Later on, a mass over right 1st rib was identified (Figure 1) on the follow-up CT scan 3 months after the radical nephrectomy, and biopsy revealed metastatic clear cell renal cell carcinoma of rib bone. TKI with immunotherapy was suggested by the surgeon but the patient decided on keeping sunitinib monotherapy. The patient tolerated treatment well initially. Follow-up imaging studies showed partial response and a reduction in size bony metastatic lesion.

 

Figure 1 CT with right first rib recurrence (arrow)

 

However, bladder mass was discovered (Figure 2) approximately 6 months following the radical nephrectomy procedure using a CT for therapy response evaluation, and progression was observed later on the 9th and 12th month mark post-operatively. Therefore, transurethral resection of the bladder tumor (TURBT) was performed. Pathological examination revealed positive immunohistochemical staining for vimentin, and showing metastatic ccRCC within the bladder wall without muscle involvement. Given the metastatic nature of the disease, the patient was referred to medical oncology for further management. After discussion with the oncology team, the patient was started on a combination regimen of targeted therapy and immunotherapy with axitinib and pembrolizumab. Regular follow-up with imaging studies was planned to monitor treatment response and disease progression. The patient has no evidence of bladder recurrence after the complete removal of the bladder mass in a 6-month follow-up period.

Figure 2 CT scans showed cancer recurrence at urinary bladder (a) 6 months, (b) 9 month, (c) 12-

 

months after radical nephrectomy, respectively.  

 

Discussion:

In this case, we observe an early recurrence following nephrectomy for metastatic clear cell renal cell carcinoma (ccRCC), presenting as a metastasis to the urinary bladder. It's notable that higher tumor stages are associated with earlier recurrence after nephrectomy, with T3 tumors typically recurring between 17 and 28 months post-operatively.[6] However, in this instance, recurrence manifested in the bladder within less than one year. Rather rarely does RCC metastasize to the urinary tract, whilst Hoffmain reported the first instance of RCC metastases to the bladder in 1907.[7] It seems to be associated with an advanced tumor stage and poor prognosis with a reduced overall survival as described by several reports.[8] Such metastasis can be synchronous or metachronous.[9]

 

The precise pathogenic mechanism driving the spread of renal cell carcinoma (RCC) to the bladder remains unclear. Several possible mechanisms have been proposed in the past, including direct intraluminal transit of tumor cells seeding the distal urothelium, retrograde spread from the renal vein or hilar lymphatics down periureteral veins or lymphatics connecting with pelvic organs, and hematogenous metastasis through the general circulation. [9,10] RCC commonly disseminates via the bloodstream, often leading to the synchronous discovery of widespread metastatic lesions. Conversely, if the primary tumor invades the renal pelvis or at least the collecting duct, urinary spread may be suspected. [11]

 

From a histological standpoint, it's essential to distinguish metastatic ccRCC of the urinary bladder from from clear cell adenocarcinoma of bladder, which tends to affect the female urethra. These adenocarcinomas typically exhibit various growth patterns, including tubular, cystic, papillary, or diffuse. The cells lining the tubules and cysts may display cuboidal, hobnail, or flattened morphology. While metastasis of clear cell carcinomas from other organs to the bladder is rare, it's important to consider other possibilities such as metastatic melanoma, clear cell sarcoma, and seminoma.[12] In this particular case, thorough examination of morphology and immunohistochemistry helped rule out these alternative diagnoses.

 

Conclusions:

Metastasis of renal cell carcinoma (RCC) to the bladder is exceptionally rare and can occur either synchronously or metachronously. It is crucial for clinicians, particularly urologists, to remain vigilant regarding this possibility in patients with a history of RCC postnephrectomy. Despite its rarity, considering this differential diagnosis is essential in evaluating clear cell tumors of the urinary bladder, regardless of whether the patient has a prior history of RCC.