Kidney cancer

1. Basic concepts: what is a tumor

A tumor is a mass or lump formed by tissue with abnormal growth. In the kidney, as in other organs, masses can be benign or malignant. The key difference for the student is that a benign tumor has no metastatic capacity, whereas a malignant tumor can invade tissues, involve neighboring structures, and produce distant metastases.

2. Renal cystic lesions

2.1 Simple renal cysts. These are the lesions most frequently found in the kidney. They can be single or multiple, and their frequency increases with age. In practice, they often appear as incidental findings during an ultrasound or CT ordered for another reason. A simple cyst has thin walls, fluid content, no thick septations, and no solid component; when it meets these characteristics it does not usually require treatment, only an explanation to the patient and follow-up only if the context justifies it.

2.2 Parapelvic cysts. A subtype of simple cysts that originate near the renal sinus. They can mimic dilation of the urinary tract, so the main differential diagnosis is hydronephrosis. Unlike hydronephrosis, they do not necessarily represent obstruction of the urinary tract; when the image is unclear, CT or MRI may be required to define the anatomy.

2.3 Complex renal cyst. It may have an irregular shape, septa, calcifications, wall thickening, or solid areas. These features raise the suspicion of malignancy and require the lesion to be classified more precisely: not every renal cyst is innocent.

2.4 Bosniak classification. It sorts cystic renal masses according to their imaging characteristics and their risk of malignancy (the updated version incorporates CT and MRI criteria).

Category	Practical interpretation
Bosniak I	Benign simple cyst. Requires no treatment.
Bosniak II	Benign or very low-risk cystic lesion. Generally requires no treatment.
Bosniak IIF	Probably benign lesion, but requires imaging follow-up.
Bosniak III	Indeterminate lesion with significant risk of malignancy. May require surgery or surveillance depending on the patient.
Bosniak IV	Lesion with an enhancing solid or nodular component. High suspicion of malignancy and usually treatment.

2.5 Polycystic kidney disease. A hereditary disorder in which multiple cysts develop, mainly within the kidneys; as they grow, the kidneys enlarge and may lose function over time. It may be accompanied by liver cysts and manifestations in other organs. Complications include hypertension, pain, hematuria, infections, stone disease, and kidney failure. In most cases there is a hereditary basis, although spontaneous mutations can also occur.

3. Benign solid tumors

3.1 Renal oncocytoma. A solid tumor with benign clinical behavior; it accounts for approximately 3-7% of solid renal tumors. The practical problem is that on imaging it can be difficult to distinguish from renal carcinoma, so many lesions that later turn out to be oncocytomas end up being treated surgically as suspicious masses. Percutaneous biopsy can help in some cases, although it does not always resolve all doubts.

3.2 Renal angiomyolipoma. A benign neoplasm of mesenchymal origin composed of adipose tissue, smooth muscle, and blood vessels; it can be sporadic or associated with tuberous sclerosis. When it is small, asymptomatic, and smaller than 4 cm, it can usually be observed. The main risk of large angiomyolipomas is spontaneous bleeding (Wunderlich syndrome): sudden flank pain, a mass or abdominal pain, and signs of hypovolemic shock in severe cases. If the size is larger, or there are symptoms or a risk of bleeding, selective embolization or surgery may be considered.

4. Renal carcinoma: overview

Renal cell carcinoma is the most common kidney cancer in adults. It often runs for years without symptoms and is discovered incidentally on an ultrasound, CT, or MRI performed for another reason. It accounts for approximately 2-3% of solid tumors in adults; it is more common in men (ratio close to 1.5:1), with higher incidence between ages 60 and 70. The lifetime risk of developing it is estimated at 1.3-1.8%.

4.1 Risk factors:

• Smoking.
• Advanced age.
• Male sex.
• Obesity and elevated body mass index.
• Hypertension.
• Chronic kidney disease or history of kidney disease.
• Genetic factors and family history.
• Prolonged exposure to certain drugs or toxins, depending on the clinical context.

4.2 Genetics and tumor biology. In clear cell renal carcinoma, alteration of the VHL gene (chromosome 3p), a tumor suppressor gene, is common. When it is inactivated by mutation or methylation, oxygen, nutrient, and energy sensing pathways are altered, with overexpression of hypoxia-inducible factors (especially HIF) that favors the production of angiogenic factors such as VEGF. This is why this tumor tends to be hypervascular, and why many modern systemic treatments target angiogenesis pathways or immune checkpoints.

4.3 Hereditary disease. It accounts for a minority of cases (approx. 5-8%). It should be suspected with presentation at a young age, family history, bilateral or multifocal lesions, or associated tumors in other organs. A kidney tumor in a young patient or with bilateral lesions should not be interpreted as an isolated case until hereditary syndromes have been ruled out.

5. Histologic types, grade, and staging

5.1 Main histopathologic entities:

Histologic type	Approx. frequency	Relevant characteristics
Clear cell	70-80%	The most common subtype. Yellow, hypervascular tumors related to the VHL/HIF/VEGF pathway.
Papillary	10-15%	Papillary architecture. Type 1 and type 2; type 2 tends to be more aggressive.
Chromophobe	5%	Originates in the distal tubule. Generally a better prognosis than clear cell.
Others	Less common	Rare variants with variable behavior.

5.2 Grade of differentiation. It is based on nuclear characteristics (nuclear shape and size, presence of the nucleolus, features of aggressiveness). In practical terms, grades 1-2 are considered low grade and 3-4 high grade; it has prognostic value because of its association with the risk of progression and recurrence.

5.3 Staging. TNM staging describes anatomic extent: T (primary tumor), N (regional lymph node involvement), and M (distant metastasis). The most frequent metastatic sites are the lung, bone, liver, adrenal glands, and brain, although renal carcinoma can also metastasize to unusual sites.

6. Clinical presentation

The way it presents has changed a great deal with the widespread use of abdominal imaging: today most kidney tumors are diagnosed incidentally. When there are symptoms, they may be due to local tumor growth, hemorrhage, paraneoplastic syndromes, or metastases. The classic triad of flank pain, hematuria, and palpable mass is now uncommon and, when it appears, usually indicates advanced disease. Other possible findings: weight loss, new-onset right varicocele, lower limb edema, bone pain, persistent cough, or constitutional symptoms.

6.1 Paraneoplastic syndromes. Renal carcinoma can produce renin, erythropoietin, prostaglandins, and vitamin D-related metabolites:

Manifestation	Mechanism or interpretation
Hypercalcemia	Can cause nausea, anorexia, fatigue, and decreased reflexes.
Hypertension	May be related to renin production or vascular compression.
Polycythemia	Erythropoietin production.
Stauffer syndrome	Non-metastatic hepatic dysfunction associated with renal carcinoma.

7. Diagnosis

7.1 Diagnostic imaging. Diagnosis is primarily by imaging. Ultrasound is usually the entry point, especially to distinguish simple cystic lesions from solid masses. Contrast-enhanced CT with intravenous contrast is the central study to characterize the lesion and to assess enhancement, local extension, venous involvement, lymph nodes, and neighboring organs. Gadolinium MRI is useful when CT is inconclusive, to avoid radiation, in cases of allergy to iodinated contrast, or to evaluate tumor thrombus in the renal vein or vena cava. PET-CT is not routine for initial staging.

Study	Main utility
Ultrasound	Distinguishes a simple cyst from a solid mass; useful as a first study.
Abdominal CT with contrast	Characterization and local staging; enhancement, extension, and vena cava.
MRI with gadolinium	Characterizes indeterminate lesions and venous thrombus; alternative to CT in selected cases.
Chest CT	Evaluation of pulmonary metastases according to risk and stage.
PET-CT	Not routinely recommended for primary staging.

7.2 Percutaneous biopsy. It is not indicated for all patients with a renal mass. It can be useful in indeterminate lesions, candidates for active surveillance, before ablative therapies, and in metastatic disease when histologic confirmation is needed before systemic treatment. If the result will not change management (for example, because the patient will undergo surgery anyway), it may not be necessary. In cystic masses it has a lower yield, unless there is a clear solid component.

8. Localized disease

The mainstay of treatment is surgery. The main options are partial nephrectomy, radical nephrectomy, active surveillance, and ablative therapies in selected cases.

8.1 Partial nephrectomy. It aims to remove the tumor while preserving the rest of the renal parenchyma. It is especially important when kidney preservation is technically feasible, and in chronic kidney disease, a solitary kidney, bilateral tumors, or genetic syndromes; it is also considered in Bosniak III-IV cystic lesions when active treatment is indicated and the anatomy allows it. Whenever it is oncologically safe and technically possible, preserving nephrons helps reduce the risk of long-term renal deterioration.

8.2 Radical nephrectomy. Removal of the entire kidney together with the tumor. It is indicated for bulky tumors, technically complex lesions, poorly functioning kidneys, locally advanced disease, or when a partial nephrectomy is neither safe nor appropriate. In tumors with extension into the renal vein or vena cava, surgery may require thrombectomy and planning at experienced centers.

8.3 Active surveillance. It may be considered in elderly patients, those with multiple comorbidities, a high Charlson index, chronic kidney disease, or small low-risk tumors (especially <4 cm). The decision depends on the balance between oncologic risk, life expectancy, renal function, and patient preferences.

8.4 Ablative therapies. Cryoablation or radiofrequency ablation, in selected small tumors, especially in patients who are not good surgical candidates. Before an ablation, it is usually recommended to obtain a histologic diagnosis by biopsy.

9. Metastatic disease

It requires a multidisciplinary approach: surgery in selected cases, systemic treatments, palliative radiotherapy for symptomatic metastases, and supportive measures.

9.1 IMDC. A model that helps stratify risk in metastatic renal carcinoma, classifying patients as favorable, intermediate, or poor risk, and guiding the selection of systemic treatment.

9.2 Cytoreductive nephrectomy. It may be considered as part of a multimodal strategy in selected patients, especially with a symptomatic primary tumor, good performance status, and favorable- or intermediate-risk disease. It should not be indicated automatically for all metastatic patients.

9.3 Systemic treatment. It is based mainly on two large groups:

Group	Examples	Central idea
Tyrosine kinase inhibitors	Axitinib, sunitinib, pazopanib, lenvatinib, cabozantinib	Block signals related to VEGF and tumor angiogenesis.
PD-1/PD-L1 inhibitors	Pembrolizumab, nivolumab	Help T lymphocytes recognize and attack the tumor.
Anti-CTLA-4	Ipilimumab	Increases activation and proliferation of effector T cells.

Combination regimens are now common (for example, immunotherapy with checkpoint inhibitors + antiangiogenics). The choice depends on IMDC risk, patient characteristics, comorbidities, tumor burden, symptoms, and availability.