Renal Cell Carcinoma
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- Renal cell carcinoma (RCC) arises from the parenchyma of the kidney (as opposed to urothelial cancer, which arises from the renal pelvis/calyces). According to SEER, there is estimated to be 63,990 new cases (including renal pelvis) in 2017, making up 3.8% of all cancers diagnosed. It is the eighth most common cancer diagnosed in the United States.
- Characterized by obscure and varied presentations, including paraneoplastic syndromes, vascular findings, and uncommon metastatic sites
- Metastatic disease landing sites commonly include bones, lung, and regional lymph nodes.
- Early, aggressive surgical management provides the best opportunity for cure.
- System(s) affected: renal/urologic
- Predominant age: patients in 5th to 7th decades; median age at diagnosis is 64 years.
- Male to female 2:1
- Age-adjusted incidence is increasing 3% per year, likely due in part to increased detection as an incidental finding on imaging studies.
- >60% are detected as an incidental finding.
- The incidence of RCC is rising, whereas the death rate from RCC has concurrently decreased (SEER).
- The rate of metastatic disease increases with the size of the renal mass.
- 1.1% (1 to 2 cm), 3.3% (2 to 3 cm), 6% (3 to 4 cm)
Etiology and Pathophysiology
- Most common site of metastatic disease is lung.
- Pathogenesis: loss of von Hippel-Lindau (VHL) gene resulting in decreased degradation of hypoxia-inducible factor (HIF) which in turn leads to increased expression of angiogenic growth factors (vascular endothelial growth factor [VEGF] and platelet-derived growth factor [PDGF])
- Five distinct subtypes
- Clear cell: 70–80%; proximal tubule, solitary
- Papillary renal cell (previously termed chromophilic): 10–15%; proximal tubule; tumors tend to be bilateral and multifocal; type 1 and more aggressive type 2 variant
- Chromophobe: 3–5%; intercalated cells; tend to have a less aggressive course
- Medullary: <1%; typically affects younger patients; most are at an advanced stage with metastases at time of diagnosis; occurs almost exclusively in patients with sickle cell trait
- Collecting duct: <1%, aggressive disease with high mortality
- 2–3% of cases are familial, with several autosomal dominant syndromes described.
- Oncogenes localized to the short arm of chromosome 3 may have etiologic implications. Chromosome 3p12-p26 is specific for clear cell RCC.
- Multiple hereditary types of RCC have been established, although VHL remains the most common, predisposing the clear cell RCC and vascular lesions.
- Hereditary papillary RCC is an autosomal dominant form of disease associated with multifocal papillary renal tumors and a 5:1 male predominance; no extrarenal manifestations
- Other familial RCC include Birt-Hogg-Dubé (BHD) syndrome, hereditary leiomyomatosis and RCC (HLRCC), tuberous sclerosis.
- Prior diagnosis of RCC—risk increases to 2–4% for a metachronous RCC in absence of familial disease.
- Smoking, active and passive
- Hypertension (Antihypertensive medications are not independently associated with RCC.)
- End-stage renal failure: Patients on hemodialysis have an increased risk of RCC.
- Acquired renal cystic disease
- Tuberous sclerosis
- Family history of RCC
- Heavy-meat and high-fat dairy products
- Lower socioeconomic status
- Heavy metal exposure (cadmium, lead)
- Environmental toxin exposure (asbestos, petroleum by-products, chlorinated solvents)
- Complex renal cyst
- Bosniak classification
- I: simple cyst
- II: low risk of future malignant transformation
- IIF: small risk of malignant transformation with follow-up warranted
- III and IV: 50–100% risk of malignancy
- Smoking may contribute to 1/3 of all cases.
- Diet heavy in fruit and vegetables may be protective.
Commonly Associated Conditions
- VHL disease: 30–45% of these patients develop clear cell tumors.
- Tuberous sclerosis: associated primarily with angiomyolipoma and clear cell tumors
- HLRCC: cutaneous and uterine leiomyomas; more aggressive type II papillary RCC. 15–30% develops RCC.
- BHD: associated with oncocytomas and chromophobe RCC, benign cutaneous lesions, lung cysts, and associated risk of pneumothorax
- Sickle cell trait: With few exceptions, renal medullary tumor is seen in young African American males with sickle cell trait.
- Adult polycystic kidney disease
- Renal cystic disease from chronic renal failure