History and exam
Key diagnostic factors
common
presence of risk factors
Risk factors include smoking, male sex, age over 55 years, obesity, hypertension, positive family history of renal cancer, and history of hereditary syndrome.
uncommon
flank pain
Other diagnostic factors
uncommon
non-specific 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 oedema
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.[66]
dermatological manifestation (hereditary syndromes)
Patients may present with dermatological signs of hereditary syndrome. Patients with Birt-Hogg-Dube syndrome may have dermatological 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 multicentre 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 tumours and/or multiple/bilateral tumours 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/oestrogen 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 ionising radiotherapy.[26]
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