- 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 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
- Hereditary papillary renal cell carcinoma (HPRCC)
- Hereditary leiomyomatosis and renal cancer syndrome (HLRCC, Reed's syndrome)
- 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.
- Anemia (common): pallor, lethargy
- Dragging/colicky flank pain
- Potentially palpable renal mass
- Constitutional symptoms: weight loss; , fatigue, night sweats, fever
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.
- Paraneoplastic syndromes
- Symptoms of local spread
- Symptoms of metastatic disease
TNM classification (8th Edition, 2017)
|T4||Tumor extends beyond the Gerota fascia (including contiguous extension into the ipsilateral adrenal gland)|
|N0||No metastasis in regional lymph node(s)|
|N1||Metastasis in regional lymph node(s)|
|M0||No distant metastasis|
AJCC staging (8th Edition, 2017)
|Stage I|| |
|Stage II|| |
|Stage III|| |
|Stage IV|| |
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
- Renal ultrasound : renal lesion(s) with variable echogenicity
- 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 smooth muscle, and mature fat cells and consist of blood vessels,
- 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 cm 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
- 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 (see ), the following surgical procedures are performed:
- 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).
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.
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!