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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Oncology

      Renal Cell Carcinoma Workup

      Updated: Mar 21, 2023
      • Author: Kush Sachdeva, MD; Chief Editor: E Jason Abel, MD  more...
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      Workup

      Approach Considerations

      With the increasing utilization of imaging studies, renal cell carcinoma (RCC) is increasingly detected incidentally, as a suspicious mass on abdominal computed tomography (CT) or ultrasound. [17] Fewer patients present with symptomatic disease (eg, gross hematuria, flank mass or pain).

      RCC is remarkable for the frequent occurrence of paraneoplastic syndromes, including hypercalcemia, erythrocytosis, and nonmetastatic hepatic dysfunction (ie, Stauffer syndrome). Thus, laboratory studies in the evaluation of RCC should include a workup for paraneoplastic syndromes.

      A number of imaging modalities are used to evaluate and stage suspected renal cancer, including the following:

      • CT of the abdomen, preferably with pelvic CT
      • Magnetic resonance imaging (MRI), if venous involvement is suspected or the patient cannot tolerate contrast
      • Ultrasonography
      • Chest CT scan or chest x-ray
      • Excretory urography
      • Renal arteriography
      • Venography
      • Bone scan if bone metastasis is suspected or alkaline phosphatase level is elevated
      • Brain CT or MRI if patient has clinical manifestations suggesting brain metastases

      Determining whether a space-occupying renal mass is benign or malignant can be difficult. Imaging studies should be tailored to enable further characterization of renal masses, so that nonmalignant tumors can be differentiated from malignant ones.

      Contrast-enhanced CT scanning has become the imaging procedure of choice for diagnosis and staging of renal cell cancer and has virtually replaced excretory urography and renal ultrasonography. Ultrasonographic examination can be useful in evaluating questionable cystic renal lesions if CT imaging is inconclusive. Large papillary renal tumors are frequently undetectable by renal ultrasonography.

      Excretory urography is not used frequently in the initial evaluation of renal masses because of its low sensitivity and specificity. A small- to medium-sized tumor may be missed by excretory urography.

      Renal arteriography is not used in the evaluation of a suspected renal mass as frequently now as it was in the past. When inferior vena cava involvement is suspected, either inferior venacavography or magnetic resonance angiography (MRA) is used. MRA is currently the preferred imaging technique. Knowledge of inferior vena cava involvement is important in planning the vascular aspect of the operative procedure.

      Positron emission tomography (PET) imaging remains controversial in kidney cancer. Currently, PET is not considered a standard part of the diagnosis of kidney cancer or in follow-up for evidence of relapse after nephrectomy. [18] PET has a better sensitivity for detecting metastatic lesions than for determining the presence of cancer in the renal primary site.

      When clinically indicated, bone scans are used both in inital workup and follow-up. A bone scan is recommended for patients with pain or an elevated alkaline phosphatase level. [18]

      For more information, see Renal Cell Carcinoma Imaging.

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      Initial Laboratory Studies

      The following are initial laboratory studies in the evaluation of suspected renal cell carcinoma (RCC):

      • Urinalysis (UA) with urine cytology (if central lesion)
      • Urine cytology (if central lesion is present, to evaluate for urothelial carcinoma)
      • Complete blood cell (CBC) count with differential
      • Electrolytes
      • Kidney function tests
      • Liver function tests (LFTs): Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      • Serum calcium
      • Other tests as indicated by the patient’s presenting signs and symptoms.
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      Computed Tomography and Magnetic Resonance Imaging

      Contrast-enhanced computed tomography (CT) scanning has become the imaging procedure of choice for diagnosis and staging of renal cell cancer and has virtually replaced excretory urography and renal ultrasonography. In most cases, CT imaging can differentiate cystic masses from solid masses and supplies information about lymph node, renal vein, and inferior vena cava involvement.

      The 2017 American Urological Association (AUA) guideline for the management of the clinical T1 renal mass recommends a high-quality cross-sectional CT or MRI, first without and then with intravenous contrast if kidney function is adequate. The objectives are as follows. [19] :

      • Rule out angiomyolipoma radiographically if possible
      • Evaluate for locally invasive features
      • Study the involved anatomy
      • Determine the status of the uninvolved kidney and its vasculature

      The National Comprehensive Cancer Network (NCCN) guidelines for kidney cancer recommend the following as part of the initial workup [18] :

      • Abdominal/pelvic CT or abdominal MRI with or without contrast, depending on renal insufficiency
      • Chest imaging
      • Brain MRI, if clinically indicated

      The NCCN guideline recommends abdominal MRI to assess suspected tumor involvement in the inferior vena cava, or as an alternative to CT for renal mass detection and staging in cases where the use of contrast is contraindicated because of allergy or renal insufficiency. [18]

      A study by Sauk et al concluded that multidetector CT imaging characteristics may aid in identifying differences at the cytogenic level among patients with clear cell renal cell carcinomas. Imaging features that proved significant included degree of attenuation and presence of calcifications. [20]

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      Percutaneous Biopsy

      Percutaneous cyst puncture and fluid analysis is used in the evaluation of potentially malignant cystic renal lesions detected by ultrasonography or computed tomography imaging.

      According to the AUA management guideline, a renal mass core biopsy via a percutaneous approach, with or without fine needle aspiration, is indicated in patients for whom the results might affect approach to treatment. Biopsy is especially appropriate in patients with clinical or radiographic evidence of lymphoma, abscess, or metastasis. [19]

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      Histology

      Renal cell carcinoma (RCC) has the following common subtypes, in addition to other rare subtypes:

      • Clear cell or conventional (75% of cases)
      • Papillary (10-15%)
      • Chromophobe (5%)
      • Collecting duct (< 1%)
      • Translocation associated
      • Tubulocystic
      • Unclassified 

      Clear cell carcinoma is characterized by unusually clear cells with a cytoplasm rich in lipids and glycogen, and it is most likely to show 3p deletion. Papillary renal cell carcinomas are divided into type 1 and type 2. Papillary tumors are more likely to be bilateral and multifocal and may have trisomy 7 and/or trisomy 17. Chromophobe carcinoma is characterized by large polygonal cells with pale reticular cytoplasm, and it does not exhibit 3p deletion.

      Collecting duct carcinoma is an unusual variant characterized by a very aggressive clinical course. This disease tends to affect younger patients and may present as local or widespread advanced disease. These cells can have three different types of growth patterns: acinar, sarcomatoid, and tubulopapillary.

      Sarcomatoid de-differentiation may occur with several subtypes and is associated with a poor prognosis.

      Go to Clear Cell Renal Cell Carcinoma and Sarcomatoid and Rhabdoid Renal Cell Carcinoma for complete information on these topics.

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      Procedures

      The following may be performed to rule out urothelial carcinoma:

      • Cystoscopy and ureteroscopy of central lesions
      • Biopsy of central mass lesions 
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      Staging

      The following are briefly discussed in this section:

      • The Robson modification of the Flocks and Kadesky system
      • The tumor, nodes, and metastases (TNM) classification
      • The American Joint Committee on Cancer (AJCC) staging system

      Robson staging system

      The Robson modification of the Flocks and Kadesky system is uncomplicated and is commonly used in clinical practice. This system was designed to correlate stage at presentation with prognosis and is as follows:

      • Stage I – Tumor confined within capsule of kidney
      • Stage II – Tumor invading perinephric fat but still contained within the Gerota fascia
      • Stage III – Tumor invading the renal vein or inferior vena cava (A), regional lymph node involvement (B), or both (C)
      • Stage IV – Tumor invading adjacent viscera (excluding ipsilateral adrenal) or distant metastases

      TNM classification

      The TNM classification is endorsed by the AJCC. The major advantage of this system is that it clearly differentiates individuals with tumor thrombi from those with local nodal disease. In the Robson system, stage III disease includes both inferior vena caval involvement (stage IIIA) and local lymph node metastases (stage IIIB). Although patients with Robson stage IIIB renal carcinoma have greatly decreased survival rates, the prognosis for patients with stage Robson IIIA renal carcinoma is not markedly different from that for patients with Robson stage I or II renal carcinoma. The TNM classification system is delineated below.

      Primary tumors (T) are defined as the following:

      • TX – Primary tumor cannot be assessed
      • T0 – No evidence of primary tumor
      • T1 – Tumor 7 cm or smaller in greatest dimension, limited to the kidney: T1a,  ≤4 cm; T1b,  4-7 cm 
      • T2 – Tumor larger than 7 cm in greatest dimension, limited to the kidney: T2a, 7-10 cm; T2b, > 10 cm 
      • T3 – Tumor extends into major veins or invades adrenal gland or perinephric tissues but not beyond the Gerota fascia: T3a, tumor invades adrenal gland or perinephric tissues but not beyond the Gerota fascia; T3b, tumor grossly extends into the renal vein(s) or vena cava below the diaphragm; T3c, tumor grossly extends into the renal vein(s) or vena cava above the diaphragm
      • T4 – Tumor invading beyond the Gerota fascia

      Regional lymph node (N) classification is not affected by laterality and is defined as follows:

      • NX – Regional lymph nodes cannot be assessed
      • N0 – No regional lymph node metastasis
      • N1 – Metastasis in regional lymph node(s)

      Distant metastasis (M) is defined as the following:

      • M0 – No distant metastasis
      • M1 – Distant metastasis

      AJCC staging system

      The AJCC stages are as follows:

      • Stage I – T1, N0, M0
      • Stage II – T2, N0, M0
      • Stage III – T1-2, N1, M0 or T3a-c, N0-1, M0
      • Stage IV – T4; or any T, N2, M0; or any T, any N, M1

      The division of patients with renal cell carcinoma into low-, intermediate-, and high-risk groups with or without metastases may be useful in choosing appropriate therapy for these individuals. [2, 21]

      For more information, see Renal Cell Carcinoma Staging.

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