Renal Masses: Complex Cysts, Renal Cell Carcinoma & Angiomyolipoma

Evaluating an incidental renal mass

First step. Most renal masses are now found on imaging done for another reason. A lesion that meets ultrasound criteria for a simple cyst (anechoic, thin smooth wall, posterior acoustic enhancement, no septa or solid parts) needs nothing further. Anything else is characterized with a renal-protocol CT, imaged before and after IV contrast, or with MRI; MRI or contrast-enhanced ultrasound suit patients in whom iodinated contrast is undesirable. Two findings drive decisions: enhancement (a rise of roughly ≥20 HU), which means vascularized tissue, and macroscopic fat (negative attenuation), which identifies angiomyolipoma.

Solid versus cystic. An enhancing solid mass without fat is renal cell carcinoma until proven otherwise. Cystic lesions are graded with the Bosniak classification, which predicts malignancy and dictates follow-up.

Renal cell carcinoma: biology and risk factors

Subtypes. RCC accounts for about 90% of kidney cancers. Clear cell RCC (~75%) arises from proximal tubule cells whose cytoplasm is cleared by lipid and glycogen. Papillary RCC (~10–15%) is linked to MET activation and to acquired cystic disease in dialysis patients; chromophobe RCC (~5%) arises from intercalated cells and has a good prognosis.

VHL and HIF. Nearly all clear cell tumors lose the VHL tumor suppressor on chromosome 3p. Without VHL, hypoxia-inducible factor escapes degradation and drives VEGF, PDGF and erythropoietin, explaining the tumor's vascularity, occasional erythrocytosis and response to VEGF-pathway drugs.

Risk factors. Incidence peaks at 60–70 years with a male predominance of about 2:1. Smoking is the leading modifiable factor, followed by obesity and hypertension. Acquired cystic kidney disease after years of dialysis raises risk, as do occupational trichloroethylene and cadmium.

Hereditary syndromes. Suspect one when RCC is young-onset, bilateral or multifocal. Von Hippel-Lindau disease (autosomal dominant) causes multiple clear cell RCCs and renal cysts plus CNS and retinal hemangioblastomas, pheochromocytoma and pancreatic cysts or neuroendocrine tumors; renal tumors are removed with nephron-sparing surgery once the largest reaches about 3 cm, and the HIF-2α inhibitor belzutifan can shrink them. Tuberous sclerosis (TSC1/TSC2) produces multiple angiomyolipomas, cysts and a modestly increased RCC risk. Birt-Hogg-Dubé syndrome (chromophobe or oncocytic tumors, fibrofolliculomas, lung cysts) is rarer.

Presentation and patterns of spread

Symptoms. More than half of RCCs are found incidentally. Hematuria is the most common symptom, but the classic triad of flank pain, hematuria and a palpable mass occurs in fewer than 10% and usually signals advanced disease. Fever, weight loss and night sweats accompany larger tumors, and anemia is common.

Venous invasion. RCC grows into the renal vein and IVC as tumor thrombus, sometimes reaching the right atrium, and can cause leg edema, Budd-Chiari syndrome or pulmonary emboli. Because the left gonadal vein drains into the left renal vein, a new left varicocele that does not decompress when supine suggests renal vein obstruction and warrants abdominal CT. Tumor thrombus does not preclude cure: radical nephrectomy with thrombectomy is performed.

Metastases. About 25–30% have metastases at diagnosis, spread hematogenously to lungs (cannonball nodules), bone (lytic lesions), liver, adrenal glands and brain, and recurrence can appear years after nephrectomy. Staging uses contrast CT of chest and abdomen, adding bone or brain imaging when symptoms or labs suggest spread.

Management of renal cell carcinoma

No routine biopsy. Imaging predicts malignancy so well that a solid enhancing mass in a fit patient goes straight to surgery. Biopsy is reserved for situations where it changes management: suspected lymphoma, metastasis to the kidney or abscess; small masses before ablation or active surveillance; and metastatic disease before systemic therapy.

Localized disease. Surgery is curative. Partial nephrectomy is preferred for T1 tumors (≤7 cm, especially ≤4 cm) because preserving nephrons limits later CKD and its cardiovascular risk; it is essential with bilateral tumors, a solitary kidney or VHL. Radical nephrectomy is used for large or central tumors. Small masses in elderly or frail patients can be treated with thermal ablation or followed with active surveillance, and high-risk resected clear cell RCC may receive adjuvant pembrolizumab.

Metastatic disease. RCC resists conventional chemotherapy and is relatively radioresistant. First-line treatment for clear cell disease uses checkpoint inhibitors: nivolumab plus ipilimumab, or pembrolizumab or nivolumab with a VEGF tyrosine kinase inhibitor such as axitinib, cabozantinib or lenvatinib. Other options are sunitinib, pazopanib, mTOR inhibitors (everolimus) and belzutifan; high-dose IL-2 is largely historical. Radiation palliates painful bone or brain metastases, and stereotactic body radiotherapy (SBRT) is used for oligometastatic disease.

Benign masses and upper-tract urothelial carcinoma

Angiomyolipoma. This benign tumor of thick-walled vessels, smooth muscle and fat is diagnosed on CT by macroscopic fat. Most are sporadic and solitary in middle-aged women; multiple bilateral lesions suggest tuberous sclerosis, which also causes lymphangioleiomyomatosis. The danger is spontaneous retroperitoneal hemorrhage (Wunderlich syndrome: flank pain, flank mass, hypovolemic shock), which becomes likelier at ≥4 cm and in pregnancy. Sporadic asymptomatic lesions under 4 cm are followed with imaging; larger or symptomatic lesions undergo selective arterial embolization or partial nephrectomy, and embolization is first-line for acute bleeding. In tuberous sclerosis, the mTOR inhibitor everolimus is first-line for asymptomatic, growing lesions over 3 cm, and nephrectomy is avoided to preserve renal function.

Oncocytoma. About 5% of renal masses, this benign tumor arises from intercalated cells and consists of large eosinophilic cells packed with mitochondria. A central stellate scar is suggestive but unreliable, and it cannot be confidently separated from chromophobe RCC on imaging or even biopsy, so most are removed by partial nephrectomy and need no further treatment.

Urothelial carcinoma of the renal pelvis. Upper-tract urothelial carcinoma presents with painless gross hematuria, sometimes with clot colic. Risk factors are smoking, aromatic amines (dye and rubber industries), cyclophosphamide, phenacetin abuse, aristolochic acid (Balkan nephropathy, some herbal remedies) and Lynch syndrome. CT urography shows a filling defect, and ureteroscopy with biopsy plus urine cytology confirms it. High-grade disease is treated with radical nephroureterectomy with a bladder cuff, followed by cystoscopic surveillance because bladder recurrences are common.

Painless gross hematuria in an adult smoker needs both CT urography for the upper tracts and cystoscopy for the bladder.