Introduction

Synovial sarcoma (SS) is a soft tissue sarcoma that account for about 5–10% of all soft tissue sarcomas [1,2,3]. The most predominant theory for its origin is the retro-grade differentiation of an undefined mesenchymal cell [3, 4]. It is typical of young adults, average age of 38 years, with a prevalence in male [1], and usually affects the extremities close to articulations (85–95%) or bursa particularly the knee in the popliteal fossas, sinews and the head and neck region (10%) [2, 4], but it has been also identified in other very rare locations such as heart, lungs, prostate, fallopian tubes, foot—which is the most frequent sarcoma of this district—and also kidney [5,6,7,8,9].

Renal sarcomas are less than 1% of all renal neoplasm, which the most common are in order leiomyosarcoma, rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma, angiosarcoma, hemangiopericitoma, undifferentiated pleomorphic sarcoma, rhabdomyosarcoma and synovial sarcoma [10, 11]. Primary renal synovial sarcoma (PRSS) was first described in 1999 by Argani et al. [10] and it represents about the 3% of all renal sarcomas [11]. Due to its rarity—fewer that 200 cases totally knows [1]—and for the diagnostic challenge that it often presents [12,13,14,15]—there are no unanimously accepted standard protocols for diagnosis and treatment [16,17,18,19]. In this article, we described a PRSS case—particularly aggressive and rapidly progressive—that has a negative immunohistochemistry; a literature review of this rare entity is also presented.

Case description

Male, 22 years old, without any history of smoking or alcohol/drugs abuse, referred to our hospital for pain in the left flank and intermittent macrohematuria. By the patient, the symptoms were considered to be completely similar to a previous episode of renal colic due to kidney stones that occurred about 4 years before and were treated with anti-inflammatory drugs and with a little relief. After 1 week, the patient presented at our hospital due to increased symptoms and vomit and asthenia in addiction. After an ultrasound examination that showed an appearance of the kidney subverted by the presence of a coarse solid mass, an abdominal CT scan was performed. The CT scan showed a left mesorenal mass of 6 × 8 × 9 cm, with dishomogeneous enhancement, infiltrating the pancreatic tail, the ipsilateral adrenal gland and the splenic vein as well as the vascular structures of the renal hilum; the residual parenchyma of the left kidney presents delayed impregnation in almost all phases and failure excretion (also caliceal) of iodinated urine even in the urographic phase performed at 10 min (Fig. 1). Subsequently a renal biopsy was performed, with no ultrasound evidence of bleeding. After 3 days of hospitalization, the patient was discharged, again after another utrasound control negative for active bleeding, while awaiting nephrectomy surgery. The outcome of the biopsy was suspicious for monophasic synovial spindle cell sarcoma, although negative for CK AE1/AE3 and PCK26, CK MNF116, EMA-E29, S100-4C4,9, WT1-6F-H2, STAT6-EP325, SMA-1A4, DE-R-11, so the immunohistochemistry maked no contribution in our case. The cytogenetic profile was positive for rearrangements of the SYT gene, thus definitively confirming the diagnostic suspicion. About 10 days after the biopsy, the patient presented again at the hospital for asthenia, dizziness and persistent pain in the left flank. A new abdominal CT scan (Fig. 2) was performed, showing dimensional increase of the lesion up to 12 × 11 × 13 cm and an hyperdense component suggestive for intralesional hematoma, without evidence of active bleeding; effusion up to 6 cm thick apparead in the pouch of Douglas. In the delayed-phase (18 min), the kidney showed a small iodinated urine excretion. The patient was operated. The surgical specimen (omentectomy, left nephrectomy, left adrenalectomy, para-aortic lymphadenectomy) had a total weight of 554 g, with a lardaceous appearance and large hemorrhagic foci. The pathological anatomy investigations conducted on it subsequently confirmed the diagnosis of PRSS, ipsilateral adrenal and perirenal adipose tissue infiltration, without metastatic lymph nodes which, however, were surrounded by infiltrated perilymph node adipose tissue. After chemotherapy with ifofosfamide + epirubicin prescribed by another specialized oncological center, in the follow-up that is currently still underway and now is in its sixth month, the patient has not any local or distant recurrences or postoperative complications.

Fig. 1
figure 1

The first CT scan in three different phases: arterial (a), portal-venous phase (b) and delayed (c)

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Fig. 2
figure 2

The same phases in the CT scan acquired 10 days after biopsy (a–c)

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Discussion

PRSS can replace the whole kidney as a solid mass with cistic and hemorrhagic foci that can may show local infiltrative aspects, especially in the capsule and perirenal adipose tissue [20, 20,21,22,23,24,25,26,27]. Vein thrombosis occurs in 16% of cases especially in inferior infrahepatic vena cava (48.2%), ipsilateral renal vein (34.5%), right cardiac atrium (13.8%) [1]. There are three principal histotypes. The monophasic one, such as in our case, is the most common (75%) and shows ovoid-spindle cells; the biphasic (15% of lesions) has both kind of cells: ovoid shape and epithelial; the last one, poor differentiated is the less common (10%) showing an uniform aggregate of small ovoid-shape blue cells; in only four cases were detected rhabdoid features in monophasic SS [1, 29]. Spindle-shaped cells, an aspect common to all three histotypes, makes pathological differentiation a challenge compared to other renal lesions with similar cells such as Wilms’ tumor, Ewing’s sarcoma, undifferentiated carcinoma and sarcomatoid renal cell carcinoma [14, 15].

Immunohistochemical analyses constitute the most valid aid in orienting towards a diagnosis of SS [1, 14, 15]. Immunopositivity for vimentin, CD99, and BCL2 of the spindle cells and that of cyst epithelium for cytokeratins could be very useful [28, 29] although biphasic variant is often negative to cytokeratins [1]. Moreover cytogenetics and molecular studies (FISH or RT-PCR) can reveal the translocation of t(X;18)(p11.2;q11.2) that is the fusion of SYT gene—chromosome 18—with SSX genes (1, 2 or 4)—chromosome X (SYT-SSX gene fusion protein, SS18-SSX2 is the most frequent), that are found in 90% of SS cases [1, 20, 29,30,31,32,33].

As already noted in the recent review of Guimarães et al. [23], the clinical presentation does not show pathognomonic features suggestive of a diagnosis of renal sarcoma. Ultrasound has a limited role, identifying the sarcoma as a hypoechoic mass with poorly defined margins; however, contrast-enhanced ultrasound (CEUS) shows “slow in and fast out” enhancement which is uncommon in other renal tumors [15]. Especially Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) can help to raise the diagnostic suspicion for PSRR but it does not provide clear and unmistakable signs, as was well summarized recently by Huayanay Espinoza et al. reliable differentiation of the various histologic tumor types is not always possible based solely on the radiologic manifestations. Imaging findings need to be considered in the context of clinical history in corroboration with radiologic–pathologic correlation” [24, 34]. In general it can be said that SS presents itself on radiological imaging with these main characteristics: large demarcated masses, soft-tissue attenuation and heterogeneous enhancement, cystic masses with enhancing intramural nodules and septa. At MRI shows mixed areas of low, intermediate, and high T2 signal intensity; hypointense on T1-weighted images with areas of hemorrhage, fluid levels, and septa; small renal sarcomas can resemble skeletal muscle on T1-wigthed images [24, 29, 35,36,37,38]. The main characteristics which help distinguish a renal sarcoma vs non-sarcoma mass are in truth not so specifics and are substantially the usuals traits of malignant neoplasms: right sided, larger than non-sarcoma renal tumors and has a more irregular tumor shape and margins, showing also local aggressive growth and vessels infiltration [40, 41]. Uhlig et al. have suggested a diagnostic radiological imaging algorithm for the prediction of the histotype of genitourinary tract sarcomas with good results, but the same authors conclude that the only specific imaging regard more fat proportion in liposarcomas versus Ewing’s sarcoma and leiomyosarcoma [40]. CT is able to demonstrate lesions with non-homogeneous contrast impregnation, cystic or septate or with both aspects. A characteristic that could facilitate the recognition of an SS compared to other renal cell carcinoma (including transitional cell carcinoma) or the rare primitive renal lymphoma is the rapid “wash-in” of the arterial phase and a slower “wash-out” in the venous and late phase [25, 26]. Biopsy is not widely used; it has been used in only 8% of cases, prior surgery or chemotherapy [1].

Since it is a rare neoplasm, the therapeutic procedure is still debated. Total nephrectomy, rather than partial one that not shows good outcomes, plays a role in achieving local control, whereas the most frequently used chemotherapy scheme was ifosfamide-based associated with doxorubicin or epirubicin, which offers good results even in the event of relapse [1, 4, 31, 34]. In case of resistance to anthracyclines, trabectedin shows an antitumor effect with 6-months period of disease-free [34, 35]. Nivolumab does not show any effect in SS, compared to what it shows in other sarcomas [36, 37]. What emerges therefore is that it is necessary to find new molecules and new therapeutic options. External radiotherapy associated with chemotherapy is not frequently used (around 3% of cases), and is used above all to decrease local recurrences improving the outcome after surgical treatment [1]. Survival from diagnosis is approximately 33 months (female has greater survival, average 48 months), which is reduced to 6 in the presence of metastatic disease [1, 15, 30]; a 5-year survival rate is also poor, ranging from 59% to 75% [3, 39]. At diagnosis, PRSS is already metastatic in less than 8% of cases [1]. PRSS metastasizes preferentially via blood rather than via lymphatic system and, in order, to lungs, liver, adrenal gland, nodes but also bones and brain [1, 19].

Conclusion

Due to its rarity and the non-specificity of the clinic and overall radiological aspects, the differential diagnosis of PRSS is quite difficult. The real problem is therefore to have elements that allow us to at least suspect the presence of this neoplasm. The diagnostic suspicion of PRSS must be raised when the radiological imaging shows an isolated non-homogeneous renal solid mass, also with cystic aspects and hemorrhagic foci, in the absence of lymphadenopathy. The suspicion must then be further verified and confirmed with histopathological analysis, in particular immunohistochemical—that can be negative as occur in our case—and especially cytogenetic investigations, the real keys to the diagnosis. Currently, no guidelines have yet been published for this rare pathology; however, radical nephrectomy is the treatment of choice. Adjuvant chemotherapy, although successful cases are reported in the literature, is still limited to selected cases. Radiologic–pathologic correlation, multidisciplinary evaluation and shared decision-making processes between professionals and patients surely improve healthcare strategies, and are always recommended in order to have the best possible treatment plans, nevertheless the prognosis is still poor.