Renal cell carcinoma with metachronous metastases to the bladder

Introduction: Renal cell cancers account for approximately 2–3% of all cancers. As the use of imaging methods has increased the incidence of these tumors that are often detected incidentally is increasing. Currently, more than 50% of kidney tumors are detected incidentally [1]. Renal cell cancer can metastasize to almost every organ. The lungs, bones, liver, adrenal glands and the brain are common sites of metastases. Case Series: In our case report, we aimed to discuss metachronous bladder metastases detected during the follow-up of two cases that had undergone radical nephrectomy for renal cell cancer in light of current literature information. Conclusion: Renal cell cancer metastasizes to the bladder very rarely, and only a limited number of cases are reported in literature. (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 6 No. 12, December 2015. ISSN – [0976-3198] Int J Case Rep Images 2015;6(12):734–737. www.ijcasereportsandimages.com Karabulut et al. 734 CASE REPORT OPEN ACCESS Renal cell carcinoma with metachronous metastases to the bladder Ibrahim Karabulut, Ertugrul Gazi Ozbey, Ozer Birge, Fevzi Bedir, Mahmut Koc, Mehmet Adiyeke


INtrODUctION
Renal cell cancer accounts for approximately 2-3% of all cancers and annually increases by 2%. Renal cell cancer commonly develops in the sixth and seventh decades and men, and more than 50% of the cases are diagnosed incidentally [2]. Approximately, one-third of the patients presents with metastases at diagnosis [3]. Despite increasing treatment options, the prognosis of renal cell carcinoma patients is poor and the average twoyear survival is 10-20% [4]. Metastases occur mostly to the lungs (75%), and the liver (40%), bones (40%), soft tissue (34%) and the pleura (31%) [5]. Bladder metastases are rare and according to a large-scale meta-analysis only 65 cases have been reported [6]. Metastases can be synchronous or metachronous [7,8]. In our article, we aimed to discuss the metachronous bladder metastases detected in our two cases that had previously undergone radical nephrectomy with the diagnosis of renal cell carcinoma in light of current literature information.

cAsE 1
A 63-year-old male presented to our polyclinic with painless gross hematuria. The detailed anamnesis of the case revealed that he had a right radical nephrectomy performed for a mass in the kidney seven years ago. After reviewing the pathology records of the patient, it was seen that the sections of the tumor from radical nephrectomy of the patient was reported as renal cell carcinoma (clear cell type). It was learnt that he had received sunitinib treatment for approximately three years as the disease was at an advanced stage and was delivered radiotherapy (RT) for the metastasis to the left femur head. There were no features other than the right anterior subcostal incision secondary to the radical nephrectomy in the physical examination. The only pathological finding in the laboratory tests was the hemoglobin level of 8.1 g/dl. While no relapse was observed in the retroperitoneal area in the whole abdominal tomography, a tumorous mass of 5x4 cm originating from the left lateral wall and protruding into the lumen was present in the bladder ( Figure 1). The patient was given two units of erythrocyte suspensions, and the hemoglobin levels were raised up to 10 mg/dl. Under general anesthesia, cystoscopy and transurethral tumor resection were performed. The transurethral tumor resection material was evaluated as renal cell carcinoma (clear cell type) metastases in the histopathological evaluation and the positron emission tomography scan revealed no other metastatic focuses. The case was admitted to a routine follow-up program, and no relapse was identified in the three-month followup cystoscopy. Six months after the bladder tumor was resected, the case was diagnosed with a brain metastasis in the brain surgery clinic he presented with complaints of headaches, nausea and vomiting and these metastases lead to the death of the patient.

cAsE 2
A 53-year-old male presented to our polyclinic with a one-month history of painless intermittent hematuria. It was learned from the case anamnesis that he had undergone a radical nephrectomy operation for a right renal mass approximately three years ago. Six months ago, no pathologies were detected in the last follow-up at the clinic where, operation was performed. There was no feature other than the incision scar secondary to the radical nephrectomy in the physical examination of the case. The laboratory tests performed were normal. The urinary system ultrasonography of the case revealed a 3x3 cm lesion protruded to the lumen thought to be originating from the dome of the bladder. In the cystoscopy performed under general anesthesia the 3x3 cm, solid, pedunculated tumorous lesion originating from the dome of the bladder was observed, and transurethral tumor resection was performed in the same session. The transurethral resection material sent was reported as ( Figure 2) renal cell carcinoma (clear cell type) metastasis. The positron emission tomography scan of the case showed increased metabolic activity at the operation site and magnetic resonance imaging (MRI) scan was performed to evaluate the presence of relapse or residual masses, and no pathologies were detected. No relapse or residual tumor was detected in the cystoscopy performed three months after.

DIscUssION
Approximately, one-third of cases diagnosed with renal cell carcinoma have metastases at diagnosis, and distant metastases develop later in 30% of all cases. Approximately, 2% of bladder tumors are metastases of a primary tumor originating from a different region [9]. Metastatic tumors develop as a result of direct invasion from adjacent anatomical regions or metastases from distant organs. While colon, prostate, cervical and uterine cancers spread to the bladder by direct invasion, the most common sources of the distant organ metastases to the bladder are malignant melanoma and lymphomas. Metastases of renal cell carcinoma to the bladder are very rare [10]. It is not entirely understood how renal cell carcinomas metastasize to the bladder, but it is believed to spread through the hematologic, lymphatic and urinary systems. Among these, the most discussed is hematologic spread. Hematologic metastases develop in two ways: the first is systemic inoculation that is the most common mechanism of renal cell carcinoma spread, and  the second is retrograde spreading through the gonadal vein [11]. Bolkier has shown many connections that allow retrograde tumor spread within the lymphatic system [12]. Another mechanism that could explain the spread of renal tumors to the bladder is the antegrade spread of tumor cells using the upper urinary tract [13]. In a study that reviewed metastases of renal cell carcinoma to the bladder, 23% had bladder metastases coexisting with the kidney tumor and bladder metastases were detected in 77% of the patients after an average of 33 months after the kidney surgery [6]. In one of our cases, the bladder metastasis was detected 84 months after the radical nephrectomy and 36 months after in our another case. In the same study, it was also reported that 62% of the patients had isolated metastases and 38% also had metastases at other focuses [6]. In one of the cases in our study, a bone metastasis coexisted with the bladder metastasis. Both the symptoms and findings of bladder metastases of renal cell carcinoma mimic primary bladder tumors. Generally, the first presenting complaint of cases is gross hematuria and in imaging studies, they appear as limited circular masses extending to the bladder lumen. In cases with detected renal cell cancer, gross hematuria does not appear until the renal pelvis is involved. In cases with significant hematuria, a synchronous transitional cell carcinoma or renal cell carcinoma in the bladder must also be considered [5]. Similarly, the lesions in our cases had regular contours and solid structures in the cystoscopy examination. The treatment of these metastatic tumors of the bladder may change from transurethral resection of the tumor to adjuvant interleukin treatment in select cases and/or partial cystectomy. However, there is no single effective treatment method for metastatic renal cell carcinoma. Most of the patients die in less than one year after the treatment of the metastases [5,9,14,15]. Although rare, cases with long-term disease-free survival have also been reported. In the case report by Raviv et al., the patient had survived disease-free for six years after the transurethral resection of the bladder metastasis [16]. One of our cases died of a brain metastasis six months after the tumor in the bladder was completely removed. No relapse was detected in the follow-up cystoscopy of our another case after resecting the bladder tumor. Eight months have passed since the treatment of the metastatic bladder tumor of our case, and the patient continues to live disease-free.

cONcLUsION
Metastases of renal cell carcinoma to the bladder are very rare. Especially, in cases operated for renal cell carcinoma or bladder tumor cases with coexisting renal masses detected in tests the possibility of bladder metastases of renal cell carcinoma must be considered in the differential diagnosis.

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