Clear cell renal cell carcinoma is a type of kidney cancer. It develops from tiny tubes inside the kidney called tubules. Clear cell renal cell carcinoma is the most common type of kidney cancer found in adults. Many clear cell renal cell carcinomas grow slowly and have a good outlook. However, some tumors may behave more aggressively, especially if they contain certain aggressive features, such as sarcomatoid or rhabdoid cells, or if the tumor has spread outside the kidney.
by Trevor A. Flood, MD FRCPC
June 14, 2025
What are the symptoms of clear cell renal cell carcinoma?
Many people with clear cell renal cell carcinoma do not experience noticeable symptoms. Often, these tumors are found during imaging tests done for other reasons. When symptoms occur, they can include:
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Blood in the urine, which can appear red, pink, or brown.
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Pain or discomfort in the back or side of the abdomen.
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Feeling a lump or swelling in the abdomen.
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Fever without a clear cause.
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Unintended weight loss.
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Fatigue or feeling generally unwell.
If the tumor has spread (metastasized) to other areas, symptoms depend on which part of the body is affected.
What causes clear cell renal cell carcinoma?
Most cases of clear cell renal cell carcinoma happen by chance. Usually, there’s no specific cause or identifiable reason why these tumors form. However, certain inherited genetic conditions can increase a person’s risk of developing clear cell renal cell carcinoma at a younger age and sometimes involve multiple tumors.
Genetic conditions associated with clear cell renal cell carcinoma
Some people inherit genetic conditions that increase their risk of kidney tumors. One important genetic syndrome associated with clear cell renal cell carcinoma is called Birt-Hogg-Dubé syndrome. People with this condition often develop multiple kidney tumors, including clear cell renal cell carcinoma. They also typically have benign skin tumors and cysts in their lungs.
How is clear cell renal cell carcinoma usually diagnosed?
Clear cell renal cell carcinoma is often discovered by accident during imaging tests like ultrasound, CT, or MRI scans of the abdomen. These tests reveal the tumor as a mass within the kidney.
Your doctor may recommend a biopsy, which involves removing a small sample of the tumor for examination under a microscope. Often, however, the doctor might suggest removing the entire tumor without doing a biopsy first.
What does clear cell renal cell carcinoma look like under the microscope?
Under the microscope, clear cell renal cell carcinoma is characterized by large, round cells. These cells often have clear-looking interiors, giving the tumor its name. The tumor cells form large groups, separated by many small blood vessels that supply the tumor with blood. This appearance helps pathologists confirm the diagnosis of clear cell renal cell carcinoma.
What is the WHO/ISUP grade, and why is it important?
The WHO/ISUP grade is a scoring system used by pathologists to describe how abnormal tumor cells appear under the microscope. This grading helps predict the aggressiveness of a tumor and its likelihood of spreading.
The WHO/ISUP system grades clear cell renal cell carcinoma from Grade 1 to Grade 4:
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Grade 1: Tumor cells look very similar to normal kidney cells, with small, round nuclei (cell centers).
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Grade 2: Tumor cells have slightly larger, more irregular nuclei.
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Grade 3: Tumor cells have obviously enlarged, irregular nuclei that are easy to spot under a microscope.
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Grade 4: Tumor cells appear extremely abnormal, bizarre, and irregularly shaped. This grade also includes tumors with aggressive features called sarcomatoid or rhabdoid cells.
Higher-grade tumors (Grades 3 and 4) grow more rapidly, are more aggressive, and have a higher likelihood of metastasizing (spreading) than lower-grade tumors (Grades 1 and 2).
What are sarcomatoid cells and why are they important?
Sarcomatoid cells are tumor cells that have changed in shape and behavior, becoming more aggressive. Normally, clear cell carcinoma cells are round, but sarcomatoid cells become long and spindle-shaped. Tumors containing sarcomatoid cells often spread more easily, making treatment more challenging.
What are rhabdoid cells and why are they important?
Rhabdoid cells are tumor cells that resemble muscle cells. Like sarcomatoid cells, rhabdoid cells indicate a more aggressive tumor. Their presence is associated with a greater chance of the tumor spreading to other parts of the body.
What is tumor necrosis?
Necrosis refers to areas within the tumor where cells have died. This usually occurs when the tumor grows quickly and outpaces its blood supply. Tumor necrosis is associated with more aggressive tumors and a less favorable outlook.
What does tumor extension mean, and why is it important?
Tumor extension describes whether and how far the tumor has grown beyond the kidney into nearby tissues or organs, such as surrounding fat, large blood vessels, or the adrenal gland. Your pathology report will clearly state whether the tumor has extended beyond the kidney. Tumors that extend into nearby tissues have a higher risk of spreading and may require additional treatment.
What is a surgical margin, and why is it important?
A surgical margin refers to the healthy tissue surrounding the tumor that is removed during surgery. Pathologists carefully examine these margins to see if tumor cells are present at the edges of the tissue removed.
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Negative margin: No tumor cells are present at the tissue edge. This suggests that the entire tumor was successfully removed, lowering the chance it will return.
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Positive margin: Tumor cells are found at the tissue edge. This means there might be cancer cells left in the body, which could require additional surgery or treatment.
In a partial nephrectomy (where only part of the kidney is removed), margins include the kidney tissue and surrounding fat at the area of removal. In a radical nephrectomy (where the entire kidney is removed), the margins typically include the surrounding fat, the ureter (the tube connecting the kidney to the bladder), and nearby blood vessels. Your pathology report will explain the margin status clearly.
What does lymphovascular invasion mean?
Lymphovascular invasion means that tumor cells have entered small blood or lymph vessels. Blood vessels carry blood throughout the body, and lymph vessels carry a fluid called lymph, connecting to lymph nodes. If tumor cells enter these vessels, the cancer can spread to other parts of the body. The presence of lymphovascular invasion is an important finding that may influence your treatment and monitoring.
Why are lymph nodes examined, and what do the results mean?
Lymph nodes are small immune organs throughout your body that help fight infection. Tumor cells sometimes spread to lymph nodes through lymph vessels. During surgery, nearby lymph nodes may be removed and examined to check for cancer spread.
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Negative lymph nodes: No tumor cells were found in the lymph nodes examined.
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Positive lymph nodes: Tumor cells were found in the lymph nodes examined. The presence of cancer cells in lymph nodes indicates a higher chance of cancer spreading further, possibly requiring additional treatments such as chemotherapy or immunotherapy.
Your pathology report will clearly state the number of lymph nodes examined, their location, and whether any contained cancer cells.
What is extranodal extension?
Extranodal extension means that cancer cells found inside a lymph node have broken through the node’s outer capsule into surrounding tissues. This finding is important because it indicates a higher risk of tumor recurrence or spread, and may influence your doctor’s decisions regarding additional treatments.
Pathologic staging (TNM system) for clear cell renal cell carcinoma
Your doctor uses the TNM staging system to describe the severity of your tumor. This system helps your healthcare team understand how advanced the tumor is by looking at three important factors. These factors include the size of the tumor and how far it has grown (T), whether cancer cells have spread to nearby lymph nodes (N), and whether the cancer has spread to distant parts of the body (M). Knowing the TNM stage helps your doctor plan the best treatment and estimate your prognosis (outlook).
Tumor stage (T):
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T1: The tumor is 7 cm or smaller and fully inside the kidney.
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T2: The tumor is larger than 7 cm but still completely within the kidney.
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T3: The tumor has grown into the surrounding fat or a large vein attached to the kidney.
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T4: The tumor extends outside the kidney through a protective barrier (Gerota’s fascia) or into nearby organs, such as the adrenal gland.
Lymph node stage (N):
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N0: No cancer cells in the lymph nodes.
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N1: Cancer cells found in one or more lymph nodes.
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NX: No lymph nodes were removed or examined.
Metastatic stage (M):
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M0: Cancer has not spread to distant body parts.
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M1: Cancer has spread to distant areas, like the lungs or liver.
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MX: Not enough information to determine if cancer has spread to distant body parts.
Higher stage numbers generally mean the tumor is more advanced and may need additional treatments.
Examination of the non-tumor kidney tissue
Pathologists also examine the healthy kidney tissue surrounding the tumor. They also check for other conditions, such as those caused by high blood pressure (arterionephrosclerosis) or diabetes (diabetic nephropathy). Any findings will be included in your pathology report.
Questions to ask your doctor
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Can you clearly explain my tumor’s grade and stage?
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Are sarcomatoid or rhabdoid cells present in my tumor, and what does this mean?
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What are the surgical margin results, and will I need additional treatments?
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Were my lymph nodes clear, or do I need further treatments due to lymph node involvement?
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What follow-up tests or monitoring will I need?
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What are the chances my tumor could return or spread?
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Should I consider genetic testing or counseling?
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Are there lifestyle changes I can make to improve my overall health?
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