Diagnostic Evaluation


Many renal masses remain asymptomatic until the late disease stages. More than 50% of RCCs are detected incidentally by non-invasive imaging investigating various non-specific symptoms and other abdominal diseases [89,100]. The classic triad of flank pain, visible haematuria, and palpable abdominal mass is rare (6-10%) and correlates with aggressive histology and advanced disease [41,101].

Paraneoplastic syndromes are found in approximately 30% of patients with symptomatic RCCs [102]. Some symptomatic patients present with symptoms caused by metastatic disease, such as bone pain or persistent cough [103].

a.Physical examination

Physical examination has a limited role in RCC diagnosis. However, the following findings should prompt radiological examinations:

  • palpable abdominal mass;
  • palpable cervical lymphadenopathy;
  • non-reducing varicocele and bilateral lower extremity oedema, which suggests venous involvement.

b.Laboratory findings

Commonly assessed laboratory parameters are serum creatinine, glomerular filtration rate (GFR), complete cell blood count, erythrocyte sedimentation rate, liver function study, alkaline phosphatase, lactate dehydrogenase (LDH), serum corrected calcium [104], coagulation study, and urinalysis. For central renal masses abutting or invading the collecting system, urinary cytology and possibly endoscopic assessment should be considered in order to exclude urothelial cancer.

Split renal function should be estimated using renal scintigraphy in the following situations [105,106]:

  • when renal function is compromised, as indicated by increased serum creatinine or significantly decreased GFR;
  • when renal function is clinically important – e.g., in patients with a solitary kidney or multiple or bilateral tumours.

Renal scintigraphy is an additional diagnostic option in patients at risk of future renal impairment due to comorbid disorders.

2.Imaging investigations

Most renal tumours are diagnosed by abdominal US or CT performed for other medical reasons [100]. Renal masses are classified as solid or cystic based on imaging findings.

a.Presence of enhancement

With solid renal masses, the most important criterion for differentiating malignant lesions is the presence of enhancement [107]. Traditionally, US, CT and MRI are used for detecting and characterising renal masses. Most renal masses are diagnosed accurately by imaging alone. Contrast-enhanced US can be helpful in specific cases [108-110].

b.Computed tomography or magnetic resonance imaging

Computed tomography or MRI is used to characterise renal masses. Imaging must be performed before, and after, administration of intravenous contrast material to demonstrate enhancement. In CT imaging, enhancement in renal masses is determined by comparing Hounsfield units (HUs) before, and after, contrast administration. A change of fifteen, or more, HUs demonstrates enhancement [111]. Computed tomography or MRI allows accurate diagnosis of RCC, but cannot reliably distinguish oncocytoma and fat-free AML from malignant renal neoplasms [77,112-114]. Abdominal CT provides information on [115]:

  • function and morphology of the contralateral kidney [116];
  • primary tumour extension;
  • venous involvement;
  • enlargement of locoregional LNs;
  • condition of the adrenal glands and other solid organs.

Abdominal contrast-enhanced CT angiography is useful in selected cases in case detailed information on the renal vascular supply is needed [117,118].

If the results of CT are indeterminate, CEUS is a valuable alternative to further characterise renal lesions [7].

Magnetic resonance imaging may provide additional information on venous involvement if the extent of an inferior vena cava (IVC) tumour thrombus is poorly defined on CT [119-122].

Magnetic resonance imaging is indicated in patients who are allergic to intravenous CT contrast medium and in pregnancy without renal failure [120,123]. Advanced MRI techniques such as diffusion-weighted and perfusion-weighted imaging are being explored for renal mass assessment [124].

For the diagnosis of complex renal cysts (Bosniak IIF-III) MRI may be preferable. The accuracy of CT is limited in these cases, with poor sensitivity (36%) and specificity (76%; κ = 0.11); MRI had 71% sensitivity and 91% specificity (κ = 0.64). Contrast-enhanced US showed high sensitivity (100%) and specificity (97%), with a negative predictive value of 100% (κ = 0.95) [81].

In younger patients who are worried about the radiation exposure of frequent CT scans, MRI may be offered as alternative although only limited data exist on a correlation between diagnostic radiation exposure and development of secondary cancers [125].

c.Other investigations

Renal arteriography and inferior venacavography have a limited role in the work-up of selected RCC patients. In patients with any sign of impaired renal function, an isotope renogram and total renal function evaluation should be considered to optimise treatment decision making [105,106]. Positron-emission tomography (PET) is not recommended [7,126].

d.Radiographic investigations to evaluate RCC metastases

Chest CT is accurate for chest staging [94,95,127-129]. There is a consensus that most bone metastases are symptomatic at diagnosis; thus, routine bone imaging is not generally indicated [127,130,131]. However, bone scan, brain CT, or MRI may be used in the presence of specific clinical or laboratory signs and symptoms [130,132,133].

e.Bosniak classification of renal cystic masses

This classification system classifies renal cysts into five categories, based on CT imaging appearance, to predict malignancy risk [134,135].

3. Renal tumour biopsy

Percutaneous renal tumour biopsy can reveal histology of radiologically indeterminate renal masses and can be considered in patients who are candidates for AS of small masses, to obtain histology before ablative treatments, and to select the most suitable medical and surgical treatment strategy in the setting of metastatic disease [136-141].

Renal biopsy is not indicated for comorbid and frail patients who can be considered only for conservative management (watchful waiting) regardless of biopsy results. Due to the high diagnostic accuracy of abdominal imaging, renal tumour biopsy is not necessary in patients with a contrast-enhancing renal mass for whom surgery is planned.

Percutaneous sampling can be performed under local anaesthesia with needle core biopsy and/or fine needle aspiration (FNA). Biopsies can be performed with US or CT guidance, with a similar diagnostic yield [139,142]. Eighteen-gauge needles are ideal for core biopsies, as they result in low morbidity and provide sufficient tissue for diagnosis [136,140,143]. A coaxial technique allowing multiple biopsies through a coaxial cannula should always be used to avoid potential tumour seeding [136,140].

Core biopsies are preferred for the characterisation of solid renal masses while a combination with FNA can improve accuracy [144-146]. An SR and meta-analysis of the diagnostic performance and complications of renal tumour biopsy was performed by the Panel. Fifty-seven articles with a total of 5,228 patients were included in the analysis. Needle core biopsies were found to have better accuracy for the diagnosis of malignancy compared with FNA [146]. Other studies showed that solid pattern, larger tumour size and exophytic location are predictors of a diagnostic core biopsy [136,139,142].

In experienced centres, core biopsies have a high diagnostic yield, specificity, and sensitivity for the diagnosis of malignancy. The above-mentioned meta-analysis showed that sensitivity and specificity of diagnostic core biopsies for the diagnosis of malignancy are 99.1% and 99.7%, respectively [146]. However, 0-22.6% of core biopsies are non-diagnostic (8% in the meta-analysis) [137-143,147]. If a biopsy is non-diagnostic, and radiologic findings are suspicious for malignancy, a further biopsy or surgical exploration should be considered. Repeat biopsies have been reported to be diagnostic in a high proportion of cases (83-100%) [136,148-150].

Accuracy of renal tumour biopsies for the diagnosis of tumour histotype is good. The median concordance rate between tumour histotype on renal tumour biopsy and on the surgical specimen of the following PN or RN was 90.3% in the pooled analysis [146].

Assessment of tumour grade on core biopsies is challenging. In the pooled analysis the overall accuracy for nuclear grading was poor (62.5%), but significantly improved (87%) using a simplified two-tier system (high vs. low grade) [146].

The ideal number and location of core biopsies are not defined. However, at least two good quality cores should be obtained, and necrotic areas should be avoided to maximise diagnostic yield [136,139,151,152]. Peripheral biopsies are preferable for larger tumours, to avoid areas of central necrosis [153]. In cT2 or greater renal masses, multiple core biopsies taken from at least four separate solid enhancing areas in the tumour were shown to achieve a higher diagnostic yield and a higher accuracy to identify sarcomatoid features, without increasing the complication rate [154].

Core biopsies of cystic renal masses have a lower diagnostic yield and accuracy and are not recommended alone, unless areas with a solid pattern are present (Bosniak IV cysts) [136,139,146].

Combined FNA and core biopsies can provide complementary results, especially for complex cystic lesions [140,147,148,155,156].

Overall, percutaneous biopsies have a low morbidity [146]. Tumour seeding along the needle tract is anecdotal. Spontaneously resolving subcapsular/perinephric haematomas are reported in 4.3% of cases in a pooled analysis, but clinically significant bleeding is unusual (0-1.4%; 0.7% in the pooled analysis) and generally self-limiting [146].

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