First reported case of peri-ureteric urothelial carcinoma

Abstract

We report the first documented case of peri-ureteric, low-grade urothelial carcinoma presenting over two decades after initial non–muscle-invasive bladder cancer (NMIBC). A 75-year-old male, treated with intravesical BCG, remained recurrence-free for ten years before developing a low-grade bladder recurrence after ten years. Surveillance imaging revealed left hydronephrosis and peri-ureteric thickening despite normal ureteroscopy and negative cytology. CT-guided biopsy confirmed low-grade papillary urothelial carcinoma external to the ureter. Robot-assisted nephroureterectomy showed a non-invasive tumour encasing, but not invading, the ureter, suggesting origin from ectopic urothelial nests. This rare presentation highlights a surveillance blind spot for extraluminal urothelial carcinoma.

1. Introduction

Urothelial carcinoma encompasses malignancies involving bladder, urethra, ureter or pelvicalyceal system. Although bladder cancers account for >90 % of urothelial carcinomas, upper tract surveillance in patients with bladder cancer is of great significance, given existence of concurrent bladder cancer and upper tract urothelial carcinoma, as well as recurrences in the upper tract.¹

We present a truly unique case of peri-ureteric low-grade urothelial carcinoma, arising two decades after initial diagnosis of non–muscle-invasive bladder cancer (NMIBC). This case challenges conventional surveillance paradigms and exposes the diagnostic blind spots in upper tract evaluation, redefining how urologists might approach late and unusual recurrences.

2. Case report

We report a rare and instructive case of a 75-year-old male with a 20+ year journey through the spectrum of urothelial carcinoma, highlighting the unexpected development of upper tract disease after long-term, guideline-adherent bladder cancer surveillance.²

2.1. Initial NMIBC history

Initially diagnosed with non–muscle-invasive bladder cancer (NMIBC) in 1997, the patient underwent complete induction and maintenance intravesical BCG therapy, followed by 10 years of biannual surveillance cystoscopy. Remarkably, no recurrences were observed during this decade-long follow-up as per guideline follow up protocol.

2.2. Surveillance course

At the 10-year mark, however, a low-grade urothelial recurrence was detected, prompting re-initiation of 3-monthly, then 6-monthly, and eventually lifelong annual cystoscopic surveillance. Upper tract monitoring with CT urography remained normal until nearly 10 years post-recurrence.

2.3. New imaging findings

At 10 years post-recurrence, CT of upper tracts demonstrated moderate left pelvicalyceal dilatation with pelvi-ureteric junction obstruction due to appearance of fairly extensive lobular enhancing and thickened upper ureter over craniocaudal extent of 90mm. Additionally, periureteric nodular soft tissue observed which were anticipated to be enlarged lymph nodes versus direct extension in the anteromedial renal fascia measuring up to 7mm (Fig. 1), and the possibility of ureteric involvement was not definitively excluded. On the delayed phase there was stasis of contrast in the dilated pelvicalyceal system without opacification of the left ureter, raising suspicion of obstructive pathology.

Fig. 1.

A - Left periureteric soft tissue across several sections (Coronal) B - Left periureteric soft tissue across several sections (Coronal) C - Left periureteric soft tissue (Axial) D - Left periureteric soft tissue (Coronal) E − Left hydronephrosis, with contrast pooling in left kidney and renal pelvis F – Left ureteric filling defect.

2.4. Endoscopic workup

Retrograde pyelography confirmed a tortuous left upper ureter and a normal right ureter. Rigid left ureteroscopic access was limited by distal tightness. Despite flexible ureteropyeloscopy up to the renal pelvis, no mucosal lesions were visualised. As such, it was considered whether the lesion might have been missed during ureteroscopy or whether it could represent a submucosal or mural process, given the absence of any mucosal abnormality on endoscopic evaluation. Washings were taken which were subsequently negative for high-grade malignancy.

2.5. Percutaneous biopsy and pathology

Crucially, CT-guided biopsy of the periureteric tissue was arranged which revealed low-grade papillary urothelial carcinoma—not within the lumen, but external to the ureter, in the surrounding soft tissue mass. CT chest for staging purpose performed which did not reveal any evidence of metastasis.

2.6. Surgical management and final histology

The patient underwent robot-assisted left nephroureterectomy (Fig. 2). Histopathology revealed a multicystic, non-invasive, low-grade papillary urothelial carcinoma encasing,but not invading or involving, the ureter (Fig. 3). Pathology reports denotes that the tumour is postulated to have arisen from ectopic ureter tissue, corresponding to the periureteric tissue observed on cross sectional imaging. Histologically there were no evidence of invasion and presuming absent lymph nodes, there were no evidence of lymph nodes to metastasize to. This finding also closely mirrored the negative endoscopic appearance and underscores the diagnostic limitations of ureteroscopy in cases of subepithelial or periureteric disease.

Fig. 2.

A - Left kidney and ureter post nephroureterectomy B - Normal ureter lumen (Red arrow) with peri-ureteric tumour C - Serial cross-sections of the entire ureter (distal at top left, proximal at bottom right) following nephroureterectomy, with normal ureteric lumen, and prominent peri-ureteric tumour encasing the ureter externally.

Fig. 3.

Histopathology demonstrating multicystic urothelial carcinoma without ureteric invasion.

2.7. Follow up

The patient continues annual cystoscopic and upper tract CT surveillance, with no evidence of recurrence to date.

3. Discussion

To our knowledge, peri-ureteric low-grade urothelial carcinoma without mucosal involvement has not been previously described, therefore our case represents a previously unreported metastatic pattern in non-muscle invasive bladder cancer (NMIBC).

The radiologic differential diagnosis for a peri-ureteric soft-tissue mass without mucosal involvement is broad and includes Retroperitoneal lymphoma, Inflammatory pseudotumour, retroperitoneal fibrosis, metastasis from other primaries, sarcoma, infective or inflammatory masses. These entities must be considered when endoscopic findings are normal, as they can mimic upper-tract urothelial carcinoma on cross-sectional imaging.

Prognosis in NMIBC is largely determined by the risk of recurrence and progression, which are influenced by a combination of clinical and pathological factors, including histological grading as defined by the latest WHO criteria.³ Despite advances in surveillance and therapy, NMIBC remains notorious for its high recurrence rates, ranging from 31 % to 78 % at five years, and its potential for progression, which can be as low as less than 1 % in low-grade disease but rises to nearly 40 % in very high-risk groups.⁴ The risk of developing upper tract urothelial carcinoma (UTUC) after NMIBC is approximately 1.7 % over ten years, with higher rates observed in more advanced NMIBC stages. This risk increases with time and NMIBC stage categories, with 1.3 % for pTa and 1.9 % for pT1, which subsequently carries a higher mortality and recurrence rates.⁵ This underscores the importance of upper tract imaging in the ongoing management of bladder cancer patients. While intravesical and upper tract recurrences are well characterized, data on extravesical and atypical metastatic patterns remain scarce. The prostatic urethra is the most frequently reported site of extravesical relapse, occurring in up to 39 % of such cases, while fewer than 5 % of NMIBC patients may develop regional lymph node metastases without prior muscle invasion.^6,7 Although it is rare for NMIBC to metastasize directly to distant sites without progression in bladder or regional lymph nodes, this entity has been named as metastatic NMIBC (mNMIBC) by Matthews et al., with the lungs, bones, central nervous system, and gastrointestinal tract being the most commonly affected sites. Isolated case reports have also described metastases to the skin, orbit, testis, and peritoneum.^8,9 The mechanisms underlying these unusual patterns of spread are not fully understood, though lymphatic seeding during TURBT has been proposed as a possible explanation. Outcomes in these patients are generally poor, with reported mortality rates exceeding 50 %.⁹ A previously published case series of four patients reported the presence of small nests of urothelium within the periureteral and peripelvic soft tissues, in patients with established intra-ureteric lesions. Among these, two cases were diagnosed with low-grade non-invasive papillary urothelial carcinoma (UC), one with papillary urothelial neoplasm of uncertain malignant potential (PUNLMP), and one with benign inverted urothelial papilloma. The authors proposed that these ectopic urothelial nests likely resulted from mechanical implantation during prior ureteroscopic instrumentation.¹⁰ In contrast, our patient had no history of upper tract instrumentation, making iatrogenic seeding unlikely. Instead, these nests likely represent ectopic ureteric tissue, possibly remnants of the mesonephric duct or ureteric bud that failed to regress completely during embryological development, rather than metastatic deposits. This is further supported by the histological presence of normal urothelium alongside low-grade, non-invasive urothelial carcinoma, which argues against metastatic disease. Metastatic lesions would typically consist solely of malignant urothelial cells, not benign urothelium, and the absence of invasion or high-grade features makes metastasis highly improbable. The identification of peri-ureteric recurrence in our patient is unprecedented and presents a significant clinical challenge, particularly in the absence of established guidelines for surveillance and management of such cases. The rarity of this metastatic pattern raises important questions about the biological behaviour of NMIBC and highlights the need for heightened clinical vigilance. In the absence of evidence-based recommendations, we opted for a pragmatic approach involving annual cystoscopic and upper tract surveillance. Encouragingly, our patient remains recurrence-free and in good health at the time of this report. We aim to highlight a critical learning point; when imaging raises strong suspicion of malignancy but ureteroscopy is non-diagnostic, alternative diagnostic approaches such as CT-guided biopsy should be pursued. Reliance on ureteroscopy alone may be insufficient, particularly for subepithelial or extra-ureteric disease. This therefore illustrates the limitations of current diagnostic algorithms and supports the need for a more nuanced, suspicion-driven approach. This case not only expands the spectrum of known metastatic sites for urothelial carcinoma but also underscores the necessity for systematic reporting of atypical recurrences, further research into the mechanisms driving such patterns, and the development of tailored surveillance strategies. As our understanding of NMIBC continues to evolve, cases like this one serve as a reminder of the disease's unpredictable nature and the ongoing need for individualized patient care.

4. Conclusion

To the authors’ knowledge, peri-ureteric low-grade urothelial carcinoma without mucosal involvement has not been previously described. This is a novel manifestation of upper tract recurrence that defies traditional endoscopic and mucosal-centric diagnostic approaches. It exposes a critical blind spot in our surveillance tools and calls for a re-evaluation of how we interpret "normal" endoscopic findings in the presence of radiologic abnormalities.

For the urologist, this is a cautionary tale and a call to remain vigilant, and to consider the possibility of extraluminal recurrence in select cases. A normal ureteroscopy does not exclude upper-tract malignancy when disease is extraluminal or subepithelial. When imaging suggests tumour but ureteroscopy is non-diagnostic, tissue biopsy must be pursued. This case not only expands our understanding of the natural history of urothelial carcinoma but may redefine the frontier of upper tract disease surveillance.

CRediT authorship contribution statement

Mandana Gholami: Writing – review & editing, Writing – original draft. Jimmy Lam: Writing – review & editing, Supervision, Conceptualization.

Funding source

No funding source was required for this manuscript.

Decleration of interests

Authors do not declare any conflict of interests.