Renal cell carcinoma (RCC), which arises from renal tubular epithelium, is the most common cause of renal malignancy in adults. While a fraction of cases of RCC occur in association with hereditary disorders, most cases are sporadic. Important risk factors for RCC include smoking, acquired cystic disease of the kidney, nephrolithiasis, and chronic acetaminophen use. Clinical features of RCC include hematuria, flank pain, a flank mass, anemia, and weight loss. Patients may also present with paraneoplastic manifestations such as hypercalcemia and hypertension. The most important initial test is a contrast CT of the abdomen. The treatment of choice is surgical resection. RCC is notoriously resistant to classical chemotherapeutic agents. Early stage RCC with tumor growth limited to the kidney has a very good prognosis.
- Prevalence: most common malignancy of the renal parenchyma (70% of renal cancers in adults are renal cell carcinoma)
- Incidence 
Epidemiological data refers to the US, unless otherwise specified.
- Most renal cell carcinomas (RCCs) occur sporadically.
- Approx. 4% of renal cell carcinomas are associated with hereditary factors.
- Both forms show structural alterations of the short arm of chromosome 3 (3p) and subsequent alterations of the VHL gene.
Risk factors for sporadic RCC 
- Associated conditions
- Substance exposure
Hereditary renal cell carcinomas 
- : Approx. 40% of patients with VHL syndrome develop renal cell carcinomas (usually clear cell RCC).
- Inherited autosomal dominant condition caused by a mutation in the folliculin (FLCN) gene on chromosome 17
- Characterized by the following symptoms:
- Hereditary leiomyomatosis and renal cancer syndrome (HLRCC)
- Hereditary papillary renal cell carcinoma (HPRCC)
- Succinate dehydrogenase deficiency: autosomal dominant condition associated with paragangliomas, pheochromocytomas, and renal cell carcinoma.
- Constitutional symptoms
- Symptoms caused by primary tumor 
- Symptoms of local spread and metastatic disease: see “Complications” below
The classical triad of renal cell carcinoma consists of hematuria, flank pain, and a palpable flank mass. However, only 10–15% of patients present with all three components of the triad and > 25% present with one or more atypical symptoms related to paraneoplastic syndromes and/or disseminated disease. 
TNM classification (8th Edition, 2017)
|Overview of TNM classification|
AJCC staging (8th Edition, 2017)
|Overview of AJCC stages|
|Stage I|| |
|Stage II|| |
|Stage III|| |
|Stage IV|| |
Evaluation of RCC
Abdominal CT scan with contrast: best initial test
- Distorted renal outline and stretched renal calyces
- Renal lesion(s) with thickened irregular walls, variable enhancement, and calcification
- Renal ultrasound: renal lesion(s) with variable echogenicity
Evaluation of metastatic disease
- Chest CT/MRI
- Bone scan: indicated for patients with bone pain and ↑ ALP
- Abdominal ultrasound
Laboratory tests 
|Overview of the most important types of renal cell carcinoma |
|Clear cell renal cell carcinoma||Non-clear cell renal cell carcinomas|
|Papillary (chromophilic) RCC||Chromophobe RCC||Oncocytic RCC||Collecting duct carcinoma (Bellini duct carcinoma)|
|Relative frequency|| || || || || |
|Cell of origin|| || |
|Etiology|| || |
|Macroscopic appearance|| |
|Microscopic appearance|| || |
|Prognosis|| || || |
Malignant renal masses
- Renal cell carcinoma
- Metastasis from extrarenal tumors
- renal pelvis (∼ 8% of renal tumors) of the
- Other rare primary malignancies
All renal masses > 1 cm in size are presumed to be renal cell carcinoma and treated as such.
Benign renal masses
- Renal abscess
- (e.g., polycystic kidney disease)
- Metanephric adenoma
- Granulomatous renal disease (e.g., renal tuberculosis, xanthogranulomatous pyelonephritis)
- Definition: benign renal tumors that arise from smooth muscle, and mature fat cells and consist of blood vessels,
- Clinical features
- Treatment: Surgical resection of the tumor is indicated for angiomyolipomas that measure > 4 cm in diameter.
- Definition: benign epithelial tumor arising from the intercalated tubular cells in the collecting duct
- Clinical features
- Prognosis: Oncocytomas are not invasive, but they may transform into a malignant oncocytic RCC.
The differential diagnoses listed here are not exhaustive.
Surgical resection 
- Approach: open, robotic, or laparoscopic surgery
- Localized disease
- In some cases even for large tumors
Targeted therapy 
Tyrosine kinase inhibitors
Cabozantinib: small molecule receptor tyrosine kinase inhibitor used in the treatment of RCC and HCC
- Mechanism of action: inhibition of certain subtypes of VEGFR and various tyrosine kinases
- Indications: advanced RCC and sorafenib-refractory HCC
- Adverse effects include gastrointestinal upset, palmar-plantar erythrodysesthesia, and hypertension.
- Associated with rare cases of gastrointestinal fistulas and perforation
Multi-target tyrosine kinase inhibitors
- Anti-VEGF antibodies: bevacizumab
- Anti-PD-1 antibodies
- Anti-PD-L1 antibodies: avelumab
- CTLA-4 antibodies: ipilimumab
- Renal artery embolization
- Radiation therapy is not typically used to treat RCC due to resistance. 
- High resistance rate against chemotherapy because tumor cells express MDR-1 (multidrug resistance protein-1)
Complications caused by paraneoplastic syndromes 
- Secondary hypercortisolism: due to ectopic ACTH release
- Secondary polycythemia: due to ectopic erythropoietin (EPO) secretion
- Hypertension: due to the release of renin
- Hypercalcemia: due to the release of PTHrP (parathyroid hormone-related protein)
- Leukemoid reaction: due to bone marrow stimulation
- Limbic encephalitis 
Complications caused by local spread
- : caused by involvement of the IVC
Complications caused by metastatic disease
- Pulmonary metastases: most common site of metastases
- Bone metastases: second most common site of metastases
- Epidemiology: RCC accounts for 25 to 42% of all reported AA amyloidosis cases caused by solid organ malignancies.
- Clinical features
We list the most important complications. The selection is not exhaustive.
Survival of kidney cancer patients
- Overall prognosis is determined by the anatomic extent of the disease (stage of cancer at diagnosis) and the histopathology of the tumor.
- Targeted therapies have significantly prolonged survival time.
- Early stage RCC with tumor growth limited to the kidney generally has a good prognosis.
|5-year survival of kidney cancer patients |
|SEER stage||Description||5-year survival rate|
|All stages combined|| || |
Motzer score 
- Used to determine prognosis of patients with stage IV (distant) disease
- A point is assigned for each of the following criteria.
- Based on the resulting score, the prognosis of the metastatic RCC patient is estimated.
- High scores are associated with a poorer prognosis.
|Karnofsky performance status|| |
|< 80%: 1 point|
|> 80%: 0 points|
|Hemoglobin level|| |
♀ < 12.0 g/dL
|< 12.0 g/dL: 1 point|
|> 12.0 g/dL: 0 points|
|♂ < 13.5 g/dL||< 13.5 g/dL: 1 point|
|> 13.5 g/dL: 0 points|
|↑ LDH (> 1.5 times the upper normal limit)||> 420 U/L||> 420 U/L: 1 point|
|< 420 U/L: 0 point|
|↑ Serum calcium||> 10 mg/dL (> 2.5 mmol/L)||> 10 mg/dL (> 2.5 mmol/L): 1 point|
|< 10 mg/dL (< 2.5 mmol/L): 0 points|
|Time from diagnosis to systemic treatment||< 1 year||< 1 year: 1 point|
|> 1 year: 0 points|
|Motzer score interpretation|
|0|| || |
|1–2|| || |
|≥ 3|| || |