A silver lining … in the ureter: Keratinizing squamous metaplasia with a metallic twist

Abstract

Silver or metallic-appearing urinary tract mucosa is exceedingly rare and typically attributed to exogenous metal exposure. We report a case of a diffusely silver-appearing ureter in a 65-year-old man with a history of squamous cell carcinoma of the bladder and chronic intermittent self-catheterization. Imaging revealed no metallic or calcified material, and histopathology demonstrated extensive squamous metaplasia with marked hyperkeratosis. We hypothesize that dense keratin accumulation produced a pseudo-metallic appearance without true metal deposition. This case highlights a novel gross ureteral appearance likely related to chronic inflammation-induced keratinizing changes, expanding the differential for “silver” urothelial mucosa.

1. Introduction

Squamous cell carcinoma (SCC) of the bladder is a rare malignancy in developed countries and is associated with chronic inflammation and irritation of the urothelium.^1,2 Established risk factors include recurrent urinary tract infections, bladder outlet obstruction, indwelling or intermittent catheterization, and neurogenic bladder. These conditions promote persistent epithelial injury and squamous differentiation, giving rise to keratinizing squamous metaplasia of the urinary tract, commonly referred to as leukoplakia.^2,3 Although most commonly described in the bladder, squamous metaplasia can also involve the ureters and has been implicated as a premalignant condition, particularly in the setting of longstanding inflammation.4, 5, 6, 7.

Silver or metallic discoloration of urinary tract tissues is rare and has historically been attributed to exogenous sources, including silver nitrate exposure, metallic ureteral stents, calculi with mineral deposition, or contrast-related artifacts. In such cases, discoloration is typically localized and associated with an identifiable foreign material or prior intervention.^8,9.

To date, there are no reported cases describing silver or metallic discoloration of the urinary tract in the absence of known exogenous metal exposure. Here, we report a case of a silver-appearing ureter identified intraoperatively during radical cystectomy in a patient with pure SCC of the bladder. Notably, this arose in a background of longstanding bladder inflammation, and the patient had no known exogenous metallic sources.

2. Case presentation

A 65-year-old man with a history of hypertension, hyperlipidemia, and T1 pure SCC of the bladder presented for definitive surgical management. He had no known exposure to agents associated with silver or metallic discoloration of tissues, including silver nitrate, metallic ureteral stents, or urinary calculi. He had no prior surgical history. Notably, he reported performing intermittent self-catheterization multiple times daily for seven years.

Cystoscopy and transurethral resection of the bladder tumor (TURBT) demonstrated diffuse shimmering, silver-white keratinizing debris along the bladder trigone, surrounding but not involving the right ureteral orifice, and involving approximately one-third to one-half of the bladder surface (Fig. 1). The bladder was also noted to have an enlarged capacity with significant trabeculations. TURBT pathology confirmed pure SCC of the bladder. Preoperative computed tomographic (CT) imaging showed no obvious ureteral or bladder calcifications and no radiopaque or metallic-appearing material (Fig. 2).

Fig. 1.

Cystoscopic images of the diffuse keratinizing debris in the bladder taken preoperatively.

Fig. 2.

Preoperative coronary computed tomographic (CT) imaging of the abdomen and pelvis demonstrating no obvious ureteral or bladder calcifications and no obvious radiopaque or metallic-appearing material.

The patient subsequently underwent a robotic-assisted radical cystectomy with pelvic lymphadenectomy and intracorporeal ileal conduit urinary diversion. During left ureteral transection at the level of the bladder, the distal left ureter was noted to have a charcoal-to silver-gray, metallic-appearing mucosa. Following spatulation of the left ureter approximately 4-5 cm proximal to the ureteral orifice during ileal conduit creation, the remaining ureteral mucosa contained the same diffuse discoloration as observed distally (Fig. 3).

Fig. 3.

Intraoperative images of the silver-gray colored, metallic-appearing mucosa of the left ureter observed 4-5 cm proximally from the distal-most ureteral end.

These intraoperative findings were consistent with the bladder discoloration seen on preoperative cystoscopy, but perhaps a bit more pronounced despite no prior ureteral instrumentation. In contrast, the contralateral right ureter appeared grossly normal (Fig. 4). Histopathologic examination of the left distal ureter revealed extensive squamous metaplasia with marked hyperkeratosis (Fig. 5). On routine H and E sections, there was no foreign material and no foreign body reaction. Bladder pathology confirmed squamous cell carcinoma in situ arising in a background of extensive squamous metaplasia. All surgical margins were negative for tumor.

Fig. 4.

Intraoperative image of the grossly normal appearing right ureter.

Fig. 5.

Histopathologic image of the left distal ureter showing extensive squamous metaplasia, negative for tumor.

3. Discussion

We report a unique case of a unilateral, diffusely silver-appearing left ureter identified intraoperatively during radical cystectomy. This occurred in a patient with pure SCC of the bladder arising in the setting of presumed longstanding inflammatory injury from chronic intermittent self-catheterization. While silver or metallic discoloration of urinary tract tissues has been reported in association with exogenous sources such as silver nitrate exposure, this patient had no known exposure to silver-containing agents, metallic ureteral stents, urinary calculi, or prior urologic instrumentation that would account for true metal deposition. Preoperative imaging similarly demonstrated no evidence of metallic or calcified material, and histopathology revealed no evidence of silver deposition, arguing against argyria or argyrosis as an explanation for the observed findings.

Instead, histopathology of the affected ureter demonstrated extensive keratinizing squamous metaplasia with marked hyperkeratosis, consistent with the background pathology identified within the bladder preoperatively. Keratinizing squamous metaplasia arises in response to persistent urothelial injury and chronic inflammation, and in this setting may extend beyond the bladder into the distal ureter. We hypothesize that dense keratin accumulation, potentially combined with cholesterol or lipid-rich debris, produced a reflective mucosal surface that imparted a pseudo-metallic or silver-gray appearance on gross inspection.

Similar reflective phenomena have been described in other keratinizing epithelial disorders and may explain the visual resemblance to argyria in the absence of exogenous silver.10, 11, 12, 13, 14 The concordance between the cystoscopic bladder findings and the intraoperative ureteral appearance further supports a shared inflammatory and metaplastic process rather than true metal deposition. In this case, the patient's prolonged history of intermittent self-catheterization likely contributed to sustained epithelial injury, promoting widespread squamous transformation within the bladder and extending proximally into the ipsilateral ureter. The unilateral nature of the ureteral involvement remains unexplained but may reflect localized differences in inflammatory burden or early proximal extension of metaplastic change on the affected side.

This case expands the known morphologic spectrum of keratinizing squamous metaplasia and highlights that its gross appearance may extend beyond the bladder and present in unexpected ways within the upper urinary tract. Recognition of this phenomenon is clinically relevant, as keratinizing squamous metaplasia is a known premalignant condition and may coexist with or precede SCC of the bladder.

4. Conclusion

We describe the first-ever reported case of a diffusely silver-appearing ureter in the absence of known exogenous metal exposure, occurring in a patient with bladder SCC and extensive keratinizing squamous metaplasia. We propose that chronic inflammation leading to extensive squamous metaplasia and marked hyperkeratosis can produce a reflective, metallic-appearing mucosa that mimics argyria or argyrosis despite no true metal deposition. This case expands the recognized gross spectrum of keratinizing squamous and emphasizes its potential to mimic metallic discoloration in the urinary tract. Awareness of this presentation may aid intraoperative decision-making and reinforces the close association between chronic inflammation, squamous metaplasia, and bladder squamous cell carcinoma.

CRediT authorship contribution statement

Tae-Hee Kim: Data curation, Writing – original draft, Writing – review & editing. John C. Cheville: Data curation, Investigation, Writing – review & editing. Abhinav Khanna: Conceptualization, Data curation, Investigation, Supervision, Writing – original draft, Writing – review & editing.

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Tae-Hee Kim is supported by the Mayo Clinic Grainger Scholar Award.