating with hypocellular myxoid tissues, together with areas displaying a prominent hemangiopericytoma-like pattern, were identified. Immunohistochemistry staining studies of the tumour had demonstrated that the tumour cells had exhibited diffusely positive staining for vimentin, and a few tumour cells had exhibited positive staining for cytokeratin, epithelial membrane antigen, and neurofilament. The tumour cells exhibited negative staining for S-100 protein, CD34, smooth muscle actin, and desmin, whereas CD56 and CD99 were positive. In both cases, reverse transcription–polymerase chain reaction utilising ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues identified SYT-SSX2 fusion gene transcripts, which were characteristic molecular findings of synovial sarcoma. One patient died 10 months after the initial diagnosis. Kim et al. [71] concluded that these tumours (synovial sarcomas) are unique cases of primary synovial sarcoma of the kidney which were confirmed by molecular study. Divetia et al. [71] stated that the renal parenchyma is a rare site of origin for primary synovial sarcoma (SS). Divetia et al. [71] described the clinicopathology, immunohistochemical, and molecular analysis of 7 cases of synovial sarcoma of the kidney. There were 5 female and 2 male patients, whose ages had ranged between 15 years and 46 years. They had manifested with solitary renal masses which had ranged in size from 10.0 cm to 17.0 cm in greatest dimension. Radical nephrectomy was undertaken in all cases. Upon macroscopy examination, the tumours were noted to be large, partially necrotic, and they were observed to contain smooth-walled cysts in 4 cases. Histologically, the tumours were typified by monomorphic spindle cells with indistinct cell borders arranged in intersecting nodular foci with hypocellular myxoid areas, together with a prominent hemangiopericytomatous pattern. The cysts were lined by hobnailed cells with eosinophilic cytoplasm. Immunohistochemistry staining studies of the tumour had demonstrated that the tumour cells had exhibited positive staining for BCL-2 in all 6 cases in which it was performed, followed by vimentin with positive staining in 4 out of 5 cases and for MIC2 (CD99; positive staining in 2 out of 5 cases, calponin with positive staining in 2 out of 2 cases, and epithelial membrane antigen with positive staining in 1 out of 4 cases. Stains for cytokeratin and CD34 were consistently negative. Reverse transcription–polymerase chain reaction (RT-PCR) utilising RNA extracted from formalin-fixed paraffin-embedded tissues was carried out in 4 cases and SYT-SSX fusion gene transcript, which is the diagnostic hallmark of SS, was detected. Two patients developed pulmonary metastasis and died 6 and 12 months after diagnosis, respectively. Divetia et al. [71] concluded that:

• This series of cases is distinct in terms of its morphological spectrum and confirmation by molecular technique.

Chen et al. [72] reported a case of primary renal synovial sarcoma (SS) in a 48-year-old man. The patient manifested with haematuria and he was found to have a large tumour within his left kidney upon computed tomography scan. Pathology examination of the tumour specimen demonstrated a highly cellular spindle cell neoplasm with minimal pleomorphism. The major differential diagnoses included leiomyosarcoma, hemangiopericytoma, and synovial sarcoma. The presence of focal areas with a biphasic pattern, uniformly positive on immunohistochemistry staining for bcl-2, focally positive staining for epithelial membrane antigen and cytokeratin, and negative immunohistochemistry staining for CD-34, smooth muscle actin and S-100 established the diagnosis. The diagnosis of synovial sarcoma was subsequently confirmed by molecular testing for t(X;18) translocation. Chen et al. [72] stated the following: 

• Since the existence of primary synovial sarcoma (SS) within the kidney was first suggested in 1999, to the best of their knowledge a total of 19 cases including their reported case in 2001 had been reported.
• Even though primary renal SS is rare, these findings indicate that it should be included in the differential diagnosis of spindle cell tumours of the kidney.

Abbas et al. [73] stated that synovial sarcoma (SS) is a soft tissue, generally deep- seated neoplasms which occurs generally within the proximity of large joints. Abbas et al. [73] reported of a case of a 33-year-old man who was diagnosed with primary SS of the kidney which is an extremely rare tumour that accounts for less than 2% of malignant renal tumours. Abbas et al. [73] made the ensuing iterations: 

• Contemporary management of renal synovial sarcoma includes surgical resection and ifosfamide-based chemotherapy and they remain the mainstay of therapy of synovial sarcoma, which is often applied, combined as part of an aggressive treatment approach. 
• By the time of the report of their case, fewer than 50 patients had been described in the English literature. 
• Physicians should be aware of the possibility of malignancy in cystic renal masses and they should have a suspicion for synovial sarcoma, especially when patients with renal masses are young adults. 

Schoolmeester et al. [74] reported the clinicopathology and immunohistochemistry staining features of 16 cases of genetically confirmed primary synovial sarcoma of the kidney. The cases had afflicted 9 men and 7 women whose ages had ranged from 17 years to 78 years and their mean age was 46 years. The tumours were grossly large, solid, and variably cystic and they had measured between 2.2 cm to 19.0 cm and their mean measurement was 8.6 cm. Microscopically, all the tumours were found to be the monophasic type and diffusely immunoreactive for TLE1 and BCL-2. Focal pankeratin positivity was found in just under half. Ten cases were reported to have carried an SS18-SSX2 fusion transcript, and 5 cases had shown an SS18-SSX1 transcript by reverse transcription polymerase chain reaction. The remaining case had demonstrated SS18 rearrangement by fluorescence in situ hybridization. Clinical follow-up information was available for 12 patients and the follow-ups had between 1 month to 77 months with a mean follow-up of 32.5 months. Fourteen patients underwent radical nephrectomy, and 3 patients had lung metastases at presentation. Six patients died of disease within 1 month to 58 months (mean, 31 months) of their diagnosis. Five patients were alive without evidence of disease 12 to 77 months (mean, 39 months) after surgery. A single patient was alive with metastases to the spine 11 months after surgery. Schoolmeester et al. [74] made the following conclusions:

• Synovial sarcoma of the kidney is an aggressive tumour, which is associated with adverse patient outcome in higher than 50% of cases. 
• Synovial sarcoma must be differentiated from morphologically similar lesions of the kidney.
• Perlmutter et al. [75] stated the following: 
• Primary renal synovial sarcomas (SS) are rare tumours of the kidney. 
• Faria first described primary renal synovial sarcoma in 1999. 
• By 2005, twenty-one cases of primary renal synovial sarcoma had been reported. 
• Primary renal synovial sarcomas can exist in either a monophasic or a biphasic pattern. 
• The monophasic variant of primary renal synovial sarcoma is more common and tends to have a better prognosis than the biphasic variant. 
• They had reported the case of a 61year-old woman with a monophasic variant of primary renal synovial sarcoma.

Chung et al. [76] stated that primary synovial sarcoma arising from the kidney is extremely rare. Chung et al. [76] reported two cases with primary renal synovial sarcoma. Chung et al. [76] also reported that both cases were initially diagnosed as renal cell carcinoma. The first case was a 30-year-old woman who had manifested with right flank soreness. The patient had ultrasound scan which demonstrated a multiloculated cystic tumour that measured 9 cm × 7 cm. She underwent hand-assisted laparoscopic radical nephrectomy; there was no recurrence during 15 months of her follow-up. The second case was a 49-year-old woman who had manifested with a palpable mass in the left upper quadrant of her abdomen of 1 month's duration. She had computed tomography scan which demonstrated a heterogeneously contrast-enhanced tumour that measured 13 cm × 11 cm at the left retroperitoneum with displacement of the pancreas and the left kidney. Hand-assisted retroperitoneoscopic radical nephrectomy was undertaken. She had no evidence of recurrence after 27 months of follow-up. Pathology examination of the tumours of the two patients demonstrated histopathology and immunochemistry staining features of synovial sarcoma with coexisting spindle and epithelial cells. Chung et al. [76] made the ensuing suggestion:

• Physicians should be aware of the possibility of malignancy in cystic renal masses and that synovial sarcoma is one of the possibilities.

Dassi et al. [77] reported a 20-year-old female who had presented with a mild left flank pain of one-week duration, with no associated history of haematuria or any other systemic symptoms. Her clinical examination demonstrated a large non-tender lump which had involved her left lumbar and left hypochondriac region. She had computed tomography scan of her abdomen and pelvis which demonstrated large heterogeneously contrast-enhancing mass of 14.3 cm × 9.4 cm × 8.5 cm over the middle-region and lower pole of her left kidney with areas of necrosis within it. An iso-to-hypodense heterogeneously enhancing thrombus was noted in her left renal vein and adjacent portion of the inferior vena cava [see figures 2 and 3].

Figure 2: CT image showing tumor invading almost whole of kidney and involving IVC. Reproduced from [77] under Creative Commons Attribution License.

Figure 3: CT image (coronal) Reproduced from [77] under the Creative Commons Attribution License.

Figure 4: Macroscopically, tumour seen replacing whole of kidney with tumour thrombus in left renal vein. Reproduced from: [77] under the Creative Commons Attribution License.

Figure 5: Tumour composed of spindle cells arranged in intersecting fascicles alternating with hypocellular areas. Reproduced from: [77] under the Creative Commons Attribution License.

Figure 6: Microscopic image showing spindle cells. Reproduced from: [77] under the Creative Commons Attribution License.

Renal cell carcinoma was the provisional suspected pre-operative diagnosis. Intraoperatively, a tumour mass was visualised which had replaced the whole kidney. Left radical nephrectomy was undertaken and left renal vein ligated flush with the IVC after milking the thrombus into the left renal vein. Gross examination of the specimen demonstrated a tumour that measured 12.8 cm × 11cm × 4.5 cm, and which had replaced the entire renal parenchyma, and which had involved the pelvi-calyceal system and medulla with thin rim of cortex seen all around. Tumour thrombus was visualized within the lumen of left renal vein [4]. Microscopy examination of the tumour had demonstrated that the tumour was composed of spindle cells that were arranged in intersecting fascicles, alternating with hypocellular areas, suggestive of monophasic synovial sarcoma (SS) [see figures 5 and 6]. On immunohistochemistry staining studies, the tumour cells were noted to have exhibited positive expression for: bcl-2, calponin, and EMA. Both Mic-2 and CK were focally positive. Molecular analysis had revealed a translocation between the SYT gene on chromosome 18 and SSX on chromosome X, which was consistent with the diagnosis of synovial sarcoma (SS) of kidney.

Dassi et al. [77] made the following conclusions:

• They had described a case of primary synovial sarcoma (SS) of the kidney with inferior vena cava thrombus in a young female. 
• This rare tumour is likely to be confused with other spindle cell tumours of the kidney. 
• An accurate diagnosis, including cytogenetic and molecular studies is imperative. 
• Primary SS should be included in the differential diagnosis when dealing with the spindle cell tumours of kidney. 

Modi et al. [78] reported a Forty-one-year-old male patient who had presented with pain in his left lumbar region and visible haematuria for 1 month. His past and family history is unremarkable. He had been a chronic tobacco chewer for 10 years and a non-alcoholic. He was referred to the cancer centre based upon the findings in his ultrasound scan of a left renal mass. Upon examination he was found to have a normal height, weight, and body mass index for his age. His vital signs were normal and his performance score by ECOG (eastern cooperative oncology group) was 1. Clinically a non-tender palpable mass was felt over his left lumber fossa of around 5 cm × 5 cm with smooth surface and hard consistency. Pallor was present in his sclera and no lymphadenopathy or icterus was identified. He had a CT scan which demonstrated an enlarged left kidney which had almost been completely replaced with heterogeneously hypodense material. There was a hypodense filling defect noted in his left renal vein which had extended up to inferior vena cava suggestive of tumour thrombosis (see figure 7). The results of his laboratory blood test investigations were normal except haemoglobin of 6.7 gm%, serum creatinine of 2.1 mg/dL, and serum BUN of 25 mg/dL.

Figure 7: CT image shows enlarged left kidney and it is almost completely replaced with heterogeneously hypodense material Reproduced from: [78] under the Creative Commons Attribution License.

Figure 8: Lower power view shows round to spindle cells with hemangiopericytoma pattern with areas of hyalinization in between. Reproduced from: [78] under the Creative Commons Attribution License.

Figure 9: High power view shows entrapped normal renal tubules. Reproduced from: [78] under the Creative Commons Attribution License.

Figure 10: The figure shows CD99 positivity. Reproduced from: [78] under the Creative Commons Attribution License.

Figure 11: The figure shows BCL2 positivity. Reproduced from: [78] under the Creative Commons Attribution License.

Histopathology examination of the biopsy specimen from the left renal mass demonstrated round to spindle cells with hemangiopericytoma pattern and area of hyalinization (see figure 8). High power view showed entrapped normal renal tubules (see figure 9). Immunohistochemistry (IHC) staining of the biopsy specimen showed that the tumour cells had exhibited positive staining for CD99 (see figure 10), BCL2 (see figure 11), and vimentin and negative staining for AE1, epithelial membrane antigen (EMA), and leukocyte common antigen (LCA). According to morphological and IHC findings final diagnosis of primary renal synovial sarcoma was made. The patient was found to be clinically inoperable upfront according to Urooncology surgeon. In view of this, he was subsequently offered palliative chemotherapy in form of ifosfamide and adriamycin. He had a CT scan of abdomen which demonstrated partial response after 3 cycles of chemotherapy according to RECIST criteria. Modi et al. [78] made the ensuing conclusions: 

• Primary renal synovial sarcomas (SSs) are very rare type of STS with aggressive biological behaviour and poor prognosis. 
• Surgery is the mainstay of treatment and adjuvant chemotherapy has some role. If not resectable role of chemotherapy is palliative. Tranesh et al. [79] reported a-56-year-old man who had presented to the emergency room with a recent history of haematuria and abdominal pain. He was a non-smoker with no significant past medical history. His blood workup was nonspecific. He had both abdominal and pelvic CT-scans and MRI scan which showed a 6.6 cm enhancing right renal mass with high suspicion for malignancy.  The patient underwent a partial nephrectomy for which intraoperative consultation for diagnosis was provided. The intraoperative consultation was “High grade malignant neoplasm with spindle cell features”. The surgical margin was free of tumour. Macroscopy examination of the partial nephrectomy specimen demonstrated a 175 gm, 8.5 cm × 7.0 cm × 4.5 cm partial nephrectomy with moderate attached perinephric fat. Serial sectioning was remarkable for a 6.6 cm × 5.0 cm × 4.5 cm tan/white partially necrotic and focally haemorrhagic mass. Multiple cystic areas with clear contents were identified. The remainder of the kidney parenchyma was tan/brown with a well-define corticomedullary junction. Microscopically, the tumour was noted to be mitotically active, with monomorphic plump spindle cells and distinct cell borders growing in short, intersecting fascicles. The cysts were lined by mitotically inactive polygonal eosinophilic cells with “hobnailed” epithelium. Properly controlled immunohistochemical staining was undertaken to detect the nature of the tumour cells. Differential diagnoses of this predominantly spindle cell tumour included: sarcomatoid renal cell carcinoma, malignant melanoma, malignant solitary fibrous tumour, nephroblastoma of the adult type, dedifferentiated liposarcoma, rhabdomyosarcoma, leiomyosarcoma and angiolipoma. The tumour cells upon immunohistochemistry staining studies had exhibited positive staining for vimentin, CD99, Bcl-2 and focally positive for staining for cytokeratin (AE1/AE3), synaptophysin, and EMA. The tumour cells had exhibited negative staining for CEA, desmin, CD34, S-100, CD-10, PAX-8, and HMB45. The cystic epithelium was focally positive for cytokeratin (AE1/AE3) and EMA. At that time the diagnostic gold standard for synovial sarcoma was undertaken to demonstrate the fusion of the SYT (Synonyms: SS18-synovial sarcoma translocation, chromosome 18) gene on chromosome 18 to either SSX1 (synovial sarcoma, X breakpoint 1) or SSX2 (synovial sarcoma, X breakpoint 2) gene on chromosome Xp11. RT-PCR study of SYT-SSX genes 1 and 2 fusions were detected by work of Dr. Sarah Kerr and her group at Mayo Clinic Rochester, USA.

Tranesh et al. [79] made the ensuing conclusions: 

• Primary renal synovial sarcoma is a very rare tumour with a non-specific presentation. 
• Clinicians should consider it among the differential diagnosis of renal masses composed of spindle cells. 
• Since morphological demarcation from other tumours may be complicated, additional diagnostic techniques like immunohistochemistry, cytogenetics, and advanced molecular analyses do need to be applied.
• Guimarães et al. [80] stated the following: 
• Primary renal synovial sarcoma (PRSS) is an extremely rare malignancy. 
• The diagnosis of PRSS is unforeseen due to the absence of clinical and radiological typical image aspects. 
• Guimarães et al. [80] reported a case of a 69-year-old man who had manifested with visible haematuria and left lumbar pain. He had contrast-enhanced computed tomography scan of his abdomen and pelvis which demonstrated a solid mass of 8cm diameter within his left kidney and a renal vein tumour thrombus.  The patient subsequently underwent robotic-assisted left radical nephrectomy and renal vein thrombectomy with contemporaneous left adrenalectomy and paraaortic lymphadenectomy. Immunohistochemistry staining studies and genetic analysis revealed confirmed the diagnosis of PRSS. This entity is characterized by abnormal chromosomal translocation t(X;18)(p11.2; q11.2) and consequently the characteristic SYT-SSX fusion gene. Post-operatively, an intensive follow-up protocol was initiated. Chest-abdominal-pelvic CT scan was undertaken every three months, with no evidence of metastasis until nine months following his surgery, when widespread metastatic disease was identified within his liver, pancreas, peritoneum, and lungs. The case was discussed at multidisciplinary evaluation meeting, and doxorubicin was proposed and accepted by the patient. Nevertheless, after one cycle of doxorubicin 75mg/m2, the patient presented with progressive worsening of his condition and he died. Some of the educative guidance iteration discussions of Guimarães et al. [80] include: 
• Due to the disease’s rarity and severity, diagnosis and management of PRSS rely upon a demanding and multidisciplinary approach.
• It has been recommended that patients who are diagnosed to be afflicted by PRSS should be referred to a tertiary centre with an experienced multidisciplinary team specialized in soft tissue sarcoma. [81] 
• In view of the rarity of PRSS, the treatment choices are also debatable. 
• Even though no standard treatment has been globally approved, radical nephrectomy is considered to be the treatment of choice to achieve local control [82]. 
• Adjuvant chemotherapy was reported to have been given in approximately 1/3 of published cases, with a preference for the administration of ifosfamide-based chemotherapy and doxorubicin or epirubicin [82]. 
• According to previous studies, PRRS is associated with an aggressive course with an increased metastasis potential and poor survival outcome [82] [83] [84]. 
• According to Iacovelli et al., the median disease-free survival of PRSS patients was 33 months with a short life expectancy of six months when there is metastatic disease [84]. 

• PRSS is an extremely rare tumour entity. 
• With regard to clinical and radiology image features, PRSS is not easily distinguishable from other renal tumours. 
• Typical aspects of immunohistochemistry staining studies cytogenetics evaluation demonstrating an abnormal chromosomal translocation t(X;18)(p11.2;q11.2) and SYT-SSX gene fusion proteins are key for the diagnosis of PRSS. 
• Radical nephrectomy is the treatment of choice. 
• It has been iterated that adjuvant chemotherapy should be only considered in selected patients since there are few reporters available in the literature. 
• More studies are required to better understand the role of adjuvant treatments.
• Multidisciplinary evaluation is recommended in order to ensure the optimal health care plan for the patient is provided for each patient afflicted by PRSS. 
• Nevertheless, the prognosis of PRSS remains fairly poor.

None.

Acknowledgements to: 

• BMC Urology for granting permission for reproduction of figures and contents of their Journal article under copy right: Copyright © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
• Indian Journal of Urology for granting permission for reproduction of figures and contents of their journal article under copyright: Copyright © Indian Journal of Urology. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Case Reports in Pathology and Hindawi Publishing Limited for granting permission for reproduction of figures and contents of their Journal article under copy right: Copyright © 2014 Gaurang Modi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.