INTRODUCTION

Renal cell carcinoma (RCC) is the ninth most common cancer in men, and the fourteenth most common in women[1]. Approximately 90% of kidney cancers are RCCs[2,3]. The most common subtype is renal clear cell carcinoma (RCCC), comprising about 75%-80% of RCCs in surgical series[4]. Almost one-third of patients with RCC present with metastatic disease. The usual metastatic sites are lungs (45.2%), bone (29.5%),lymph nodes (21.8%), liver (20.3%), adrenal gland(8.9%), and brain (8.1%)[5]. Tumors originating primarily in the clivus region are very rare. Chordomas, which are the most frequent tumor affecting that region, represent only 0.15% of all intracranial tumors and 6% of all skull base tumors[6,7]. Common differential diagnoses of clival neoplasms are meningioma, chordoma, lymphoma,pituitary adenoma, nasopharyngeal carcinoma, bone marrow reconversion, and metastatic lesions[8]. Clival metastases from RCCC account for a small proportion of clival tumors. Few cases have been reported.

麦克拉伦谷位于南澳的沿海地区，距离阿德莱德约45分钟车程，自1838年起就开始酿造葡萄酒，是南澳葡萄酒产业的发源地，更是全球最老的葡萄藤种植地点之一。迄今，麦克拉伦谷是澳大利亚最大比例的有机认证和生物动力法认证的葡萄种植区域。该地拥有超过40种的独特地质结构，地质年龄跨度从不到1万年到6亿5千多万年前。而当地的葡萄酒酒庄，绝大部分是小规模精品经营，孕育了多个蜚声国际的品牌如d'Arenberg、Fox Creek、Hardys Wines及Wirra Wirra等。

CASE REPORT

A 54-year-old man presented to the ophthalmology outpatient clinic of our institution with asthenia for one month and acute onset drooping of his right eyelid with diplopia for fourteen days. He had smoked ten cigarettes daily for 30 years. On admission, physical examination revealed palsies of right cranial nervesⅢ, Ⅳ, Ⅵ, and V2 manifesting as right-sided ptosis,diplopia, and decreased sensation over the right cheek.Both pupils were normal in size and reacted to light.

Results of routine laboratory tests were normal apart from a high urinary red blood cell (RBC) of 14.80/hpf. A non-contrast brain magnetic resonance imaging (MRI)showed a mass with irregular margins in the clivus.The mass was invading the sphenoid and cavernous sinuses bilaterally and encasing both carotid arteries.It was isointense on T1-weighted images and slightly hyperintense on T2-weighted images (Figure 1). Brain computed tomography (CT) scan showed obvious osteolysis of the cranial base involving the clivus and both petrous apexes. There was marked enhancement of the clival lesion following intravenous contrast injection(Figure 2).

To obtain a tissue diagnosis and decompress the cavernous sinus, the patient underwent endoscopic endonasal transclival resection of the lesion. Intraoperatively, the tumor was noted to be firm and highly hemorrhagic. Massive bleeding necessitated interruption of the procedure and caused a marked drop in blood pressure. Hemostasis was achieved once the tumor had been partially resected and 400 mL of blood transfused.An early postoperative CT scan showed no evidence of major complications. Immediately after the procedure,the patient’s right-sided ptosis and diplopia improved slightly. Pathological examination of the operative specimen resulted in a diagnosis of clear cell carcinoma(Figure 3A). Ki67 was expressed in 10%-20% of the neoplastic cells and immunohistochemical staining was positive for cytokeratin, vimentin, CK8/18, paired box gene 8 and cluster of differentiation 10. On the sixth postoperative day, the patient underwent a contrastenhanced CT scan of the abdomen, which showed a slightly inhomogeneous, enhancing, roundish mass in the upper pole of the left kidney. No tumor thrombus in the left renal vein or retroperitoneal lymphadenopathy was detected. Contrast-enhanced thoracic CT scan showed no pulmonary metastases (Figure 4). Laparoscopic left radical nephrectomy was performed twelve days after the clival surgery. A 4 cm × 4 cm × 4.5 cm tumor and a 2 cm × 2.5 cm × 2.5 cm isolated tumor satellite focus were noted in the posterosuperior part of the left kidney. The patient did not develop any postoperative complications such as abdominal infection and was discharged ten days after the second surgery.Histopathologic examination of the resected kidney resulted in a diagnosis of RCCC consistent with that of the intracranial tumor (Figure 3). The patient underwent gamma knife for the residual clival lesion one month later. An MRI performed one month after this procedure demonstrated expected postoperative changes. At the four month follow-up, the patient was in good general condition, though his right cavernous sinus syndrome had not improved. Further follow-up is ongoing.

DISCUSSION

Although multiple advances have been made in systemic therapy for RCC, management of metastatic RCC (mRCC) is still challenging[4]. Surgical treatment of our patient, namely partial removal of the metastatic lesion, nephrectomy, and gamma knife treatment were performed successively because he had a solitary metastasis and his physical status was good. The role of radiotherapy in the treatment of RCC remains unclear and it is not recommended[23]. However, several case series have reported that stereotactic radiotherapy is a valuable means of reducing local symptoms from tumor bulk and stabilizing the growth of metastatic lesions in both cranial and extracranial sites[2,24]. Approximately 70% of RCCCs are associated with loss of function of the von Hippel-Lindau gene (VHL). VHL can result in high concentrations of hypoxia inducible factor(HIF) and vascular endothelial growth factor (VEGF),which facilitates tumor-associated angiogenesis[25].Tumor-targeted therapies for RCCC can combat tumor angiogenesis and inhibit tumor cell proliferation. Extended clinical trials of sunitinib and sorafenib have shown that these targeted drugs improve the efficacy of treatment of brain metastasis from RCCC[26,27]. A combination of surgery, stereotactic radiotherapy, and non-targeted and/or targeted agents is often required for management of mRCC. Clinicians should always focus on the goals of treatment and tailor an individual treatment plan to ensure the best possible outcomes.

Table 1 Case reports of clival metastasis from renal clear cell carcinoma

F: Female; M: Male; NA: Not available; AWD: Alive with disease; DOD: Dead of disease.

Position and size of Primary Tumor Ref. Age/sex Symptoms First diagnosis and interval Surgery for clival metastasis Surgery for primary tumor Additional treatment Follow-up Fumino et al[28] 58/M Diplopia Clival metastasis, NA The left kidney,6 cm × 4 cm None Left radical nephrectomy Radiotherapy to the clivus NA Endo et al[29] 59/M Occipital pain,dysarthria, CN XII palsy Clival metastasis, NA The right kidney, 9 cm None None Radiotherapy for the clivus DOD (6 mo)Sepúlveda et al[30] 62/M Sixth nerve palsy,dysarthria,right tongue deviation and right facial paralysis Clival metastasis, NA The right kidney, NA Biopsy None Radiotherapy and palliative care NA Patel et al[31] 59/F Headaches and acute onset cranial nerve neuropathies Clival metastasis, NA The left kidney,NA Endoscopic endonasal near complete resection None Palliative radiation treatment NA Mendelson et al[32] 59/F Headaches and dropping of left eye with double vision Clival metastasis, NA The left kidney,NA Endoscopic decompression of clival lesion None Palliative radiotherapy for renal mass NA Mani et al[12] 55/M Headache and diplopia photophobia of right eye Clival metastasis, NA The left kidney,6.5 cm × 6.0 cm× 5.5 cm None Biopsy External beam radiation therapy and supportive palliative care DOD (6 mo)Gil Salu et al[33] 56/F Diplopia Primary RCCC,8 yr The right kidney, NA Endoscopic endonasal partial resection Right nephrectomy NA NA Santhosh et al[34] 27/F Pain in right lower limb Primary RCCC,NA The right kidney, NA None Right radical nephrectomy Immunotherapy AWD (28 mo)Zhang et al 54/M Asthenia and drooping of his right eyelid with diplopia Clival metastasis, 6 d The left kidney,4 cm × 4 cm ×4.5 cm Endoscopic endonasal biopsy and partial resection Laparoscopic left radical nephrectomy Gamma knife for residual clival lesion AWD (4 mo)

Figure 1 Brain magnetic resonance images. A: Axial T1-weighted magnetic resonance imaging (MRI) showing isointense mass (white arrow) with encasement of the bilateral carotid arteries; B: Sagittal T1-weighted MRI showing sphenoid sinuses involvement (white arrow); C: Axial T2-weighted MRI showing hyperintense central areas suggest cyst degeneration or central necrosis (white arrow).

Figure 2 Brain computed tomography scans. A: Axial computed tomography (CT); B: Sagittal CT showing obvious osteolysis at the cranial base with clivus and bilateral petrous apexes (white arrow); C: Axial CT angiogram showing obvious enhancement (white arrow) after intravenous contrast injection.

Figure 3 Histological findings. A: H and E stain of the clival lesion, 200 ×; B: H and E stain of the left renal mass, 200 × showing clear cells with alveolar growth and separated by reticular separation of thin wall vessels. The two lesions demonstrated similar histopathologic features.

Figure 4 Contrast-enhanced computed tomography scans of abdomen. A: Coronal contrast-enhanced computed tomography (CT) showing slightly inhomogeneous enhancing round-like mass (white arrow) located at the upper pole of the left kidney; B: Axial contrast-enhanced CT showing no tumor thrombus in the left renal vein (white arrow) and retroperitoneal lymphadenopathy revealed.

RCC can be associated with a favorable outcome when diagnosed at an early stage[20]. Unfortunately,30% of these patients have metastatic disease at diagnosis or after treatment of local disease[20]. The largest published retrospective study comprised 286 patients with brain metastases from RCC and their median survival was 9.63 mo[21]. Disease-specific prognostic factors include Karnofsky performance status and the number of brain metastases. A study by Vickers et al[22] revealed that histologic diagnoses of RCCC are more common in patients with brain metastases than in those with metastases to other sites (96%of these patients had clear cell histology). The median survival of patients with brain metastases from RCC is reportedly 14.4 mo, whereas that of patients with RCC without brain metastases is 19.0 mo[22].

哥们儿朝洛蒙拿着饭盒，去楼下打饭（这是哥们儿朝洛蒙要逃跑想出的办法，要不然面对媳妇的质问，他没办法回答）。走到刚才抽烟的地方，看见烟蒂还冒着烟。他停下来，用脚把烟蒂撵灭。随后他又点了根烟，椅着楼门廊的柱子抽起来。虽然刚才他嘴上劝媳妇别瞎想，但他心里也觉得不安。他想着租这房子后的种种迹象：正月回来的奇异的感觉，立交桥下算命先生的谶语，搬家时无缘无故被冰箱砸了的脚趾头，丢了客户被经理没头没脸的斥骂，刚装上好好的骤然爆裂的灯泡，媳妇收拾屋子时在房角砖下发现的符咒，还有这次狗蛋被蝎子的叮咬……难道这之间没有必然联系，只是意外？

Results of routine laboratory tests were normal, apart from a high urinary red blood cell of 14.80/hpf.

The clivus, part of the skull base, is located between the foramen magnum and dorsum sellae and lies deep in the midline in intimate relationship with various critical neurovascular structures[9,11]. In particular, the sixth nerve is very prone to involvement by tumors growing from the clivus and petroclival regions because of its long serpentine course from the brainstem to the superior orbital fissure[12]. Abducens nerve palsy was the presenting manifestation in 46% of patients with chordoma and 47% of those with chondrosarcoma reported by Deconde et al[13]. Above 40% of clival metastases present with isolated sixth nerve palsy according to the review conducted by Dekker et al[10]. That our patient’s tumor extended into the right cavernous sinus may explain the presence of multiple cranial nerve palsies. The possibility of metastatic RCCC should be considered in patients with a clival lesion and cranial neuropathies. Patients with RCC usually present with the classical triad of macroscopic hematuria, abdominal mass, and flank pain. However, many such tumors are asymptomatic and detected incidentally on health checkups or imaging examinations[2].

Most reports of metastases to the clivus have been in the form of case reports, case images, or small series[9]. We performed an extensive review of available reports on clival metastases from RCCC and identified nine patients, including the present case (Table 1).The male/female ratio was 5:4 and mean age was 54 years (range 27-62 years). The clival metastasis was diagnosed first in seven of the nine patients. The main clinical manifestations were sixth nerve palsy, headache,and diplopia. Our results are similar to those reported by Dekker et al[10]. All reported primary RCCCs wereunilateral.

ARTICLE HIGHLIGHTS

Case characteristics

A 54-year-old man with a history of smoking presented with asthenia and acute right cavernous sinus syndrome.

Most reported diagnoses of clival metastases are based on imaging examinations including CT, MRI, positron emission tomography scan with CT (PET-CT) and radionuclide bone scans using technetium or gallium[14].The superior sensitivity of MRI in detecting bone marrow diseases allows precise localization and evaluation of the signal characteristics of clival lesions[8]. Because of its central location, the clivus is best seen on a midsagittal view on MRI. A normal clivus characteristically shows mild enhancement. Low-intensity clival lesions in the marrow tend to be isointense with normal marrow on contrast enhancement. Thus, unenhanced images are more sensitive for detecting clival lesions[8,15]. The usual normal adult clival signal is iso- or hyperintense compared with the pons on T1-weighted images and approximately isointense with the pons on T2-weighted images. Replacement of fatty bone marrow by clival lesions may explain why most clival lesions appear hypointense on T1-weighted images and hyperintense on T2-weighted images[8,12]. Integrated PET-CT has been shown to be an effective means of preoperative staging and follow-up surveillance of patients with skull base tumors (overall sensitivity of 77% and specificity of 81%)[14]. However, clival metastases do not appear to have any distinctive radiological features. Radiologic examinations alone have limited ability to distinguish metastases from primary lesions such as chordomas and chondrosarcomas[16].

Clinical diagnosis

Palsies of right cranial nerves Ⅲ, Ⅳ, Ⅵ, and V2, likely caused by intracranial lesions.

结合新工艺的成本优势，又对比传统上使用湿法工艺处理的含镍1%的低品位红土镍矿进行了侧吹浸没燃烧工艺成本核算，见表5。

Differential diagnosis

Histopathological examination of the operative specimens revealed clear cells in an alveolar pattern, being separated by a reticular meshwork of thin walled vessels.

Laboratory diagnosis

An endoscopic endonasal approach is reported as a promising option for managing clival lesions with minimal morbidity[17]. With the use of a rigid endoscope and angled telescopes, an endoscopic endonasal approach provides a significantly wider and better-illuminated surgical field than traditional open surgeries[18]. In the articles we reviewed, an endoscopic endonasal approach was used in four patients to obtain a biopsy or achieve partial resection. Endoscopic skull base surgeries aided by surgical navigation systems based on preoperative imaging, such as CT and MRI, allow the surgeon to recognize critical structures and maximize the precision of the resection[18]. The application of intraoperative navigated angiosonography techniques for skull base surgery may be helpful in approaching the tumor and avoiding vascular damage[19]. However, endoscopic endonasal approaches have some limitations, including limited working space, reduced maneuverability, and the need for special Instrumentation. It is important to carefully select the most appropriate approach for each patient on the basis of patient- and tumor-related factors as well as the experience of the surgeon.

Imaging diagnosis

Non-contrast brain magnetic resonance imaging demonstrated a mass lesion in the clivus with irregular margins that had invaded the sphenoid and cavernous sinus bilaterally. Brain computed tomography (CT) scan showed obvious osteolysis of the cranial base involving the clivus and both petrous apexes.Contrast-enhanced CT scan of the abdomen showed a slightly inhomogeneous,enhancing, roundish mass in the upper pole of the left kidney.

与原生地文化的断裂和被异质文化的同化造成了赛利亚的文化身份混乱，性别更加深了这种文化困境。书写一方面为赛利亚提供了文化寻根的方式，另一方面为其身份建构指明了一条道路。卡拉米洛披肩是墨西哥传统文化的象征，赛利亚继承了连接家族历史和民族历史的披肩，看到了自身与家族和民族文化的关联，这是她文化身份重构的基础和关键。

Pathological diagnosis

Differential diagnoses included clival chondroma, clival chondrosarcoma,intraosseous lymphoma, and meningioma.

综上所述，市政工程建设虽然会促进城市功能的发展和完善，但是若是管理方面存在缺失，会对都市生态造成严重的破坏。对此，市政管理部门必须将都市生态保护纳入到管理体系中，通过扩大宣传、完善规划协调以及强化管理力度等措施为市政工程建设中都市生态保护创造良好条件，促进城市的可持续发展。

Treatment

Endoscopic endonasal partial resection of the clival metastasis. Laparoscopic left radical nephrectomy of the primary renal clear cell carcinoma (RCCC).Gamma knife for the residual clival lesion.

Related reports

Few reports of clival metastasis from RCCC have been published. These tumors tend to be very aggressive, as evidenced by presentation at an advanced stage of the disease. Multidisciplinary management is necessary.

语文课程标准在“古诗文阅读的评价”中，明确提出了评价小学生古诗词和浅显文言文学习的情况，重点就在于考查学生的记忆和背诵的过程。这就表明在小学阶段，对古诗词的记忆和背诵是非常重要的。

Term explanation

The Karnofsky Performance Scale is a means of classifying patients’ functional impairment. Scores can be used to compare effectiveness of different therapies and assess the prognosis of individual patients. The lower the Karnofsky score,the worse the prognosis.

Experiences and lessons

Clival metastasis from RCCC should be considered in the differential diagnosis of bony lesions of the clivus in patients with cranial neuropathy of sudden onset.Early diagnosis, clinical experience, and multidisciplinary management are crucial for effective treatment of such lesions.

REFERENCES

1 Medina-Rico M, Ramos HL, Lobo M, Romo J, Prada JG.Epidemiology of renal cancer in developing countries: Review of the literature. Can Urol Assoc J 2018; 12: E154-E162 [PMID:29283089 DOI: 10.5489/cuaj.4464]

2 Graves A, Hessamodini H, Wong G, Lim WH. Metastatic renal cell carcinoma: update on epidemiology, genetics, and therapeutic modalities. Immunotargets Ther 2013; 2: 73-90 [PMID: 27471690 DOI: 10.2147/ITT.S31426]

3 Nguyen MM, Gill IS, Ellison LM. The evolving presentation of renal carcinoma in the United States: trends from the Surveillance,Epidemiology, and End Results program. J Urol 2006; 176:2397-2400; discussion 2400 [PMID: 17085111 DOI: 10.1016/j.juro.2006.07.144]

4 Gong J, Maia MC, Dizman N, Govindarajan A, Pal SK. Metastasis in renal cell carcinoma: Biology and implications for therapy.Asian J Urol 2016; 3: 286-292 [PMID: 29264197 DOI: 10.1016/j.ajur.2016.08.006]

5 Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A,Tian Z, Schmitges J, Graefen M, Perrotte P, Menon M, Montorsi F, Karakiewicz PI. Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 2012; 23:973-980 [PMID: 21890909 DOI: 10.1093/annonc/mdr362]

6 Korten AG, ter Berg HJ, Spincemaille GH, van der Laan RT, Van de Wel AM. Intracranial chondrosarcoma: review of the literature and report of 15 cases. J Neurol Neurosurg Psychiatry 1998; 65:88-92 [PMID: 9667567 DOI: 10.1136/jnnp.65.1.88]

7 Samii A, Gerganov VM, Herold C, Hayashi N, Naka T, Mirzayan MJ, Ostertag H, Samii M. Chordomas of the skull base: surgical management and outcome. J Neurosurg 2007; 107: 319-324[PMID: 17695386 DOI: 10.3171/JNS-07/08/0319]

8 Kimura F, Kim KS, Friedman H, Russell EJ, Breit R. MR imaging of the normal and abnormal clivus. AJR Am J Roentgenol 1990;155: 1285-1291 [PMID: 2122682 DOI: 10.2214/ajr.155.6.2122682]

9 Okudo J, Anusim N. Unusual Spread of Renal Cell Carcinoma to the Clivus with Cranial Nerve Deficit. Case Rep Neurol Med 2016;2016: 9184501 [PMID: 27110412 DOI: 10.1155/2016/9184501]

10 Dekker SE, Wasman J, Yoo KK, Alonso F, Tarr RW, Bambakidis NC, Rodriguez K. Clival Metastasis of a Duodenal Adenocarcinoma: A Case Report and Literature Review. World Neurosurg 2017; 100: 62-68 [PMID: 28034818 DOI: 10.1016/j.wneu.2016.12.078]

11 Mohyeldin A, Prevedello DM, Jamshidi AO, Ditzel Filho LF,Carrau RL. Nuances in the treatment of malignant tumors of the clival and petroclival region. Int Arch Otorhinolaryngol 2014; 18:S157-S172 [PMID: 25992140 DOI: 10.1055/s-0034-1395267]

12 Mani A, Yadav P, Paliwal VK, Lal H. Isolated clival metastasis:a rare presentation of renal cell carcinoma. BMJ Case Rep 2017;2017: pii: bcr-2017-221570 [PMID: 28801336 DOI: 10.1136/bcr-2017-221570]

13 Deconde AS, Sanaiha Y, Suh JD, Bhuta S, Bergsneider M, Wang MB. Metastatic disease to the clivus mimicking clival chordomas.J Neurol Surg B Skull Base 2013; 74: 292-299 [PMID: 24436927 DOI: 10.1055/s-0033-1348027]

14 Gil Z, Even-Sapir E, Margalit N, Fliss DM. Integrated PET/CT system for staging and surveillance of skull base tumors. Head Neck 2007; 29: 537-545 [PMID: 17274059 DOI: 10.1002/hed.20545]

15 Chaljub G, Van Fleet R, Guinto FC Jr, Crow WN, Martinez L, Kumar R. MR imaging of clival and paraclival lesions. AJR Am J Roentgenol 1992; 159: 1069-1074 [PMID: 1414777 DOI:10.2214/ajr.159.5.1414777]

16 Movsas TZ, Balcer LJ, Eggenberger ER, Hess JL, Galetta SL. Sixth nerve palsy as a presenting sign of intracranial plasmacytoma and multiple myeloma. J Neuroophthalmol 2000; 20:242-245 [PMID: 11130748 DOI: 10.1097/00041327-200120040-0 0006]

17 Carrabba G, Dehdashti AR, Gentili F. Surgery for clival lesions:open resection versus the expanded endoscopic endonasal approach. Neurosurg Focus 2008; 25: E7 [PMID: 19035704 DOI:10.3171/FOC.2008.25.12.E7]

18 Solares CA, Fakhri S, Batra PS, Lee J, Lanza DC. Transnasal endoscopic resection of lesions of the clivus: a preliminary report.Laryngoscope 2005; 115: 1917-1922 [PMID: 16319599 DOI:10.1097/01.mlg.0000172070.93173.92]

19 Prada F, Del Bene M, Casali C, Saladino A, Legnani FG, Perin A, Moiraghi A, Richetta C, Rampini A, Mattei L, Vetrano IG,Fornaro R, Saini M, Martegani A, DiMeco F. Intraoperative Navigated Angiosonography for Skull Base Tumor Surgery. World Neurosurg 2015; 84: 1699-1707 [PMID: 26193670 DOI: 10.1016/j.wneu.2015.07.025]

20 Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med 1996; 335: 865-875 [PMID: 8778606 DOI: 10.1056/NEJM199609193351207]

21 Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D,Bhatt A, Jensen AW, Brown PD, Shih H, Kirkpatrick J, Schwer A,Gaspar LE, Fiveash JB, Chiang V, Knisely J, Sperduto CM, Mehta M. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys 2010; 77: 655-661 [PMID: 19942357 DOI: 10.1016/j.ijrobp.2009.08.025]

22 Vickers MM, Al-Harbi H, Choueiri TK, Kollmannsberger C,North S, MacKenzie M, Knox JJ, Rini BI, Heng DY. Prognostic factors of survival for patients with metastatic renal cell carcinoma with brain metastases treated with targeted therapy: results from the international metastatic renal cell carcinoma database consortium. Clin Genitourin Cancer 2013; 11: 311-315 [PMID:23684422 DOI: 10.1016/j.clgc.2013.04.012]

23 Kenney PA, Wood CG. Integration of surgery and systemic therapy for renal cell carcinoma. Urol Clin North Am 2012; 39:211-231, vii [PMID: 22487764 DOI: 10.1016/j.ucl.2012.01.005]

24 Lwu S, Goetz P, Monsalves E, Aryaee M, Ebinu J, Laperriere N, Menard C, Chung C, Millar BA, Kulkarni AV, Bernstein M,Zadeh G. Stereotactic radiosurgery for the treatment of melanoma and renal cell carcinoma brain metastases. Oncol Rep 2013; 29:407-412 [PMID: 23151681 DOI: 10.3892/or.2012.2139]

25 Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol 2004; 22: 4991-5004 [PMID: 15611513 DOI:10.1200/JCO.2004.05.061]

26 Guo J, Ma J, Sun Y, Qin S, Ye D, Zhou F, He Z, Sheng X, Bi F, Cao D, Chen Y, Huang Y, Liang H, Liang J, Liu J, Liu W,Pan Y, Shu Y, Song X, Wang W, Wang X, Wu X, Xie X, Yao X,Yu S, Zhang Y, Zhou A; written; CSCO Renal Cell Carcinoma Committee. Chinese guidelines on the management of renal cell carcinoma (2015 edition). Ann Transl Med 2015; 3: 279 [PMID:26697439 DOI: 10.3978/j.issn.2305-5839.2015.11.21]

27 Stukalin I, Alimohamed N, Heng DY. Contemporary Treatment of Metastatic Renal Cell Carcinoma. Oncol Rev 2016; 10: 295[PMID: 27471582 DOI: 10.4081/oncol.2016.295]

28 Fumino M, Matsuura H, Hayashi N, Arima K, Yanagawa M,Kawamura J. [A case of renal cell carcinoma with metastasis in clivus presenting as diplopia]. Hinyokika Kiyo 1998; 44: 319-321[PMID: 9656102]

29 Endo K, Okano R, Kuroda Y, Yamada S, Tabei K. Renal cell carcinoma with skull base metastasis preceded by paraneoplastic signs in a chronic hemodialysis patient. Intern Med 2001; 40:924-930 [PMID: 11579958 DOI: 10.2169/internalmedicine.40.924]

30 Sepúlveda I, Platin E, Klaassen R, Spencer ML, García C, Alarcón R, Ulloa D. Skull base clear cell carcinoma, metastasis of renal primary tumor: a case report and literature review. Case Rep Oncol 2013; 6: 416-423 [PMID: 24019781 DOI: 10.1159/000354575]

31 Patel AA, Kuperan AB, Patel CR, Sharer LR, Liu JK, Eloy JA.Renal cell carcinoma with metastasis to the clivus. NINJ 2013

32 Mendelson ZS, Patel AA, Eloy JA, Liu JK. Endoscopic palliative decompression of the cavernous sinus in a rare case of a metastatic renal cell carcinoma to the clivus. Br J Neurosurg 2015; 29: 430-431 [PMID: 25488389 DOI: 10.3109/02688697.20 14.987217]

33 Gil Salu JL. Metástasis clival tardía de carcinoma renal de células claras. Neurocirugia 2017; 28 (Espec Congr): 296

34 Santhosh KD. Immunotherapy to the rescue in advanced RCC.Available from: URL: http://oncologypro.esmo.org/content/download/125614/2375060/file/2017-ESMO-Preceptorship-I-OParticipant-Clinical-Case-Discussion-Immunotherapy-Advanced-RCC-Santhosh-Kumar-Devadas.pdf