Around 50 cases of ipsilateral synchronous renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the renal pelvis were reported in the available literature showing the rarity of this synchronous presentation [1],[2],[3],[4]. Only two possible etiologies have been described explaining the decreased prevalence of this disease. The first etiology posed in 1990 in a Bulgarian study by Stratev highlighted that 31% of tumors in the renal pelvis remain undetected, while 50% of cases of tumors in the ureter are typically unrecognized [5]. The second etiology recently explained on 2009 by Tsai explained that since both RCC and TCC are associated with inflammatory disease of the kidney, this renders imaging modalities difficult to detect their presence and to be mistaken for pyelonephritis should there no structural findings be found [6].

In the context of the paucity of available literature tackling this presentation, we present the case of a 72-year-old male patient with ipsilateral synchronous RCC and TCC of the upper tract.

A 72-year-old male patient, non-smoker, previously healthy, presented with a chief complaint of painless gross hematuria of one month duration. He reported no flank pain or discomfort and a negative family history for renal pathology. An ultrasound of the bladder and upper tract was performed showing the presence of a right, well-defined, cortical isoechoic mass in the lower pole of the right kidney measuring approximately 3 cm in size; in addition to thickening of the bladder wall.

Renal magnetic resonance imaging (MRI) was performed for better characterization of the mass and showed a 3.8×2.2×3.2 cm exogenous lower pole right renal lesion with multiple thickened septations, and a soft tissue component showing heterogeneous signal on T2 images suggestive of RCC. An additional right renal pelvic mass measuring up to 2 cm in the transverse axis was found, neoplastic in nature, suggestive of TCC (Figure 1, Figure 2, Figure 3).

The patient was therefore scheduled for cystourethroscopy and retrograde pyelography of the right upper tract.

Upon admission, the patient had a negative review of systems and an unremarkable physical examination.

Cystourethroscopy demonstrated a bladder neck tumor that was subsequently resected. Retrograde pyelography of the right collecting system demonstrated the presence of a right pelvic mass. Wash cytology from the upper tract was taken and sent for analysis.

Pathology results showed a papillary transitional cell tumor of the bladder invading the lamina propria stage pT1 grade III. Right upper tract cytology showed the presence of high-grade tumor cells. The patient’s hospital stay was smooth and uncomplicated.

Six weeks following the TURBT, the patient presented back for a re-TURBT and a right laparoscopic nephroureterectomy. The patient’s hospital stay was uncomplicated. He was discharged on day four postoperative day and given appropriate recommendations for follow-up.

The pathology results of the specimens taken showed a low grade papillary noninvasive urothelial carcinoma: stage pTa and grade I at the site of the previous bladder resection. The renal mass was shown to be a clear cell renal carcinoma of the lower pole measuring 3 cm in the greatest dimension, and limited to the kidney: Stage pT1a and WHO/ISUP grade 2. There was no extension of the tumor to the renal sinus fat or to the perinephric fat or the renal vein. There was no evidence of rhabdoid or sarcomatoid features, tumor necrosis, or of neoplastic lymphovascular invasion.

In addition, a high grade papillary noninvasive urothelial carcinoma of the renal pelvis was found, with focal squamous differentiation, extending to the middle and lower calyces, and measuring 5 cm in the greatest dimension, without invasion of the renal parenchyma or of the renal sinus fat: Stage pTa.

A low grade noninvasive papillary urothelial carcinoma of the ureter, in a background of diffuse florid Von Brunn nests (numerous urothelial nests arranged in a lobular non-infiltrating pattern in the lamina propria) was noted. The distal ureteral margin or bladder cuff was negative for urothelial carcinoma in situ and for invasive urothelial carcinoma.

Renal cell carcinoma accounts for approximately 90% of all renal malignancies and for 3% of adult cancers. There are several types of renal carcinomas of different prevalence patterns: clear cell RCC representing 70% of RCCs, papillary being 10–15%, chromophobe 5%, and collecting duct tumors with an even lower prevalence [7]. On the other hand, TCC of the renal pelvis or ureter represents 5–7% of all urinary tract tumors while accounting for less than 1% of genitourinary neoplasms [8]. As for their synchronous and ipsilateral presence, there are no up-to-date statistics on its prevalence. Von Eschenbach et al. reported a prevalence of 0.14% for ipsilateral synchronous RCC and TCC of the renal pelvis out of a total of 700 nephrectomies done [9].

In 2005, 47 cases of synchronous renal and transitional cell carcinomas were reported. It was noted that 24% of patients were found to be smokers, but no specific risk factors were identified. In addition, this Spanish review found that the typical presentations of synchronous RCC and TCC were that of RCC and TCC independently; hematuria was found in 90% of the cases, flank pain was present in 19% of cases, and a palpable flank mass was evident in 14% of cases [4].

Possible syndromic associations include the Birt-Hogg-Dubé syndrome (BHD). Birt-Hogg-Dubé syndrome is a rare malignancy susceptibility syndrome caused by a mutation in the folliculin FLCN gene [10]. This syndrome is characterized by renal cell tumors, pulmonary, and dermatological manifestations [10]. Given the lack of associated symptoms and family history, BHD was excluded from the differential diagnosis. On the other hand, a retrospective study showed that 28% of patients with Lynch syndrome manifested upper tract urothelial carcinoma (UTUC) [11]. Lynch syndrome is an autosomal dominant syndrome due to a mutation in four different mismatch repair genes [11]. This syndrome should be suspected in patients younger than 60 years of age presenting with UTUC and/or meeting the “3-2-1” rule of Lynch syndrome [12]. Since this patient is above 60 years old and lacks any relevant familial history, this diagnosis was not further investigated.

Regarding upper tract urinary cytology and its usage for detecting upper tract neoplasms/atypical cells, a review of the literature between the years of 2011 and 2014 showed a sensitivity of 64–74% [13],[14],[15],[16],[17], a specificity of around 50%, and a positive predictive value of 98% [17]. One of the limitations of these studies was that the grading of urine cytology wasn’t performed systematically; in addition, there is no association to accurately predict the degree of invasiveness or the grade of the upper tract pathology with the cytology [14],[17] preventing a deduction of the correlation between the grading on histopathology and a positive upper tract urinary cytology [17]. However, a positive cytology was found in 74.5% and 73% of high-grade and low-grade tumors, respectively, showing the clinical utility of upper tract urinary cytology in detecting neoplastic cells [17].

In 2019, Traeger et al. designed a retrospective study on patients diagnosed with upper tract TCC and RCC. It concluded that serum hepcidin levels and serum GDF-15 levels were found to be elevated in these patients and were associated with decreased survival rates and higher rates of relapse and metastasis. This showed that hepcidin and GDF-15 can be used as a prognostic indicator for such patients. Even though this study is a small cohort study, it shows statistically significant outcomes that warrant larger cohort studies to confirm it [18].

The adopted surgical protocol for RCC is nephrectomy, radical or partial, depending on the characteristics of the tumor [19]. As for upper tract TCC of the kidney, the recurrence rate in the ipsilateral ureteral stump following endoscopic management is reported to be 30–70%, with high grade recurrences in the ureteral stump being associated with poorer prognosis [20]. Hence, nephroureterectomy with a wide bladder cuff represents the main line of treatment for localized high-risk disease.

Overall, the prognosis of synchronous TCC and RCC of the ipsilateral kidney is inconclusive. Based on the review by Arjona et al. (2005) of synchronous renal tumors, the simultaneous occurrence does not worsen the prognosis [7]. Contrarily, Lu et al. found that 24% had metastasis at initial examination, and 34% had bladder neoplasms present concluding the tendency of simultaneous occurrence to exhibit poorer prognosis [19]. However, Dutta et al. reported that the more aggressive of the two tumors is the determinant of prognosis [5].

The European Association of Urology 2021 Guidelines on upper tract urothelial cancer state that, in high-risk patients, neoadjuvant chemotherapy has been associated with significant downstaging at surgery and ultimately survival benefit compared to radical nephroureterectomy (RNU) alone [21]. Due to the rarity of simultaneous and ipsilateral occurrence, attempted prospective trials have been limited [22].

In 2010, the American Cancer Society reported that the prevalence of genitourinary tumors has increased by approximately 10% [23]. All recent studies refer to the 1977 study on 700 nephrectomies conducted by Von Eschenbach et al., to highlight the prevalence and rarity of this disease. This calls for further research on the prevalence of TCC in the renal pelvis with synchronous RCC specifically as there has not been any recent study tackling this simultaneous occurrence. Lastly, definitive recommendations regarding the treatment of ipsilateral synchronous RCC and TCC of the kidney based on prospective studies are required to further characterize the disease.

Ipsilateral synchronous RCC and TCC of the kidney are rare entities with possible genetic associations and no accurate prevalence. The prognosis of the disease is currently a matter of debate as no conclusive data has been determined. There are no definite treatment guidelines as more prospective studies are needed to determine the benefit of the currently recommended treatment regimens.