Benign renal tumours and upper tract urothelial carcinoma

• Benign renal tumours are common imaging findings. Angiomyolipoma is a benign fat-containing mesenchymal tumour that can bleed if large, oncocytoma is a benign epithelial tumour that imaging cannot separate from cancer, and simple cysts are harmless.
• Renal cysts are sorted into five Bosniak categories by their imaging features; Bosniak I and II are benign, Bosniak IIF needs surveillance, and Bosniak III and IV usually need surgery or active surveillance.
• Other renal cortical tumours, including oncocytoma and fat-poor angiomyolipoma, cannot be told apart from renal cell carcinoma on CT or MRI, so renal tumour biopsy or excision is sometimes needed.
• A "small renal mass" is usually managed with partial nephrectomy, active surveillance or tumour ablation; the EAU 2026 and AUA 2021 small renal mass frameworks set out these options. ^[7]
• Upper tract urothelial carcinoma is a urothelial cancer of the renal pelvis, calyces or ureter. It is uncommon, it often presents with haematuria, and most patients have invasive disease at diagnosis. ^[8]
• The standard operation for high-risk upper tract urothelial carcinoma is radical nephroureterectomy with bladder cuff removal; a single postoperative bladder instillation of chemotherapy then lowers the risk of bladder recurrence. ^[6]

By the end of this page you should be able to:

1. Describe angiomyolipoma, oncocytoma and renal cysts, and explain why some apparently benign masses still require treatment or follow-up.
2. Recognise tuberous sclerosis in a patient with renal angiomyolipoma and know when mTOR inhibition is used.
3. Use the Bosniak classification to interpret renal cystic masses and plan management.
4. Explain how a small renal mass is evaluated and how active surveillance, ablation and surgery are chosen, using the EAU 2026 and AUA 2021 small renal mass guidance.
5. Recognise the presentation of upper tract urothelial carcinoma and plan imaging and endoscopic diagnosis.
6. Outline radical nephroureterectomy, its oncological principles, bladder cuff management, adjuvant instillation and systemic therapy.
7. Discuss special groups and low-resource practice for both parts of the topic.

The renal cortical tumours that a student must keep separate are summarised below. Approximate proportions come from the EAU 2026 renal cell carcinoma guideline. ^[1]

Benign renal masses are encountered frequently on imaging performed for other reasons. Around 15% of excised renal masses are benign. ^[1] Oncocytoma makes up 4 to 7% of all solid renal tumours and accounts for 30% of benign surgically removed kidney masses. ^[1] Classical angiomyolipoma has an overall prevalence of 0.44%, with 0.6% in women and 0.3% in men; only 5% of patients have multiple angiomyolipomas. ^[1] Renal cysts are even commoner, and the proportion that is complex rises with age.

Tuberous sclerosis complex is an autosomal dominant condition with an estimated prevalence of 1 to 9 per 100,000 people, caused by mutations in TSC1 or TSC2. ^[4] Its characteristic features include cortical dysplasia, subependymal giant cell astrocytoma, dermatological lesions such as angiomyofibromas, lymphangioleiomyomatosis and seizures. ^[4] Renal angiomyolipomas are one of the most recognisable visceral manifestations; small angiomyolipomas are present in most adults with tuberous sclerosis, and they are often bilateral. The lifetime risk of renal cell carcinoma in tuberous sclerosis is under 5%. ^[4] Children with multiple renal cysts or angiomyolipomas, and adults with bilateral angiomyolipomas, should therefore be assessed for tuberous sclerosis and referred for genetic counselling. ^[4]

Simple renal cysts become more common with age and are harmless. Complex cysts that fall into Bosniak IIF, III and IV are uncommon but clinically important because of their malignant potential, discussed below.

UTUC is uncommon. It accounts for only 5 to 10% of diagnosed urothelial cancers. ^[8] The aggregate incidence of upper tract and renal pelvic tumours in the United States is about 7,000 cases per year and is rising with improved detection. ^[8] Most patients have invasive disease at their first presentation, and approximately 9% present with metastatic disease. ^[8] The peak age is the seventh to eighth decades, and men are affected more often than women in most series.

The cause of sporadic angiomyolipoma is not fully understood. It belongs to the perivascular epithelioid cell tumour (PEComa) family, and classic angiomyolipoma is completely benign. Some PEComas can behave aggressively and even metastasise, but this is not the case for classic angiomyolipoma. ^[1] Tuberous sclerosis and, rarely, sporadic lymphangioleiomyomatosis are the main inherited settings. ^[1][4] No modifiable risk factor is established for oncocytoma or simple cysts. Acquired cystic kidney disease in patients with end-stage renal disease carries a much higher risk of renal cell carcinoma and cystic change. ^[3]

Fat-poor angiomyolipoma and oncocytoma are imaging mimics of renal cell carcinoma and cannot be distinguished safely on imaging alone. ^[2] This uncertainty drives much of the management discussion below.

UTUC shares risk factors with bladder urothelial carcinoma. The strongest is tobacco smoking. Other important factors include aristolochic acid exposure (from certain herbal medicines or contaminated grain), analgesic nephropathy, chronic urinary tract infection and irritation, prior bladder urothelial carcinoma (especially high-grade disease), upper tract stones and occupational exposure to aromatic amines. Lynch syndrome, caused by mismatch repair gene mutations, is an important inherited risk factor and should be considered in patients with young onset or a family history of colorectal or urothelial cancer. ^[5][6] Urothelial carcinoma is more common in the renal pelvis than in the ureter, and multifocal disease is not rare.

A classical angiomyolipoma contains mature fat, thick-walled blood vessels and smooth muscle. The vessels are abnormal and lack a normal elastic layer, which explains the main complication, spontaneous retroperitoneal or intrarenal bleeding. Bleeding risk is believed to increase with tumour size and with the angiogenic component of the tumour; the presence of tuberous sclerosis is also a major risk factor. ^[1] Epithelioid angiomyolipoma, a variant consisting of at least 80% epithelioid cells, is rare and potentially malignant, unlike the classical form. ^[1]

Tuberous sclerosis arises from loss of function of the TSC1 or TSC2 tumour suppressors. These proteins normally restrain the mTOR pathway; their loss lets mTOR signalling run unchecked, driving cell growth and angiomyolipoma formation. Blocking mTOR with everolimus can shrink these tumours. ^[1][4]

Oncocytoma is a benign epithelial tumour of oncocytes, cells packed with mitochondria. It has no known metastatic potential and no disease-related deaths have been reported in patients managed with active surveillance. ^[1] Its cells can closely resemble the oncocytic variants of chromophobe renal cell carcinoma, which is why imaging and even core biopsy cannot make a definitive diagnosis. ^[1][2]

A simple cyst has a thin wall and contains homogeneous fluid; it neither enhances nor progresses. Complex cysts develop septa, calcification or solid components. Enhancement of these components is the feature that predicts malignancy. ^[1][2]

UTUC arises from urothelial cells anywhere along the upper collecting system. It may be papillary and exophytic or flat and invasive; the flat lesions are easily missed on imaging. ^[5] It invades locally into the renal parenchyma, the periureteric fat and muscle, then spreads via lymphatics to regional nodes and haematogenously to lung, liver and bone. Tumour cells released during instrumentation can seed the bladder, which is why intravesical recurrence after nephroureterectomy is common and why cystoscopy is part of the initial work-up. ^[5][6]

• Angiomyolipoma grossly is a yellow, soft mass containing fat and abnormal vessels. Microscopically it shows perivascular epithelioid cells, adipocytes and dysmorphic blood vessels. Subtypes include oncocytic angiomyolipoma and angiomyolipoma with epithelial cysts. ^[1]
• Oncocytoma grossly is a mahogany-brown, well-circumscribed mass, often with a central scar. Microscopically it consists of nests and tubules of oncocytes with a benign architecture. ^[1]
• Cystic lesions range from single simple cysts to multiloculated masses. Bosniak IV lesions that are mostly malignant tumours with pseudo-cystic change can look deceptively cystic. ^[1]

UTUC is stratified by grade. Low-grade papillary tumours have a papillary architecture with mild atypia; high-grade tumours show marked atypia and are more often invasive. Histological subtypes, such as squamous or glandular differentiation, occur. Pure urothelial histology is the group most clearly associated with benefit from adjuvant platinum chemotherapy in published studies. ^[5][6]

Most angiomyolipomas, oncocytomas and simple cysts are found incidentally. Large angiomyolipomas may cause flank pain or a palpable mass, and the classic complication is spontaneous retroperitoneal bleeding with flank pain and haematuria, sometimes with shock. ^[1] Epithelioid angiomyolipoma can behave aggressively, but its symptoms are not distinctive.

The single most common symptom is haematuria, usually painless and either visible or microscopic. ^[5] Flank pain from clot or tumour obstruction of the collecting system occurs in 20 to 32% of cases. ^[5] Systemic symptoms such as anorexia, weight loss, malaise, fever, night sweats and cough suggest metastatic disease and carry a worse prognosis. ^[5] A proportion of patients are asymptomatic and are diagnosed when a mass or hydronephrosis is found on imaging done for another reason.

On examination a flank mass may be palpable in advanced disease, and lymphadenopathy or hepatomegaly may be present. Renal function must be recorded, because treatment choices depend on it. ^[6]

The central differential diagnosis is malignant versus benign renal mass. Renal cell carcinoma, angiomyolipoma (especially fat-poor), oncocytoma, metastasis, lymphoma, abscess and pseudo-tumour can all mimic one another on imaging. Urothelial carcinoma of the renal pelvis or ureter enters the differential when the mass is central and haematuria is present, and it is separated by urine cytology and ureteroscopy. ^[2]

In a patient with unexplained haematuria, the alternatives include bladder urothelial carcinoma, renal cell carcinoma, stone disease, urinary tract infection, glomerular disease and benign prostatic disease. Cystoscopy is therefore an integral part of the work-up, to exclude a bladder tumour. ^[5]

CT and MRI characterise a renal mass by looking for enhancement. A renal mass that enhances after contrast contains viable tissue and is therefore not a simple cyst. Oncocytoma and fat-poor angiomyolipoma cannot be reliably distinguished from renal cell carcinoma by CT or MRI, which is why about 15% of surgically removed masses turn out to be benign. ^[2] For complex cysts, CT has poor sensitivity and specificity for Bosniak IIF to III lesions, while MRI and contrast-enhanced ultrasound perform better. ^[2]

Core biopsy of a solid renal mass has a sensitivity of 99.1% and specificity of 99.7% for malignancy in experienced centres, but 8% are non-diagnostic and a definitive diagnosis of oncocytoma cannot be made on needle core. ^[2][3] Biopsy is not indicated when surgery is already planned, nor in frail patients suitable only for watchful waiting. ^[2] Cystic masses are not biopsied unless a solid component is present, which corresponds to Bosniak IV. ^[2]

CT urography has the highest diagnostic accuracy for UTUC, with pooled sensitivity of 92% and pooled specificity of 95%. ^[5] MR urography is reserved for patients who cannot receive CT contrast or radiation. ^[5] Cystoscopy is performed to exclude concomitant bladder cancer. ^[5] Voided cytology may suggest high-grade UTUC; selective barbotage cytology obtained during ureteroscopy detects up to 91% of tumours. ^[5] Diagnostic ureteroscopy allows full inspection, tumour mapping, biopsy and cytology sampling, although it risks undergrading and understaging compared with the final surgical specimen. ^[5] CT of the chest is recommended for high-risk tumours. ^[5]

The Bosniak classification sorts renal cysts into five categories using CT, with MRI and contrast-enhanced ultrasound now included in the updated 2019 version, to predict malignancy risk. The imaging report should state which version was used. ^[1][2]

A meta-analysis of 12 studies with 975 cystic masses assessed by Bosniak 2019 reported malignancy in BII 9%, BIIF 26%, BIII 80% and BIV 88%. ^[2] Less than 1% of stable Bosniak IIF cysts prove malignant during follow-up, but 12% are reclassified to Bosniak III or IV and 85% of those are malignant. ^[1] Surgery in Bosniak III cysts leads to overtreatment in about 49% of cases, because many of these lesions have low malignant potential; active surveillance is therefore an alternative. ^[1]

UTUC is not formally staged on biopsy alone. Ureteroscopic biopsy determines grade well but cannot reliably stage. ^[5] The EAU 2026 UTUC guideline stratifies tumours into low-risk and high-risk groups using a combination of grade, imaging appearance (including whether the tumour looks invasive and whether there is hydronephrosis), tumour focality and the presence of variant histology. ^[5] High-risk disease is the group for whom radical nephroureterectomy is the standard. ^[6]

The EAU 2026 renal cell carcinoma guideline and the AUA 2021 renal mass guideline are the two major frameworks for small renal masses and benign tumours; both support partial nephrectomy for localised tumours, active surveillance for selected patients and tumour ablation when a biopsy has been obtained. ^[3][7]

Angiomyolipoma. Most angiomyolipomas are managed by active surveillance. In one surveillance series only 11% of tumours grew and spontaneous bleeding occurred in 2%, leading to active treatment in 5% of patients. ^[1] The traditional 4 cm cut-off does not by itself trigger treatment. ^[1] Active treatment (selective arterial embolisation, nephron-sparing surgery or thermal ablation) is reserved for persistent pain, ruptured haemorrhage or very large tumours, or for high-risk circumstances such as women of childbearing age and patients with poor access to emergency care. ^[1] In tuberous sclerosis, everolimus, an mTOR inhibitor, can reduce the size of often bilateral angiomyolipomas, as shown in randomised trials; a 25% or greater reduction in tumour volume at four and six months was seen in 55.6% and 71.4% of patients in a small phase II trial, with toxicity causing withdrawal in some. ^[1] Embolisation remains the option for life-threatening bleeding. ^[1]

Oncocytoma. Because imaging cannot diagnose oncocytoma definitively, a renal mass believed to be oncocytoma is usually either excised or biopsied and then observed. Active surveillance is an acceptable alternative to surgery or ablation for biopsy-proven oncocytoma or other oncocytic tumours, according to the EAU 2026 guideline. ^[1][3] Oncocytomas grow slowly, at about 2 mm per year, and no metastases or cancer deaths have been reported on surveillance. ^[1]

Cysts. Bosniak I and II cysts are benign and need no follow-up. Bosniak IIF cysts are observed for up to five years. Bosniak III cysts can be treated as localised renal cell carcinoma or observed, because about half are overtreated by surgery. Bosniak IV cysts are managed as localised renal cell carcinoma. ^[1][2]

Active surveillance suits older or comorbid patients. In a pooled systematic review of 18 cohorts and 2,066 patients, metastatic disease developed in only 2.1% during a mean follow-up of 53 months; for tumours under 4 cm the metastasis rate was 1.8%. ^[3] In the multi-institutional DISSRM study of 497 solid masses under 4 cm, the median growth rate was 0.09 cm per year and no patient on surveillance developed metastatic disease or died of renal cell carcinoma; five-year cancer-specific survival was 99% to 100%. ^[3] A core biopsy helps classify the histology, because clear-cell masses grow faster than papillary type 1 masses. ^{[3] [2]}

Kidney-sparing treatment is preferred for low-risk UTUC because oncological outcomes match those of nephroureterectomy while preserving renal function. ^[6] Options include endoscopic laser ablation with ureteroscopy, percutaneous antegrade access for renal pelvic tumours that are difficult to reach retrogradely, segmental or distal ureterectomy with re-implantation, ureteral resection and, in selected patients, chemoablation with mitomycin-containing reverse thermal gel. ^[6]

Endoscopic ablation needs careful surveillance. Roughly one in two patients develops an ipsilateral upper tract recurrence within two years, so an early second-look ureteroscopy within eight weeks is recommended. ^[6] Systematic review evidence shows survival equivalent to nephroureterectomy but higher local recurrence and more repeat procedures. ^[6]

Segmental ureterectomy for distal ureter tumours has a low ipsilateral upper tract recurrence rate of 0 to 18%, compared with 25 to 85% after endoscopic kidney-sparing treatment. ^[6] Mitomycin gel chemoablation in a single-arm phase III trial of 71 patients with low-grade tumours under 15 mm achieved a complete response in 58%, but ureteric stenosis was common (44%), and only 56% of complete responders remained disease-free at one year. ^[6]

Adjuvant instillations after kidney-sparing treatment are more controversial. Antegrade or retrograde mitomycin or bacillus Calmette-Guerin instillation has been studied for carcinoma in situ, but the evidence base is small and retrospective, and recurrence rates are comparable to untreated patients, questioning benefit. An early single instillation of mitomycin after low-grade kidney-sparing treatment might reduce local recurrence. ^[6] No data currently support adjuvant bladder instillation after kidney-sparing surgery, because trials were confined to patients who had nephroureterectomy. ^[6]

Radical nephroureterectomy (RNU) is the standard treatment for high-risk non-metastatic UTUC. ^[6]

Surgical approach. Open, laparoscopic and robotic approaches have similar oncological outcomes, with minimally invasive approaches giving a shorter hospital stay and fewer perioperative complications at the cost of a higher risk of intravesical recurrence. ^[6] Whatever the approach, the operation is performed on oncological principles: en bloc removal of the kidney, ureter and bladder cuff, and avoiding entry into the urinary tract except for the bladder cuff excision, and only after the ureter has been clipped and the bladder drained. ^[6]

Bladder cuff management. The distal ureter and its orifice must be removed with the specimen; incomplete bladder cuff excision raises the risk of bladder tumour recurrence. Transvesical, extravesical and endoscopic approaches have similar cancer-specific survival, though the impact on intravesical recurrence is less clear, with endoscopic cuff excision possibly carrying a higher recurrence risk. ^[6]

Lymph node dissection. There is no high-level evidence for routine lymphadenectomy in UTUC, but template-based dissection based on tumour location may reduce local recurrence and improve cancer-specific survival, with a low added complication risk. ^[6]

Kidney-sparing options in high-risk disease. For carefully selected high-risk tumours limited to the distal ureter, distal ureterectomy with re-implantation can match long-term oncological outcomes while preserving renal function, but local and intravesical recurrence are more frequent. ^[6] Ureteroscopic laser ablation or segmental ureterectomy may be offered case by case for high-risk patients whose features are closer to the weak high-risk criteria, or for patients with imperative kidney-sparing indications such as a solitary kidney, bilateral disease or severe chronic kidney disease. ^[6]

Perioperative systemic treatment. Neoadjuvant cisplatin combination therapy can produce pathological complete response in 14 to 19% of high-grade or cT2 to T4 disease and downstage more than 60% of patients, without compromising surgery. ^[6] Adjuvant platinum-based chemotherapy is the better-established option: the POUT phase III trial of 261 patients showed three-year disease-free survival of 71% versus 50% with four cycles of gemcitabine-platinum started within 90 days of nephroureterectomy in pT2 to pT4 or node-positive disease (hazard ratio 0.54; 95% confidence interval 0.36 to 0.79). ^[6] Renal function falls after nephroureterectomy to about 50 mL per minute at three months, so cisplatin may need a split dose with hydration down to a GFR of 45 mL per minute, and carboplatin is used to a GFR of 30 mL per minute or above. ^[6] Platinum eligibility is based on performance status and glomerular filtration rate, as in bladder urothelial carcinoma. ^[6]

Adjuvant nivolumab and pembrolizumab have not shown clear benefit in the UTUC subgroup of their registration trials, in which UTUC made up about 25% of patients, and a network meta-analysis favours platinum chemotherapy over immune checkpoint inhibitors after surgery. ^[6] They may still be discussed with patients who are PD-L1 positive and unfit for or decline platinum therapy. ^[6]

Intravesical instillation. The rate of bladder recurrence after nephroureterectomy for UTUC is approximately 30%. ^[6] A single postoperative instillation of intravesical chemotherapy (mitomycin C or pirarubicin) given 2 to 10 days after surgery reduces bladder recurrence in the first years, in patients without a history of bladder cancer, and adverse events are rare. ^[6] A cystogram may precede instillation if extravasation is a concern. ^[6]

For metastatic disease, the standard first-line systemic options in 2026 are enfortumab vedotin plus pembrolizumab where available, or platinum-based combination chemotherapy, followed by maintenance avelumab in responders; later lines include immunotherapy, erdafitinib for tumours with FGFR alterations and antibody-drug conjugates. ^[6]

• Spontaneous haemorrhage from an angiomyolipoma, sometimes life-threatening. ^[1]
• Pain, mass effect and haematuria from large tumours.
• Misdiagnosis: unnecessary radical or partial nephrectomy when a mass believed to be cancer is in fact oncocytoma or angiomyolipoma. ^[2]
• Biopsy and surgery complications, including haematoma. ^[2]
• Everolimus toxicity (stomatitis, rash, interstitial pneumonitis) in tuberous sclerosis. ^[1]

• Local invasion, hydronephrosis and renal impairment.
• Bladder recurrence in about 30% after nephroureterectomy. ^[6]
• Perioperative complications of nephroureterectomy, including renal function decline to about 50 mL per minute at three months. ^[6]
• Metastasis to regional nodes, lung, liver and bone.
• Chemotherapy toxicity and the toxicities of immunotherapy and antibody-drug conjugates in metastatic disease. ^[6]

Most benign renal tumours have an excellent prognosis. Classical angiomyolipoma and oncocytoma do not metastasise and do not cause cancer death. ^[1] The key risk in practice is overtreatment and the risk of bleeding from large angiomyolipomas.

UTUC prognosis depends heavily on stage and grade. Low-grade, non-invasive tumours managed with kidney-sparing surgery do well but need prolonged surveillance because recurrence is common. High-risk invasive disease carries a substantially worse outcome; adjuvant platinum chemotherapy improves disease-free survival after nephroureterectomy. ^[6] The ability to give cisplatin before renal function is lost is the rationale for neoadjuvant programmes. ^[6]

There is no population screening for benign renal tumours or for renal cell carcinoma in general. ^[1] The main preventive measures for kidney cancer overall are smoking avoidance and weight reduction. ^[1] UTUC prevention consists of avoiding tobacco and aristolochic acid exposure, reviewing occupational risks and following bladder urothelial cancer surveillance protocols, because patients with bladder cancer are at risk of upper tract disease and vice versa. ^[6] Patients with Lynch syndrome need urological surveillance, although the exact protocol is best individualised. ^[5]

Pregnancy can complicate angiomyolipoma because hormonal changes may promote growth, and spontaneous bleeding has been reported. In women of childbearing age with large angiomyolipomas, active treatment is sometimes chosen pre-emptively. ^[1] Renal masses found in pregnancy are investigated with ultrasound and, where necessary, non-contrast MRI, avoiding CT radiation. UTUC in pregnancy is rare and management is multidisciplinary. ^[5]

Tuberous sclerosis presents in childhood with seizures and skin findings, and children may develop multiple renal angiomyolipomas and cysts. Regular renal imaging as part of tuberous sclerosis surveillance is standard, although local protocols differ. Genetic diagnosis of TSC1 or TSC2 is available. ^[4] Oncocytoma and UTUC are rare in children.

Small renal masses in older, frail patients may be observed, because renal cell cancer specific mortality is low in selected patients and competing causes of death dominate. ^[3] Upper tract urothelial carcinoma in older patients is treated according to overall fitness for surgery and renal function, with kidney-sparing approaches favoured when nephroureterectomy is too risky. ^[6]

Patients with tuberous sclerosis need multidisciplinary care and should be managed according to syndrome-specific surveillance guidance. ^[4] Lynch syndrome increases UTUC risk and triggers genetic referral. ^[5] Families with hereditary renal cancer, including von Hippel-Lindau, Birt-Hogg-Dube and fumarate hydratase deficiency, are managed with nephron-sparing strategies and surveillance to a 3 cm threshold in most syndromes. ^[4]

• Ultrasound is the accessible first test for a renal mass, but it cannot reliably distinguish a lipid-poor angiomyolipoma from cancer; referral of imaging and biopsy results to a regional centre prevents unnecessary nephrectomy. ^[2]
• CT and partial nephrectomy may be unavailable; many patients have an open nephrectomy, which still cures localised cancer at the cost of renal function, so refer early to a surgical centre. ^[3]
• Active surveillance can be supported by ultrasound at intervals when CT is not available, provided the patient can attend and escalate if growth or symptoms occur. ^[3]
• For UTUC, urine cytology and basic imaging (ultrasound or intravenous urography) may be the only investigations available; cystoscopy and CT urography require planning and referral. ^[5]
• Nephroureterectomy with bladder cuff is standard but requires open surgery and training; early referral improves outcomes. ^[6]
• Single-dose perioperative bladder instillation after nephroureterectomy is inexpensive and reduces bladder recurrence; systems should make it routine. ^[6]

• renal cell carcinoma
• bladder cancer
• tuberous sclerosis
• haematuria