History and exam
Key diagnostic factors
common
uncommon
flank pain
Other diagnostic factors
uncommon
nonspecific systemic symptoms
Included in a spectrum of paraneoplastic presentations of RCC, and occur in up to 20% of patients.[18] May include fever, weight loss, sweats, pallor, cachexia, myoneuropathy.
signs of hepatic dysfunction
Included in a spectrum of paraneoplastic presentations of RCC.[18] Includes ascites, hepatomegaly, and spider angiomata.
myoneuropathy
Included in a spectrum of paraneoplastic presentations of RCC.[18]
lower limb edema
Often suggestive of inferior vena cava involvement, but not a common presentation.
scrotal varicocele
RCC is a cause of varicocele in a very small proportion of men.[67]
dermatologic manifestation (hereditary syndromes)
Patients may present with dermatologic signs of hereditary syndrome. Patients with Birt-Hogg-Dube syndrome may have dermatologic papules; and hereditary leiomyomatous patients may have skin fibromas.
vision loss (von Hippel-Lindau)
Patients with the hereditary syndrome von Hippel-Lindau may present with vision loss and retinal angiomatosis detected on fundoscopy.
Risk factors
strong
smoking
Has been consistently shown to be the most well-established modifiable risk factor for RCC in both men and women.[27][30] It is implicated in 20% to 30% of renal cancers in men, and 10% to 20% in women.[26]
In one study, smokers with more than 22.5 pack-years of exposure had a greater than 50% increased risk of RCC, compared with those who never smoked.[42] The overall relative risk of RCC is 1.31 for all (current and former) smokers.[43]
male sex
The incidence in males is twice that of females in most populations studied.[22]
age over 55 years
residence in developed countries
RCC has a higher incidence and prevalence in Europe and North America.[27]
non-Hispanic American Indian/Alaska Native ethnicity
obesity
Associated with increased risk for RCC.[27][30] In one study, individuals with a BMI ≥35 had a 71% increased risk of RCC compared with normal weight individuals (BMI <25).[42]
There is some evidence to suggest that patients with RCC with obesity may have improved survival outcomes compared with patients with RCC without obesity.[44] The association of body composition with clinical outcomes is being evaluated in a multicenter prospective cohort study.[45]
hypertension
positive family history of RCC
A positive family history of renal cancer carries a 2.8- to 4.3-fold increased risk for RCC.[47]
Familial non-syndromic RCC is suspected when two or more relatives have RCC and there are no features to suggest an underlying "syndromic cause."[33] Early-onset tumors and/or multiple/bilateral tumors increase suspicion of familial RCC, and genetic testing is usually performed.[33] Cases without an identifiable genetic cause are likely to be genetically heterogeneous.[33]
history of hereditary syndromes
Familial RCC is usually inherited in an autosomal dominant manner and accounts for 3% to 5% of RCC.[48][49]
Von Hippel-Lindau syndrome is the most common syndrome associated with clear cell RCC.[33] Type 1 papillary kidney cancers have mutations in the mesenchymal-epithelial transition factor (MET) gene and type 2 as part of hereditary leiomyomatosis and kidney cell cancer having fumarate hydratase (FH) mutations.[33] Chromophobe and oncocytic kidney cancers are predominantly associated with Birt-Hogg-Dubé syndrome, which has a folliculin (FLCN) mutation.[33] Tuberous sclerosis may be associated with early-onset RCC, but RCC is rare in this condition and renal lesions are most commonly angiomyolipomas.[33]
weak
asbestos/cadmium exposure
obstetric history/estrogen exposure
Reproductive factors (e.g., parity, age at first birth) have been associated with risk for renal cell carcinoma; however, study findings are not universally consistent.[54][55][56][57]
There is evidence to suggest that hormone replacement therapy is inversely associated with risk for renal cell carcinoma in women.[58] One cohort study found that women who reported hysterectomy appeared to be at increased risk for renal cell carcinoma.[54]
pelvic radiation
A small increase in RCC has been found in patients who have received ionizing radiation therapy.[26]
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