Successful multidisciplinary management of non-muscle-invasive upper tract urothelial carcinoma in a patient with HIV and concurrent staghorn calculus: a case report

Abstract

Background

The coexistence of upper tract urothelial carcinoma (UTUC) and human immunodeficiency virus (HIV) infection poses unique diagnostic and therapeutic challenges. Literature on the perioperative management and outcomes of curative surgery for UTUC in people living with HIV (PLWH), particularly when complicated by conditions such as staghorn calculi, is exceptionally scarce.

Case presentation

A 65-year-old male presented with a 1-week history of urinary frequency and urgency. Two months prior, he had undergone ureteroscopic laser lithotripsy for a left staghorn calculus (details unavailable) with ureteral stent placement at another institution. During preoperative evaluation for residual stones, his HIV screening returned positive, prompting referral to our center. A subsequent percutaneous nephrolithotomy revealed and permitted resection of a renal pelvic neoplasm. Pathology indicated non-invasive, low-grade papillary urothelial carcinoma. HIV infection was confirmed. Following optimized preoperative management—including nutritional support, urinary tract infection control, and initiation of antiretroviral therapy—the patient successfully underwent laparoscopic left radical nephroureterectomy with bladder cuff excision, combined with cystoscopy and stent removal. Final pathology confirmed non-invasive, low-grade papillary urothelial carcinoma (pTaN0M0) with negative margins.

Conclusion

This case demonstrates that a meticulously coordinated, multidisciplinary approach—encompassing nutritional optimization, infection control, antiretroviral therapy management, and expert surgical planning—enables the safe and effective execution of curative laparoscopic radical surgery for UTUC in PLWH, even when complicated by concurrent conditions such as complex renal calculi. This report contributes a valuable, albeit limited, evidence base for managing this specific patient population.

Introduction

Upper tract urothelial carcinoma (UTUC), encompassing tumors of the renal pelvis and ureter, represents a relatively uncommon entity, accounting for only 5–10% of all urothelial malignancies [1–3]. Its diagnosis is frequently challenging and delayed, as presenting symptoms such as hematuria and flank pain are common yet non-specific [4–6]. For localized, high-risk, or invasive UTUC, radical nephroureterectomy (RNU) with a bladder cuff excision remains the gold-standard curative treatment [7–10].

The co-occurrence of UTUC and human immunodeficiency virus (HIV) infection remains poorly characterized in the literature. HIV infection is associated with an increased risk for certain virus-associated and non-virus-associated cancers, attributed to mechanisms including chronic immune activation [11–16], immunosuppression [17–21], and potentially heightened exposure to carcinogens [22–26]. While the association between HIV and bladder cancer has been documented [27–32], data concerning UTUC in people living with HIV (PLWH) are exceedingly scarce, limited to isolated case reports or small series [33–35].

The management of UTUC in PLWH is complex and extends beyond standard oncologic principles. It necessitates careful consideration of the patient’s immunological status, susceptibility to infections, potential drug–drug interactions between antiretroviral therapy and chemotherapeutic agents, as well as overall nutritional and functional reserve. These factors profoundly influence surgical risk, postoperative recovery, and long-term outcomes. However, current clinical guidelines are strikingly devoid of an evidence-based framework for the perioperative management of PLWH undergoing curative surgery for UTUC.

To address this critical gap, we present a detailed case report of a newly diagnosed HIV-positive male patient in whom a synchronous, low-grade, non-invasive UTUC was discovered incidentally during surgery for residual staghorn calculi. This report delineates a successful, multidisciplinary perioperative strategy that guided the patient through a laparoscopic radical RNU, highlighting the personalized considerations and adjustments required in this complex clinical scenario.

Case presentation

History, diagnosis, and initial management

A 65-year-old male farmer with a history of smoking (over 30 pack-years, quit) and alcohol consumption (approximately 300 mL/day for over 20 years, quit) presented to our hospital with aggravated urinary frequency and urgency for 1 week. Two months prior, he had undergone left ureteroscopic laser lithotripsy for a left staghorn calculus at another hospital (specific surgical details unavailable), followed by ureteral stent placement. He was referred to our institution after testing positive for HIV during preoperative screening for a planned second-stage percutaneous nephrolithotomy (PCNL).

Upon admission, physical examination revealed left costovertebral angle tenderness. Initial laboratory tests indicated hypoalbuminemia (23.6 g/L), stable renal function (serum creatinine: 71 µmol/L), mild anemia (hemoglobin: 100 g/L), elevated D-dimer (2.25 mg/L), and elevated carcinoembryonic antigen (CEA: 9.19 ng/mL). Urinalysis demonstrated marked pyuria and hematuria. Results from electrocardiography, stool routine, tuberculosis antibody assays, cytomegalovirus DNA, Epstein-Barr virus DNA, and (1–3)-β-d-glucan tests were within normal limits. Non-contrast computed tomography (CT) confirmed the presence of multiple residual left renal calculi and the indwelling ureteral stent (Fig. 1A1–A3). Notably, chest CT suggested interstitial lung changes. The HIV diagnosis was confirmed by high-titer antibody detection and positive confirmatory testing. Following consultation with the infectious diseases team, further evaluation was performed, including HIV-RNA (44,030.0 IU/mL; reference < 1.00E+02), cryptococcal antigen (negative), HIV drug resistance testing (negative), head MRI (declined by the patient), and lymphocyte subset analysis. His CD3+CD4+ T-cell count was 599 cells/µL, indicating preserved immune function. Antiretroviral therapy (ART) was subsequently initiated with a bictegravir/emtricitabine/tenofovir alafenamide single-tablet regimen (orally, once daily).

Fig. 1.

Preoperative non-contrast computed tomography (CT) scans. A1 Coronal view with a red arrow indicating the left renal calculus. A2 Sagittal view with a red arrow indicating the left renal calculus. A3 Axial view with a red arrow indicating the left renal calculus

The initial management strategy targeted the symptomatic residual stones. The patient received a course of intravenous albumin supplementation, nutritional support, antiretroviral therapy (ART), and broad-spectrum antibiotics for urinary tract infection, after which he underwent left PCNL. Intraoperative endoscopic inspection (Fig. 2B1–B3) revealed a well-demarcated, papillary lesion within the left renal pelvis. The lesion was completely resected and submitted for pathological evaluation.

Fig. 2.

Intraoperative endoscopic views during left PCNL. B1 Initial panoramic view showing a papillary mass within the renal pelvis. B2 Focused view clearly depicting the overall morphology and attachment site of the papillary neoplasm. B3 Magnified view detailing the local mucosal and surface morphological characteristics of the lesion

Pathological diagnosis and tumor staging

Histopathological examination of the renal pelvic lesion revealed papillary proliferation of atypical urothelial cells, suggestive of urothelial carcinoma (Fig. 3C1, C2). Immunohistochemistry (IHC) was positive for CK7, CK20, p63, and GATA3, with a Ki-67 proliferation index of approximately 40% (Fig. 3C3, C4), confirming a urothelial origin. Light microscopy demonstrated an absent basement membrane on periodic acid–Schiff (PAS) and reticulin staining (Fig. 3C5, C6). Based on the histomorphology and IHC profile from this biopsy, a preliminary diagnosis of renal pelvic urothelial carcinoma was established. Subsequent CT urography showed no evidence of local invasion, lymphadenopathy, or distant metastasis. The bladder was unremarkable.

Fig. 3.

Histopathological, immunohistochemical, and special staining results of the renal pelvic mass. C1, C2 Hematoxylin and eosin (H&E) staining (×100/×200) showing atypical urothelial cells with papillary proliferation, consistent with the morphology of urothelial carcinoma. C3, C4 Immunohistochemical staining demonstrating tumor cell positivity for CK7, CK20, p63, and GATA3, with a Ki-67 proliferation index of approximately 40%. C5, C6 Periodic acid–Schiff (PAS) and reticulin staining revealing an absent basement membrane in the lesional area

Multidisciplinary decision-making and radical surgery

A multidisciplinary committee comprising specialists from urology, oncology, infectious diseases, anesthesiology, and critical care medicine convened for discussion. Given the non-invasive yet potentially multifocal nature of the upper tract urothelial carcinoma (UTUC), the patient’s preserved immune function (CD3+CD4+ T-cell count > 500 cells/µL), and effective early virological suppression evidenced by a plasma HIV-RNA level of 995.0 IU/mL at surgery after approximately three weeks of preoperative antiretroviral therapy (ART), curative surgery was recommended. The committee emphasized the importance of proceeding under optimal conditions: controlled infection, improved nutritional status (serum albumin increased to 33.7 g/L), stable renal function (serum creatinine: 70 µmol/L), and stable ART.

After detailed consultation, the patient and his family provided informed consent for a laparoscopic left radical nephroureterectomy with bladder cuff excision. A transperitoneal approach was utilized. Key surgical steps were performed as follows: initial cystoscopic removal of the ureteral stent and confirmation of no intravesical tumor; patient repositioning for laparoscopic left colonic mobilization; identification and secure ligation of the renal artery and vein; complete mobilization of the kidney within Gerota’s fascia; full-length ureteral dissection down to the bladder; and circumcision of the ureteral orifice with a bladder cuff excision. The specimen was extracted through an extended midline port incision. The total operative time was 120 min, with an estimated blood loss of 20 mL.

Postoperative course and pathological outcome

The postoperative course was uneventful. The patient received standard postoperative care with enhanced surveillance for infection. Ambulation was initiated on postoperative day 2. The urinary catheter was removed on postoperative day 4 after a cystogram confirmed the absence of urinary extravasation. He was discharged in good condition on postoperative day 12 with normal renal function (serum creatinine: 92 µmol/L), although he declined referral for adjuvant oncological follow-up at discharge.

Final pathological examination of the radical specimen (Fig. 4D1, D2) confirmed the preliminary diagnosis: non-invasive, low-grade papillary urothelial carcinoma of the renal pelvis (pTaN0M0). All surgical margins, including the ureteral and bladder cuff margins, were negative for carcinoma. No lymphovascular invasion was identified. The renal parenchyma exhibited changes consistent with chronic obstruction and calculi. Notably, pathological assessment of the distal ureteral margin revealed focal urothelial dysplasia, underscoring the necessity for subsequent close cystoscopic surveillance.

Fig. 4.

Pathological examination images of the radically resected renal pelvic tumor specimen. D1, D2 Pathological staining of the post-radical nephroureterectomy specimen, showing the morphology of low-grade, non-invasive papillary urothelial carcinoma without evidence of invasive growth

Discussion

This case elucidates several critical principles in managing a complex urologic malignancy within the context of a chronic viral infection. First, the diagnostic process was serendipitous. The patient’s symptoms were attributed to nephrolithiasis and infection, masking the underlying malignancy. This underscores the imperative for meticulous inspection during PCNL, particularly in high-risk patients (e.g., smokers, those with chronic irritation from stones/stents), where any abnormal mucosal appearance warrants biopsy [36]. Second, meticulous perioperative management is paramount. PLWH, even with well-controlled infection, may harbor subclinical immune dysfunction and face higher risks of postoperative complications [37–40]. Our strategy was proactive and multifaceted: (1) Host Factor Optimization: Correction of hypoalbuminemia via intravenous supplementation was crucial for wound healing and edema reduction. (2) Control of Comorbid Infection: Aggressive treatment of the urinary tract infection prior to major oncologic surgery minimized sepsis risk. (3) Coordinated ART: The cornerstone of perioperative management in this context lies in maintaining the continuity of antiretroviral therapy (ART), controlling viral load, and conducting individualized assessments of immune status and potential drug interactions. As demonstrated in this case, through multidisciplinary collaboration to optimize preoperative preparation and postoperative monitoring, patients living with HIV can achieve a surgical safety profile approaching that of non-HIV-infected individuals. Therefore, close partnership with infectious disease specialists is essential, as it ensures the timely initiation of a well-tolerated ART regimen, helps avoid potential interactions with perioperative medications, and supports the process of immune reconstitution [41, 42]. The stable CD3+CD4+ T-cell count (> 500 cells/µL) served as a reassuring factor for proceeding with major surgery [43, 44]. Third, the surgical approach warrants emphasis. Laparoscopic RNU offered distinct advantages for this patient. Compared to open surgery, its benefits—reduced postoperative pain, minimal blood loss, quicker return of bowel function, and faster convalescence—are particularly valuable for patients with compromised nutritional status and comorbid conditions such as the interstitial lung changes noted on CT [45–48]. Importantly, this was achieved without compromising oncologic principles, adhering to meticulous dissection and en bloc resection. Fourth, we confronted a known oncologic challenge. Despite negative margins for invasive carcinoma, the final pathology revealing dysplasia at the ureteral margin highlights the well-documented “field effect” carcinogenesis across the urothelium in UTUC [49]. This necessitates stringent, lifelong bladder surveillance via cystoscopy due to the high risk of concomitant or subsequent bladder tumors, alongside periodic imaging of the contralateral upper tract [50, 51].

Further deliberation on the decision for radical surgery: while European Association of Urology guidelines acknowledge kidney-sparing surgery as an option for a solitary, small, low-grade Ta tumor [1], the decision to proceed with radical nephroureterectomy (RNU) in this case was grounded in a composite risk assessment that extended beyond the biopsy grade and stage. This assessment was based on four pivotal considerations. First, the concurrent large (staghorn) calculus and chronic inflammation presented a sustained source of mucosal irritation and an inflammatory milieu, which are well-established risk factors for both urothelial carcinogenesis and recurrence [52]. In this context, conservative management would likely be compromised by suboptimal endoscopic visibility, the challenge of achieving complete tumor clearance, and a higher probability of tumor recurrence within the diseased renal unit. Furthermore, the potential for multifocal disease was underscored. The tumor was discovered incidentally during PCNL, and the final pathology revealed focal urothelial dysplasia at the distal ureteral margin. These findings highlight the presence of extensive “field effect” abnormalities within the ipsilateral urothelium, significantly elevating the risk of residual or recurrent disease if the kidney had been preserved. Moreover, the patient’s significant comorbidities and the need for definitive intervention were critical factors. His clinical burdens—symptomatic stone disease, active urinary tract infection, hypoalbuminemia, and newly diagnosed HIV—collectively argued against a staged approach involving multiple anesthetics and prolonged recovery periods. A single, definitive procedure aimed to resolve both the primary oncological issue and the source of chronic infection/inflammation, thereby optimizing his overall recovery trajectory. Finally, preserved renal function and a healthy contralateral kidney were confirmed preoperatively, making the sacrifice of the diseased left renal unit acceptable from a nephron-sparing perspective. Crucially, the patient himself expressed a strong preference for curative surgery. Therefore, the choice of RNU was based on a holistic evaluation wherein the tumor existed within a kidney marked by long-standing inflammation and stone disease, coupled with evidence of regional field change. Together, these factors decisively tilted the risk-benefit calculus in favor of radical excision.

Postoperative follow-up plan: In accordance with European Association of Urology guidelines for UTUC [1], a structured surveillance plan was discussed with the patient. This includes: (1) Cystoscopic surveillance, with an initial cystoscopy at 3 months postoperatively, then every 6 months for the first 2 years, followed by annual examinations, given the history of urothelial dysplasia at the ureteral margin and the known risk of bladder recurrence; (2) Contralateral upper tract imaging via annual CT urography or MR urography; and (3) Coordinated oncology and HIV care involving regular follow-up with urologic oncology and infectious diseases teams to monitor oncological outcomes, renal function, and HIV status (viral load, CD4+ count) [53]. Although the patient initially declined immediate referral for adjuvant oncological follow-up upon discharge, the critical importance of this structured monitoring regimen was thoroughly communicated. A telephone follow-up at 14 months postoperatively confirmed that the patient was alive, asymptomatic (denying urinary frequency, urgency, dysuria, or hematuria), and in good general condition with normal appetite and sleep. He reported adherence to ART and ongoing follow-up with a local infectious diseases clinic, though his current viral load was not ascertained at that contact. The absence of tumor-related symptoms represents a positive early outcome for the patient.

Finally, the interplay between HIV and UTUC remains poorly understood: Theoretically, chronic immune activation and inflammation in PLWH could foster a procarcinogenic microenvironment [54, 55]. Furthermore, some studies suggest PLWH may present with cancers at a younger age or with more aggressive features [28, 56–60]. A study [61] evaluating the tumor response and safety of camrelizumab in nine HIV-positive patients with urothelial carcinoma (median age 59.7 years, range 41–75; three of whom underwent nephroureterectomy for tumors located in the renal pelvis [n = 2] or ureter [n = 1]) demonstrated promising antitumor activity in post-radical patients with advanced or metastatic disease, showing an objective response rate of 55% and a progression-free survival of 6.2 months (95% CI 9.83–20.63). In another reported case [33], a 70-year-old male diagnosed with HIV 32 years prior and maintained on a long-term antiretroviral regimen of raltegravir (an integrase strand transfer inhibitor), darunavir, and ritonavir (protease inhibitors) with consistently undetectable viral load, subsequently developed left ureteral high-grade urothelial carcinoma (stage T4N2M1 IV) with metastasis to the lung and bone, precluding curative surgery. He subsequently received treatment with enfortumab vedotin (EV) while on an ART regimen consisting of dolutegravir (a minor CYP3A4 substrate), doravirine (a major CYP3A4 substrate), and valacyclovir (not a CYP3A4 substrate), which he has tolerated without major toxicity to date, thereby gaining access to an additional line of anticancer therapy. Therefore, for patients with UTUC and HIV, various treatment options remain available and their therapeutic benefit can be substantial.

In the present case, an elderly patient with a significant smoking and alcohol history presented with a low-grade, early-stage tumor, which does not definitively support an aggressive phenotype. However, it must be clarified that the primary contribution of this report is not to suggest a direct causative link between HIV and UTUC, but rather to demonstrate the feasibility and safety of performing major urologic oncology surgery in PLWH with complex comorbidities. This case adds a critical data point to the exceptionally sparse clinical literature. Our experience underscores that favorable outcomes are achievable through a structured, multidisciplinary approach. Future large-scale, population-based studies are warranted to elucidate any unique epidemiological patterns or biological associations between HIV and UTUC, which is essential for developing tailored screening and management strategies for this distinct patient population.

Conclusion

This case report demonstrates that a diagnosis of HIV infection does not preclude standard oncologic surgical management for UTUC. A successful outcome is contingent upon a structured, multidisciplinary perioperative strategy that addresses the patient’s holistic condition—including nutritional status, infection control, and antiretroviral management—in addition to expert surgical execution. When performed under optimized conditions, laparoscopic radical nephroureterectomy represents a feasible and advantageous approach in this population. Our experience underscores the necessity of maintaining vigilance for synchronous or metachronous urothelial pathology, mandating rigorous long-term surveillance. Further research is required to delineate the unique characteristics and optimal management pathways for UTUC in people living with HIV.

Author contributions

S.P. and TL. conceptualized the review, analyzed the data, and helped to write themanuscript. TH., YM., G.L., HT., QZ., HC., W.C., F.Q., and X.W., helped to write the manuscript and prepared references. All authors have read and agreed to the published version of the manuscript.

Funding

This study has no funding support.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

Ethical review and approval for the publication of this retrospective case report was obtained from the Institutional Review Board (IRB) of Guiyang Public Health Treatment Center. The requirement for written informed consent was waived by the IRB due to the retrospective nature of the study and the use of anonymized data. However, written informed consent for publication of the case details and any potentially identifiable images was explicitly obtained from the patient’s next of kin (his son), who was fully informed about the purpose of this report. We confirm that all methods were carried out in accordance with relevant guidelines and regulations (e.g., the Declaration of Helsinki).

Competing interests

The authors declare no competing interests.