- Clinical science
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.
- Most common malignancy of the renal parenchyma (85% of renal cancers in adults are RCC)
- Sex: ♂ > ♀ (∼ 2:1)
- Age of onset: 60–80 years
- Ethnicity: slightly higher incidence in black populations in the US
Epidemiological data refers to the US, unless otherwise specified.
Most renal cell carcinomas occur sporadically. However, approx. 4% of renal cell carcinomas are associated with hereditary factors. In both forms, sporadic and hereditary RCCs, structural alterations of the short arm of chromosome 3 (3p) and subsequent alterations of the VHL gene are commonly found.
Risk factors for sporadic renal cell carcinoma
- Certain pre-existing conditions
- Exposure to certain toxins
Hereditary renal cell carcinomas
- Birt-Hogg-Dube syndrome
- Hereditary papillary renal cell carcinoma (HPRCC)
- Hereditary leiomyomatosis and renal cancer syndrome (HLRCC, Reed's syndrome) : 15% of the patients diagnosed with leiomyomas develop type 2 papillary RCC.
- Succinate dehydrogenase deficiency
- Renal cell carcinomas are adenocarcinomas that usually arise from the epithelial cells of the proximal convoluted tubule.
- Clear cell RCC is the most common histological variant (∼ 80% of all cases).
|Type of RCC||Relative frequency||Cell of origin||Cytogenetics||Histology||Prognosis|
|Clear cell RCC||∼ 80%||Proximal convoluted tubule||Mutation of the VHL gene on chromosome 3p|| || |
|Papillary (chromophilic) RCC||∼ 10%||Trisomy 7, trisomy 17, and loss of Y chromosome|| || |
|Chromophobic RCC||∼ 5%||Intercalated cells of the cortical collecting duct||Hypodiploidy|| || |
|Oncocytic RCC||∼ 5%||Unknown|| || |
|Collecting duct carcinoma (Bellini duct carcinoma)||∼ 1%||Medullary collecting duct||Unknown|| |
A sarcomatoid pattern (containing foci of high-grade spindle cells), which can occur in any type of RCC, is associated with a poor prognosis.
- Spread of renal cell carcinoma
- Hematuria is the most common presenting symptom (> 40% of cases).
- Anemia (common; ∼ 30–90% of cases): pallor, lethargy
- Dragging/colicky flank pain (∼ 40% of cases)
- Potentially palpable renal mass (∼ 25% of cases)
- Constitutional symptoms: weight loss; (∼ 30% of cases), fatigue, night sweats; , fever (∼ 20% of cases)
The classical triad of renal cell carcinoma consists of hematuria, flank pain, and a palpable flank mass. However, only 5–10% 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.
- Hypertension (∼ 20% of cases)
- Hypercalcemia (∼ 15% of cases)
- Polycythemia (∼ 5% of cases) , leukemoid reaction
- Secondary hypercortisolism
- Stauffer's syndrome: non-metastatic hepatic dysfunction characterized by elevated liver enzymes (esp. alkaline phosphatase) and clotting abnormalities
- Limbic encephalitis: memory loss, psychosis, depression
- (3–5% of cases): nephrotic syndrome, primary adrenal insufficiency, hepatosplenomegaly, malabsorption
- Symptoms of local spread
- Symptoms of metastatic disease
TNM classification (7th Edition, 2010)
|T1||Tumor ≤ 7 cm in greatest dimension, limited to the kidney (T1a: < 4 cm; T1b: 4–7 cm)|
|T2||Tumor > 7 cm in greatest dimension, limited to the kidney (T2a: 7–10 cm; T2b: > 10 cm)|
|T4||Tumor invades beyond the Gerota fascia (including contiguous extension into the ipsilateral adrenal gland)|
|N1||Metastasis in one regional lymph node(s)|
|N2||Metastasis in multiple regional lymph node(s)|
AJCC staging (7th Edition, 2010)
|Stage III||T3 and/or N1|
|Stage IV||T4 and/or N2 and/or M1|
Evaluation of RCC
Best initial test: abdominal CT scan with contrast
- Distorted renal outline and stretched renal calyces
- Renal lesion(s) with thickened irregular walls, variable enhancement, and calcification (∼ 30% of cases)
- Renal ultrasound : renal lesion(s) with variable echogenicity
- IVU and renal arteriography were performed in the past but have now been replaced by abdominal contrast CT scan and MR angiography respectively.
- Best initial test: abdominal CT scan with contrast
- Evaluation of metastatic disease
- Urinalysis: hematuria
- Hb levels and CBC
- ↑ AST, ALT, and/or ALP
- Percutaneous renal biopsy is generally not recommended.
Common differential diagnoses for renal masses in adults include:
- Malignant masses
- Benign masses
Renal cell carcinoma is the most common cause of a small renal mass (< 4 cm) in adults. If the mass is less than 1 cm in size and asymptomatic, a watch and wait approach is recommended. All renal masses > 1 cm in size are presumed to be renal cell carcinoma and treated as such!
- Definition: benign renal tumors that arise from perivascular epithelioid cells and consist of blood vessels, smooth muscle, and mature fat cells
- Mean age of onset: 43 years
- Sex: ♀ > ♂ (4:1)
- Clinical features
- Imaging usually provided the diagnosis
- Percutaneous biopsy may be required if imaging is inconclusive
- Treatment: Surgical resection; of the tumor is indicated for angiomyolipomas that measure more than 4 mm in diameter.
Oncocytoma is a benign epithelial tumor. Histologically, an oncocytoma consists of large, acidophilic, mitochondria-rich tumor cells (so-called oncocytes) without perinuclear clearing (vs. chromophobic RCC); . An oncocytoma is not confined to the kidneys and may develop in the thyroid gland, pancreas, or the pituitary gland.
- Definition: benign tumor arising from the intercalated tubular cells
- If tumor increases in size → suspicious for malignant transformation in RCC → nephrectomy
- Often resected in order to exclude RCC
- Prognosis: Oncocytomas are not invasive, but they may transform into a malignant oncocytic RCC.
The differential diagnoses listed here are not exhaustive.
Treatment of choice: surgical resection of the tumor via open, robotic, or laparoscopic surgery . Depending on the extent of the tumor, the following surgical procedures are performed:
- Stage I: cryoablation, thermal ablation, partial nephrectomy , or simple nephrectomy
- Stage II–IV: radical nephrectomy
- Patients who are unfit for surgery should be monitored for tumor growth and may be treated palliatively with:
- Arterial embolization
- External beam radiotherapy
- Immunomodulatory and/or targeted therapy
Chemotherapy is not used to treat RCC because RCC is highly resistant to chemotherapeutic agents, with a response rate of only 15–30%! This occurs because tumor cells express MDR-1 (multidrug resistance protein-1).
- Patients who are not fit for surgery: abdominal CT/MRI within 6 months to determine if the tumor is growing, and thereafter annually
Patients who have been treated surgically
- Stage I disease
- Patients who have been treated with ablation: abdominal CT/MRI at 3 and 6 months, and thereafter annually for 5 years
- Patients who have been treated with partial or simple nephrectomy: abdominal CT/MRI annually for 3 years
- Stage II–IV: abdominal CT/MRI every 6 months after surgery for the first 3 years, and thereafter annually for the next 2 years
- Stage I disease
The overall prognosis is determined by the anatomic extent of the disease (stage of cancer at diagnosis) and the histopathology of the tumor. Early stage RCC with tumor growth limited to the kidney generally has a good prognosis.
- Histopathology: Collecting duct carcinomas and RCC with a sarcomatoid appearance on histology are associated with a poor prognosis.
5-year survival rates of RCC based on AJCC staging
- Stage I: 81%
- Stage II: 74%
- Stage III: 53%
- Stage IV: 8%
- In < 5% of cases: spontaneous regression of metastasis after tumor resection
- Motzer score is used to determine the prognosis of patients with stage IV 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.
|Karnovsky performance status (PS)|| |
|Low hemoglobin level|| |
♂ < 12.0–15.5 g/dL
♀ < 13.5–17.5 g/dL
|Increased lactate dehydrogenase (LDH)||> 420 U/L|
|Increased serum calcium||> 10 mg/dL (> 2.5 mmol/L)|
|Time from diagnosis to systemic treatment||< 1 year|
Increased awareness and screening (e.g., ultrasound) of high-risk patients in recent years has led to earlier tumor detection and improved the prognosis of RCC!