Robot-assisted radical nephrectomy for primary renal mesenchymal chondrosarcoma: case report and literature review

Abstract As an extremely rare malignant neoplasm, only 12 mesenchymal chondrosarcoma (MC) arising in kidney have been reported to date. Herein, we reported a case of primary renal MC resected with robot assistance, which has not been reported before. According to the cases reported in English literature, we analyzed the characteristics of this rare malignancy and systematically review its treatment.

Here, we report a case of primary renal MC resected with robotic assistance, which has not been reported before to our knowledge. Along with those reported renal MC cases, the features and management of this rare neoplasm will be discussed.

Case presentation
A 62-year-old man, with no significant medical history, was hospitalized with left loin pain and intermittent gross hematuria. Nothing except for mild costovertebral angle tenderness was found abnormal on routine physical examination. The laboratory tests including hematologic studies and urinalysis are shown in Table 1. Abdominal contrast-enhanced CT scan revealed a 14 cm Â 11 cm Â 8 cm heterogeneous lobulated mass, which involved most of the left renal parenchyma, with the calcification foci and cystic spaces. Multiple patchy dense calcifications occupying the expanded renal pelvis and bar filling defect in left renal vein were also detected in the CT scan ( Figure 1). A 0.7 cm lung nodule was identified at the left upper lobe on the chest X-ray. In a bone scan, nuclide was distributed evenly and meristicly over the body except for the 7th thoracic vertebra, which was considered as a metastatic lesion.
With a clinical diagnosis of left renal cell carcinoma with invasion into renal vein and metastasis to the left lung and 7th thoracic vertebra, the patient underwent robot-assisted left radical nephrectomy with renal vein thrombectomy and lymph node dissection after renal arterial embolization.
During the follow-up, the patient presented severe headache caused by skull metastasis after postoperative 2 weeks. Considering the patient's progressively weak condition after surgery, supportive care and pain management were pursued until the patient died of widespread metastases at postoperative 1 month, and no adjuvant chemotherapy or radiotherapy was adopted.
The presence of calcification, the key to an imaging diagnosis of MC [18], was observed in up to 67% of the chondrosarcoma cases according to CT scans [20]. The difference in the peripheral distribution and central distribution of the calcification on CT scans has been reported in several studies [17,20]. The characteristic ring-and-arc mineralization has definite value in qualitative diagnosis [17]. As to renal MC, a total of 10 (within our owe case) out of 12 cases providing information about CT imaging revealed calcifications on CT scans [1,3,[5][6][7][10][11][12][13], while the remaining two patients revealed a heterogeneous mass without calcification [8,9]. On the MR imaging result of the extraskeletal MC cases, equal or low and high-low mixed signal intensity is often shown in T1W1 and T2WI, respectively [17]. A diffused heterogeneous enhancement or nodular enhancement in both calcified and non-calcified areas on enhanced MR imaging is considered as an important diagnostic sign for extraskeletal MC [17,21]. The case    reported by Xu et al. [2] showed a low signal on both T1WI and T2WI on MR imaging. The coexistence of benign tumors' features and imaging performance similar to other malignant soft tissue tumors in extraskeletal MCs made it hard to differentiate from other tumors [17]. The diagnosis of MC remains dependent on pathological examination, which exhibits a characteristic pattern composed of sheets undifferentiated round, oval, or spindle-shaped cells and islands of well-differentiated hyaline cartilage [22,23]. On immunohistochemistry, the areas of well-differentiated cartilage often express non-specific markers of cartilaginous differentiation, such as S-100 protein and CD57 (Leu 7) [22], and relatively specific markers, such as SOX9, a marker that simultaneously shows nuclear positivity in undifferentiated mesenchymal cells [4]. Meanwhile, CD99 expression is common in undifferentiated cell sheets [4,22]. The positive staining for Sox9 along with negative staining for FLI-1 aids in distinguishing MC from Ewing sarcoma [16]. Immunohistochemical staining was performed in seven cases (the seventh case was our case) of all included renal MC patients [2,5,6,8,9,11], in five cases [2,5,9,11] (the fifth case was our case), the cells within the cartilaginous areas are positive for S-100, while CD99 and Vim expressed by the poor-differentiated tumor cells are positive in four [5,6,8] (the fourth case was our case) and six patients [2,5,6,9,11] (the sixth case was our case), respectively.
The treatment of primary MC has no widely accepted guidelines due to its rarity and the lack of appropriate studies and clinical trials to assess the best management [10]. Increasing studies have recommended surgical resection with wide margins as the gold standard to treat extraskeletal MC, but the roles of radiotherapy and chemotherapy remain controversial [5][6][7][8]. Da Vinci robotic surgery has never been performed to treat renal MC before our case presentation, in which the renal MC was perfectly resected in spite of the large tumor size.
Many studies have found that adjuvant radiotherapy for patients with MC plays a role in local tumor control, but the association with overall, disease-free, or metastasis-free survival is insignificant [19,24], that is, patients have the same risk of metastasis or death although they avoided local recurrence.
A consensus on the doxorubicin-based chemotherapy regimens as the adjuvant therapy of MC has been reached [6,7,19]. However, controversy still exists. Kawaguchi et al. [24] found that adjuvant doxorubicinbased chemotherapy did not significantly relate to disease-free survival in the analysis of 19 cases. Meanwhile, Cesari et al. [25] suggested the addition of chemotherapy after complete surgical remission is beneficial in terms of disease-free survival in MC treatment. Gherman et al. [10] recommended neoadjuvant chemotherapy followed by a wide surgical resection as the best management of MC and attempted to establish a standard of care for similar patients. More renal MC cases with extensive follow-up are needed to confirm better treatment.
Many new treatment strategies have been introduced. Shakked et al. [26] introduced therapies targeting the platelet-derived growth factor receptor a proliferation pathway may be beneficial in treating MC. de Jong et al. [27] reported that the inhibition of Bcl-2 family members sensitizes MC to conventional chemotherapy, which provides new methods for treating MC. Many studies have implied that HEY1-NCOA2 rearrangement is not only a diagnostic marker but also a potential therapeutic promoter for MC [28,29]. However, all these new opinions need further verification.
Prognosis of MC differs with the variation of the site of tumor origin [14,30]. The 10-year survival rates for patients with MC vary from 33% to 67% in the literature [16,24,30]. The patient with the smallest tumor burden remained disease-free after 6 years [11], which indicated the importance of early diagnosis and treatment. Close follow-up is extremely important after surgery.

Disclosure statement
The authors report no conflicts of interest.