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Diagnosis[edit]
An accurate diagnosis may be difficult to establish given that the early stages of renal cancer are asymptomatic. Renal tumours are often discovered incidentally on radiologic imaging performed for an unrelated reason. RCC is twice more frequent in males than in females (2:1 ratio) with typical presentations around the sixth and seventh decades of life. Renal cancers are graded on a scale of 1 to 4, based upon the TMN criterion. The prevalence of various radiological imaging procedures such as intravenous pyelography (IVP), ultrasonography, or computed tomography (CT) scanning have revolutionised the way abnormal renal masses are detected for early stage renal cancer in patients who are asymptomatic.
The first steps taken in order to diagnose this condition are observing any of the signs and symptoms, and an anamnesis (the detailed medical review of past health state) to evaluate any risk factors. Based on the symptoms presented, a range of biochemical tests (using blood and/or urine samples) are generally also considered as part of screening process to provide sufficient quantitative analysis of any differences in electrolytes, renal and liver function, and blood clotting times. Upon physical examination, palpation of the abdomen may reveal the presence of a mass or an organ enlargement.[1]
Although this disease lacks characterisation in the early stages of tumour development, considerations based on diverse clinical manifestations, as well as resistance to radiation and chemotherapy are important. The main diagnostic tools for detecting renal cell carcinoma are ultrasound, Computed Tomography (CT) scanning and Magnetic Resonance Imaging (MRI) of the kidneys.[2] Tumour staging (using the TMN staging system) of RCC are determined mainly with CT. If the ultrasound shows a mass or cyst, a subsequent CT or MRI with intravenous contrast is the optimal test for diagnosis and staging.
Laboratory Tests[edit]
Laboratory tests are generally conducted when the patient presents signs and symptoms that may be characteristic of kidney impairment. They are not primarily used to diagnose kidney cancer, due to its asymptomatic nature and are generally found incidentally during tests for other illnesses such as gallbladder disease.[3] In other words, these cancers are not detected usually because they do not cause pain or discomfort when they are discovered. Laboratory analysis can provide an assessment on the overall health of the patient and can provide information in determining the staging and degree of metastasis to other parts of the body (if a renal lesion has been identified) before treatment is given.
Urinalysis (Urine analysis)[edit]
The presence of blood in urine is a common presumptive sign of renal cell carcinoma. The haemoglobin of the blood causes the urine to be rusty, brown or red in colour. Alternatively, urinalysis can test for sugar, protein and bacteria which can also serve as indicators for cancer. A complete blood cell count can also provide additional information regarding the severity and spreading of the cancer.[4]
Complete Blood Cell (CBC) count with differential[edit]
The CBC test provides a quantified measure of the different cells in the whole blood sample from the patient. Such cells examined for in this test include red blood cells (erythrocytes), white blood cells (leukocytes) and platelets (thrombocytes). A common sign of renal cell carcinoma is anaemia whereby the patient exhibits deficiency in red blood cells.[5] CBC tests are vital as a screening tool for examination the health of patient prior to surgery. Inconsistencies with platelet counts are also common amongst these cancer patients and further coagulation tests, including ESR, Prothrombin Time, Activated Partial Thromboplastin Time should be considered.
Blood Chemistry Tests[edit]
Blood chemistry tests are conducted if renal cell carcinoma is suspected as cancer has the potential to elevate levels of particular chemicals in blood. For example, liver enzymes such as aspartate aminotransferase [AST] and alanine aminotransferase [ALT] are found to be at abnormally high levels.[6] The staging of the cancer can also be determined by abnormal elevated levels of calcium, which suggests that the cancer may have metastasised to the bones.[7] In this case, a doctor should be prompted for a CT scan. Blood chemistry tests also assess the overall function of the kidneys and can allow the doctor to decide upon further radiological tests.
Radiology[edit]
The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin and may be seen as a lump on the lower pelvic or abdomen region. Traditionally, 85 to 90% of solid renal masses will turn out to be RCC but cystic renal mass mass may also be due to RCC.[8] However, the advances of diagnostic modalities are able to incidentally diagnose a great proportion of patients with renal lesions that may appear to be small in size and of benign state. Ten percent of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat.[9] Deciding on the benign or malignant nature of the renal mass on the basis of its localised size is an issue as renal cell carcinoma may also be cystic. As there are several benign cystic renal lesions (simple renal cyst, hemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the radiologist to differentiate a benign cystic lesion from a malignant one.[10] The Bosniak classification system for cystic renal lesions that classifies them based specific imaging features into groups that are benign and those that need surgical resection is available.[11]
The main imaging tests performed in order to identify renal cell carcinoma are pelvic and abdominal CT scans, ultrasound tests of the kidneys (ultrasonography), MRI scan, intravenous pyelogram (IVP) or renal angiography.[12] Among these main diagnostic tests, other radiologic tests such as excretory urography, positron-emission tomography (PET) scanning, ultrasonography, arteriography, venography, and bone scanning can also used to aid in the evaluation of staging renal masses and to differentiate non-malignant tumours from malignant tumours.
Computed Tomography Scanning[edit]
Contrast-enhanced Computed Tomography (CT) scanning is a routinely used imaging procedure in determining the stage of the renal cell carcinoma in the abdominal and pelvic regions of the patient. CT scans have the potential to distinguish solid masses from cystic masses and may provide information on the localisation, stage or spread of the cancer to other organs of the patient. Key parts of the human body which are examined for metastatic involvement of renal cell carcinoma may include the renal vein, lymph node and the involvement of the inferior vena cava.[13] According to a study conducted by Sauk et al, multidetector CT imaging characteristics have applications in diagnosing patients with clear renal cell carcinoma by depicting the differences of these cells at the cytogenic level.[14]
Ultrasound or Ultrasonography[edit]
Ultrasonographic examination can be useful in evaluating questionable asymptomatic kidney tumours and cystic renal lesions if Computed Tomography imaging is inconclusive. This radiologic procedure is a safe and non-invasive which uses high frequency sound waves to generate an interior image of the body on a computer monitor. The image generated by the ultrasound can help diagnose renal cell carcinoma based on the differences of sound reflections on the surface of organs and the abnormal tissue masses. Essentially, ultrasound tests can determine whether the composition of the kidney mass is mainly solid or filled with fluid.[12]
Percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumour for the purpose of diagnosis by pathology. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient may make it unfavourable from a risk-benefit perspective.[15] However, biopsy tests for molecular analysis to distinguish benign from malignant renal tumours is of investigative interest.[15]
Magnetic Resonance Imaging[edit]
Magnetic Resonance Imaging (MRI) scans provide an image of the soft tissues in the body using radio waves and strong magnets. MRI can be used in replacement of CT if the patient exhibits an allergy to the contrast media cannot be administered.[16] [17] Sometimes prior to the MRI scan, an intravenous injection of a contrasting material called gadolinium to allow for a more detailed image. Patients on dialysis or have renal insufficiency should avoid this contrasting material as it may induce a rare, yet severe, side effect known as nephrogenic systemic fibrosis.[18] A bone scan or brain imaging is not routinely performed unless signs or symptoms suggest potential metastatic involvement of these areas. MRI scans should also be considered to evaluate tumour extension which has grown in major blood vessels, including the vena cava, in the abdomen. MRI can be used to observe the possible spread of cancer to the brain or spinal cord should the patient present symptoms that suggest this might be the case.
Intravenous pyelogram[edit]
Intravenous pyelogram (IVP) is a useful procedure in detecting the presence of abnormal renal mass in the urinary tract. This procedure involves the injection of a contrasting dye into the arm of the patient. The dye travels from the blood stream and into the kidneys which in time, passes into the kidneys and bladder. This test is not necessary if a CT or MRI scan has been conducted.[19]
Renal Angiography[edit]
Renal angiography uses the same principle as IVP, as this type of X-ray also uses a contrasting dye. This radiologic test serves importance in diagnosing renal cell carcinoma as an aid for examining blood vessels in the kidneys. This diagnostic test relies on the contrasting agent which is injected in the renal artery to be absorbed by the cancerous cells.[20] The contrasting dye provides a clearer outline of abnormally-oriented blood vessels believed to be involved with the tumour. This is imperative for surgeons as it allows the patient’s blood vessels to be mapped prior to operation. [13]
Staging[edit]
The staging of renal cell carcinoma is the most important factor in predicting its prognosis.[21] Staging can follow the TNM staging system, where the size and extent of the tumour (T), involvement of lymph nodes (N) and metastases (M) are classified separately. Also, it can use overall stage grouping into stage I-IV, with the 1997 revision of AJCC described below:[21]
| Stage I | Tumour of a diameter of 7 cm (approx. 23⁄4 inches) or smaller, and limited to the kidney. No lymph node involvement or metastases to distant organs. |
| Stage II | Tumour larger than 7.0 cm but still limited to the kidney. No lymph node involvement or metastases to distant organs. |
| Stage III any of the following |
Tumor of any size with involvement of a nearby lymph node but no metastases to distant organs. Tumour of this stage may be with or without spread to fatty tissue around the kidney, with or without spread into the large veins leading from the kidney to the heart. |
| Tumour with spread to fatty tissue around the kidney and/or spread into the large veins leading from the kidney to the heart, but without spread to any lymph nodes or other organs. | |
| Stage IV any of the following |
Tumour that has spread directly through the fatty tissue and the fascia ligament-like tissue that surrounds the kidney. |
| Involvement of more than one lymph node near the kidney | |
| Involvement of any lymph node not near the kidney | |
| Distant metastases, such as in the lungs, bone, or brain. |
At diagnosis, 30% of renal cell carcinomas have spread to the ipsilateral renal vein, and 5-10% have continued into the inferior vena cava.[22]
Histopathology[edit]
The gross and microscopic appearance of renal cell carcinomas is highly variable. The renal cell carcinoma may present reddened areas where blood vessels have bled, and cysts containing watery fluids.[23] The body of the tumour shows large blood vessels that have walls composed of cancerous cells. Gross examination often shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, hemorrhage and scarring. In a microscopic context, there are four major histologic subtypes of renal cell cancer: clear cell (conventional RCC, 75%), papillary (15%), chromophobic (5%), and collecting duct (2%). Sarcomatoid changes (morphology showing spindle cells) can be observed within any RCC subtype. Under light microscopy, these tumour cells can exhibit papillae, tubules or nests, and are quite large, atypical, and polygonal.
Recent studies have brought attention to the close association of the type of cancerous cells to the aggressiveness of the condition. Some studies suggest that these cancerous cells accumulate glycogen and lipids, their cytoplasm appear "clear", the nuclei remain in the middle of the cells, and the cellular membrane is evident.[24] Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumour compresses the surrounding parenchyma, producing a pseudocapsule.[25]
The most common cell type exhibited by renal cell carcinoma is the clear cell, which is named by the dissolving of the cells high lipid content in the cytoplasm. The clear cells are thought to be the least likely to spread and usually respond more favourably to treatment. However, most of the tumours contain a mixture of cells. The most aggressive stage of renal cancer is believed to be the one in which the tumour is mixed, containing both clear and granular cells.[26]
The recommended histologic grading schema for RCC is the Fuhrman system (1982), which is an assessment based on the microscopic morphology of a neoplasm with haematoxylin and eosin (H&E staining). This system categorises renal cell carcinoma with grades 1, 2, 3, 4 based on nuclear characteristics. The details of the Fuhrman grading system for RCC are shown below[27]:
Table NUMBER. The Fuhrman Grading System
| Grade Level | Nuclear Characteristics |
|---|---|
| Grade I | Nuclei appears round and uniform, 10 μm; nucleoli are inconspicuous or absent. |
| Grade II | Nuclei has an irregular appearance with signs of lobe formation, 15 μm; nucleoli are evident. |
| Grade III | Nuclei appears very irregular, 20 μm; nucleoli are large and prominent. |
| Grade IV | Nuclei appear bizarre and multilobated, 20 μm or more; nucleoli are prominent. |
Nuclear grade is believed to be one of the most imperative prognostic factors in patients with renal cell carcinoma.[28] However, a study has shown that the Fuhrman grading is ideal for clear cell carcinoma but may not be appropriate chromophobe renal cell carcinomas. However, other studies believe that the staging of cancer (accomplished by CT scan) is a more favourable predictor of the prognosis of this disease.[29] In relation to renal cancer staging, the Heidelberg classification system of renal tumours was introduced in 1976 as a means of more completely correlating the histopathological features with the identified genetic defects.[30]
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