Clear Cell Renal cell Carcinoma: Understanding Your Pathology Report

Section Editor: Trevor Flood MD FRCPC
July 16, 2026

Clear cell renal cell carcinoma is a type of kidney cancer. It starts from the cells that line the tiny tubes inside the kidney called tubules, which filter the blood and make urine. It is the most common type of kidney cancer in adults, making up about 7 out of every 10 kidney cancers. The name comes from the way the tumor cells look under the microscope: the inside of each cell appears empty or “clear” because it is filled with fat and sugar that wash away when the tissue is prepared in the laboratory.

Many clear cell renal cell carcinomas are found early, grow slowly, and are cured by surgery alone. Others grow more quickly and can spread beyond the kidney. Your pathology report describes the features that separate these situations, including the grade of the tumor, its size, whether it has grown outside the kidney, and whether unusual cell types called sarcomatoid or rhabdoid cells are present.

This article will help you understand the findings in your pathology report for clear cell renal cell carcinoma, what each term means, and why it matters for your care.

What causes clear cell renal cell carcinoma?

Most clear cell renal cell carcinomas, the most common type of kidney cancer, happen by chance. In the great majority of people there is no single event or exposure that explains why the tumor developed. Almost every clear cell renal cell carcinoma begins with the same change inside the tumor cells: the loss of part of chromosome 3 and damage to a gene called VHL. The VHL gene normally acts as a brake on cell growth, and it also tells the cell to stop making the signals that build new blood vessels. When it stops working, the cell behaves as though it is starved of oxygen and switches on those signals permanently. This is why clear cell renal cell carcinomas are packed with small blood vessels, and it is the reason several of the drugs used for this cancer work by blocking blood vessel growth.

Several factors increase a person’s risk of developing this tumor:

Smoking — Long-term tobacco use roughly doubles the risk.
Obesity and high blood pressure — Both are consistently linked to a higher risk of kidney cancer.
Long-standing kidney disease — People on dialysis for many years can develop cysts in the kidneys (acquired cystic kidney disease), and tumors can arise within them.
Workplace exposures — Long-term exposure to the industrial solvent trichloroethylene is associated with clear cell renal cell carcinoma specifically.
Family history — Having a parent, brother, or sister with kidney cancer increases risk, even when no inherited syndrome is identified.

Inherited conditions associated with clear cell renal cell carcinoma

About 3 to 5 out of every 100 clear cell renal cell carcinomas develop in a person born with an inherited change in a gene. Inherited tumors are often found at a younger age, in both kidneys, or as several tumors in the same kidney.

von Hippel-Lindau (VHL) disease — The most common inherited cause of clear cell renal cell carcinoma. People born with a change in the VHL gene often develop multiple kidney tumors and kidney cysts over their lifetime, along with tumors of the blood vessels in the brain, spinal cord, and eye (hemangioblastomas), tumors of the adrenal gland (pheochromocytomas), and neuroendocrine tumors of the pancreas.
BAP1 tumor predisposition syndrome — An inherited change in the BAP1 gene is associated with clear cell renal cell carcinoma along with melanoma of the eye and skin and mesothelioma.
Constitutional chromosome 3 translocation — A rare situation in which a person is born with a rearrangement of chromosome 3. It causes clear cell renal cell carcinoma in families without any of the other features of VHL disease.
Tuberous sclerosis complex — Most often causes a noncancerous kidney tumor called angiomyolipoma, but clear cell renal cell carcinoma can also occur.

Birt-Hogg-Dubé syndrome, which is caused by a change in the FLCN gene, is another inherited condition that causes kidney tumors, along with noncancerous skin bumps and lung cysts. The kidney tumors in Birt-Hogg-Dubé syndrome are usually chromophobe renal cell carcinoma, oncocytoma, or tumors with features of both. Clear cell renal cell carcinoma is only occasionally reported in this syndrome.

What are the symptoms of clear cell renal cell carcinoma?

Most people with clear cell renal cell carcinoma, a cancer that starts in the kidney, have no symptoms at all. More than half of these tumors are now found by accident when an ultrasound, CT scan, or MRI is performed for an unrelated reason. When symptoms do occur, they may include:

Blood in the urine, which can make the urine look red, pink, or brown.
Pain or a dull ache in the back or the side of the abdomen.
A lump or fullness in the abdomen or side.
Fever without an obvious cause.
Weight loss that was not intended.
Fatigue or feeling generally unwell.
A low red blood cell count (anemia) or a high calcium level found on blood tests.

If the tumor has spread to another part of the body (a process called metastasis), the symptoms depend on where it has spread. The lungs, bones, liver, and brain are the most common sites.

How is the diagnosis made?

The diagnosis of clear cell renal cell carcinoma is made when a pathologist examines kidney tissue under a microscope. The tumor is usually first seen as a mass in the kidney on an ultrasound, CT scan, or MRI. For most kidney masses, the next step is surgery to remove the tumor rather than a needle biopsy, because imaging alone is often enough to justify removing the mass. A biopsy is more likely to be performed when the mass is small and treatment options are being weighed, when a person is not well enough for surgery, when the tumor may have spread from another organ, or when the cancer has already spread and a tissue diagnosis is needed before drug treatment can start.

Under the microscope, clear cell renal cell carcinoma is made up of rounded cells arranged in nests and sheets, separated by a delicate network of small, thin-walled blood vessels. The inside of the cells (the cytoplasm) looks clear or empty, and the cell borders are sharp, so the tumor can resemble chicken wire filled with soap bubbles. Some tumors also contain areas of pink cells, cysts, or hemorrhage. Pathologists look at the shape and size of the nucleus in each cell and at how easily the nucleoli inside the nuclei can be seen, because these features determine the grade of the tumor.

Most clear cell renal cell carcinomas can be diagnosed from their appearance alone. When the appearance overlaps with other kidney tumors, a test called immunohistochemistry may be performed. This test uses special stains to detect proteins inside the tumor cells. Clear cell renal cell carcinoma is typically positive for PAX8 (which confirms that the tumor started in the kidney), carbonic anhydrase IX or CAIX (which shows a strong, complete pattern around the edge of each cell), and CD10, and it is usually negative or only weakly positive for CK7. These stains help separate clear cell renal cell carcinoma from tumors that can look similar, including chromophobe renal cell carcinoma, clear cell papillary renal cell tumor, TFE3-rearranged renal cell carcinoma, and fumarate hydratase-deficient renal cell carcinoma. Once the diagnosis is confirmed, imaging of the chest and abdomen is used to look for spread to lymph nodes, the lungs, the liver, and the bones.

Histologic grade (WHO/ISUP grade)

Grade describes how abnormal the cells of a clear cell renal cell carcinoma look under the microscope, and it is one of the strongest predictors of how the tumor will behave. Kidney cancers are graded using the WHO/ISUP grading system, developed by the World Health Organization and the International Society of Urological Pathology. Unlike older systems, WHO/ISUP grade is based mainly on how easily the nucleoli (small round structures inside the nucleus of each cell) can be seen under the microscope. This system has replaced the Fuhrman grading system, which you may still see mentioned on older reports.

Grade 1 — Nucleoli are absent or cannot be seen, even at high magnification.
Grade 2 — Nucleoli can be seen at high magnification but are not visible at low magnification.
Grade 3 — Nucleoli are clearly visible at low magnification.
Grade 4 — The cells show extreme variation in size and shape, or there are giant cells, or the tumor contains sarcomatoid or rhabdoid cells (described in the next section).

Grades 1 and 2 are considered low grade. These tumors tend to grow slowly and are less likely to spread. Grades 3 and 4 are considered high grade. They tend to grow faster and are more likely to spread beyond the kidney. The grade is assigned from the most abnormal area of the tumor, even if that area is small. Grade helps predict how the tumor is likely to behave and is used along with stage to decide how closely a person is followed after surgery and whether additional treatment is discussed.

Sarcomatoid and rhabdoid features

Some clear cell renal cell carcinomas contain areas where the tumor cells have changed their appearance completely. These changes, called sarcomatoid and rhabdoid features, are important because they identify tumors that are more likely to grow quickly and spread, and because they change how the cancer is treated.

Sarcomatoid features — The rounded tumor cells are replaced by long, thin, spindle-shaped cells that resemble a soft tissue cancer rather than a carcinoma. Sarcomatoid change is found in about 5 out of every 100 clear cell renal cell carcinomas.
Rhabdoid features — The tumor cells become large and round with a bright pink center and an off-to-the-side nucleus, resembling muscle cells. Rhabdoid change is found in about 5 out of every 100 clear cell renal cell carcinomas and often occurs together with sarcomatoid change.

If either feature is present, the tumor is automatically WHO/ISUP grade 4, and your report will state the percentage of the tumor involved. Both features are associated with a higher risk of the cancer returning and a shorter survival. Importantly, tumors with sarcomatoid features tend to respond better than average to immunotherapy, so this finding on the report is one of the details the medical oncology team uses when discussing drug treatment.

Tumor size

Your pathology report will state the size of the clear cell renal cell carcinoma, measured in centimeters, from the tissue removed at surgery. This measurement is more accurate than the size estimated on imaging before surgery, so the two numbers may not match exactly. Size matters for two reasons: it is one of the main factors that determines the tumor stage (pT), and larger tumors are more likely to be high grade, to grow outside the kidney, and to spread. The important thresholds are 4 cm, 7 cm, and 10 cm. Tumors 4 cm or smaller that are confined to the kidney have an excellent outlook and can often be removed while leaving most of the kidney in place.

Tumor extension

Tumor extension describes whether a clear cell renal cell carcinoma has grown outside the kidney and, if so, how far. The kidney is surrounded by a layer of fat, and outside that fat is a tough envelope called Gerota’s fascia. The adrenal gland sits on top of the kidney, and the renal vein carries blood away from the kidney into the largest vein in the body, the inferior vena cava. Your pathologist examines all of these structures in the tissue removed at surgery.

The report may describe growth into the fat around the kidney (perinephric fat), into the fat in the middle of the kidney where the blood vessels enter (renal sinus fat), into the collecting system that drains urine (the pelvicalyceal system), into the renal vein or the inferior vena cava, into the adrenal gland, or through Gerota’s fascia into other organs. Growth into the renal vein or vena cava is common in this type of kidney cancer and does not by itself mean the cancer has spread to a distant organ, although it may change the surgery that is planned. Extension beyond the kidney raises the tumor stage and is associated with a higher risk of the cancer returning.

Lymphovascular invasion

Lymphovascular invasion means that cells from the clear cell renal cell carcinoma are seen inside small blood vessels or lymphatic channels within or around the tumor. Blood vessels carry blood throughout the body, and lymphatic channels carry a fluid called lymph toward the lymph nodes. Tumor cells inside these vessels can be carried to other parts of the body, so lymphovascular invasion is associated with a higher risk of the cancer returning or spreading.

Lymphovascular invasion is not the same as growth into the renal vein, which is a large named vessel and is reported separately as part of tumor extension and stage. Lymphovascular invasion does not change the pT stage on its own, but it is one of the findings your treatment team considers when deciding how closely to follow you after surgery.

Surgical margins

A margin is the cut edge of the tissue removed during surgery for clear cell renal cell carcinoma. Your pathologist examines these edges under the microscope to see whether any tumor cells reach them. Which margins are examined depends on the operation. In a partial nephrectomy, where only the tumor and a rim of surrounding tissue are removed, the margins are the kidney tissue and fat around the tumor. In a radical nephrectomy, where the whole kidney is removed, the margins include the fat around the kidney, the renal vein, the ureter (the tube carrying urine to the bladder), and the blood vessels.

Negative margin — No tumor cells are seen at the cut edge. This suggests the whole tumor was removed and is associated with a low risk of the cancer coming back in the same place.
Positive margin — Tumor cells are present at the cut edge. This means tumor cells may have been left behind, and it is associated with a higher risk of the cancer returning at that site. A positive margin is one of the findings the surgical and medical teams use when deciding whether more surgery or closer imaging follow-up should be considered.

Lymph nodes

Lymph nodes are small immune organs found throughout the body, including around the large blood vessels near the kidney. Cells from a clear cell renal cell carcinoma can travel through lymphatic channels and settle in a lymph node. Unlike many other cancers, lymph nodes are not removed routinely during kidney cancer surgery. They are usually removed only when they look enlarged on imaging or feel abnormal at the time of the operation, so many reports for this cancer will say that no lymph nodes were submitted.

If lymph nodes were removed, your report will state how many were examined, how many contained cancer, and the size of the largest deposit of tumor within a node. It may also state whether extranodal extension is present, which means that cancer cells inside a lymph node have broken through the outer capsule of the node into the surrounding tissue. Cancer in even one lymph node is an important finding, because it is associated with a substantially higher risk of the cancer returning and it places the tumor in a higher stage group.

Examination of the non-tumor kidney

When a kidney is removed for clear cell renal cell carcinoma, your pathologist also examines the kidney tissue away from the tumor. This part of the report is easy to overlook, but it describes how well the remaining kidney is likely to work after surgery. Common findings include scarring of the small blood vessels from long-standing high blood pressure (arterionephrosclerosis), damage to the filters from diabetes (diabetic nephropathy), and scarring from other chronic kidney disease. These findings do not describe the cancer. They are reported because they help predict kidney function after surgery and may lead to a referral to a kidney specialist (nephrologist).

Biomarker and molecular testing

Biomarkers are features of a tumor, usually a protein or a change in a gene, that provide information beyond the diagnosis itself. In many cancers, biomarker results decide which drug a person receives. Clear cell renal cell carcinoma is different: at the present time, no biomarker test is required before treatment for this cancer can be chosen, and most people with a tumor removed at an early stage will not have any molecular testing performed. Immunotherapy for this cancer, for example, is offered regardless of PD-L1 status, so PD-L1 testing is not routinely performed. The tests described below are performed in specific situations, most often when the cancer has spread, when an inherited condition is suspected, or when a clinical trial is being considered.

Chromosome 3p loss and VHL gene changes

Nearly every clear cell renal cell carcinoma has lost part of the short arm of chromosome 3, which contains the VHL tumor suppressor gene, and in most tumors the remaining copy of VHL is also damaged. These changes are usually somatic, which means they happened in the kidney cell during a person’s lifetime and cannot be passed on to children. Because this change is present in almost all of these tumors, finding it does not separate one patient from another, and it is not used to select treatment. It is sometimes tested for by next-generation sequencing (NGS) or by a test called FISH when the diagnosis is uncertain, in which case the result supports the diagnosis rather than guiding therapy. Understanding this pathway matters for a different reason: the loss of VHL is what drives the tumor to build new blood vessels, and it explains why drugs that block blood vessel growth and drugs that block a protein called HIF-2α are effective in this cancer.

Inherited (germline) genetic testing

Germline testing looks for a gene change a person was born with, using a blood or saliva sample rather than the tumor itself. It is offered to people with clear cell renal cell carcinoma who were diagnosed at a young age (usually 46 or younger), who have tumors in both kidneys or more than one tumor in the same kidney, who have a close relative with kidney cancer, or who have other features that suggest an inherited syndrome such as VHL disease. The genes usually tested include VHL, BAP1, SDHB, SDHC, SDHD, TSC1, TSC2, FLCN, MET, and FH, and a chromosome analysis may be added to look for a constitutional chromosome 3 translocation.

Results are reported in one of three ways: a pathogenic (disease-causing) variant, which confirms an inherited syndrome; no variant identified, which is the usual and reassuring result; or a variant of uncertain significance, which means a change was found but it is not yet known whether it matters. A pathogenic result is important for the whole family. It indicates a need for lifelong imaging of the kidneys and of the other organs the syndrome affects, and it means that close relatives can be offered testing of their own (called cascade testing) through a genetics clinic. It may also make a person eligible for a drug called belzutifan, which is approved for kidney tumors in people with VHL disease that do not need immediate surgery.

Comprehensive genomic profiling (next-generation sequencing)

Next-generation sequencing reads many genes at once from the tumor tissue. In clear cell renal cell carcinoma it is generally performed only when the cancer has spread and a clinical trial or a treatment outside the standard options is being considered. The genes most often altered, in addition to VHL, are PBRM1, SETD2, BAP1, KDM5C, and TP53. These results are not currently used to select an approved drug for this cancer, but they carry information about how the tumor is likely to behave: changes in BAP1 and TP53 are associated with higher grade tumors and a shorter survival, while changes in PBRM1 are associated with a more favorable course. Reports may state which alterations were found, that no reportable alterations were identified, or that a change of uncertain significance was detected. Your oncologist can explain whether any of the findings open the door to a clinical trial.

Mismatch repair, microsatellite instability, and tumor mutational burden

These tests identify tumors that respond to immunotherapy regardless of where the cancer started, an idea called a tumor-agnostic approval. Mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) are tested by immunohistochemistry and reported as intact or retained, which is the normal result, or as deficient (dMMR) when one or more proteins are lost. The related test for microsatellite instability is reported as stable (MSS) or high (MSI-H). Tumor mutational burden counts the number of mutations in the tumor and is reported as a number of mutations per megabase; 10 or more is considered high. Deficient mismatch repair, MSI-high, and high tumor mutational burden are all uncommon in clear cell renal cell carcinoma, but when present they make a person eligible for the immunotherapy drug pembrolizumab under approvals that apply across cancer types. A deficient mismatch repair result may also point to Lynch syndrome, an inherited condition that increases the risk of several cancers, and referral to a genetic counselor is considered when it is found.

You can learn more about the tests described here in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage of a clear cell renal cell carcinoma describes how far the cancer had grown at the time of surgery. It is written using the TNM system created by the American Joint Committee on Cancer (AJCC), currently in its 8th edition. T describes the size of the tumor and how far it has grown outside the kidney, N describes whether cancer is found in nearby lymph nodes, and M describes whether the cancer has spread to a distant part of the body. The letter “p” in front means the category was assigned by a pathologist after examining the tissue. The M category is almost always determined by imaging rather than by the pathologist, so it may not appear on your report at all.

Tumor stage (pT)

pT1a — The tumor is 4 cm or smaller and remains inside the kidney.
pT1b — The tumor is larger than 4 cm but not more than 7 cm and remains inside the kidney.
pT2a — The tumor is larger than 7 cm but not more than 10 cm and remains inside the kidney.
pT2b — The tumor is larger than 10 cm and remains inside the kidney.
pT3a — The tumor has grown into the renal vein or one of its branches, into the fat around the kidney or in the renal sinus, or into the collecting system that drains urine, but not beyond Gerota’s fascia.
pT3b — The tumor has grown into the inferior vena cava below the diaphragm.
pT3c — The tumor has grown into the inferior vena cava above the diaphragm, or into the wall of the vena cava.
pT4 — The tumor has grown beyond Gerota’s fascia, including growth into the adrenal gland on the same side.

Nodal stage (pN)

pN0 — No cancer was found in any of the lymph nodes examined.
pN1 — Cancer was found in one or more nearby lymph nodes.
pNX — No lymph nodes were removed or they could not be assessed. This is a common and expected result in kidney cancer surgery.

What is the prognosis?

Prognosis means the expected course of a disease. For clear cell renal cell carcinoma, the strongest predictor is the stage at diagnosis. In the United States, based on people diagnosed between 2015 and 2021, the five-year relative survival for kidney cancer that has not spread beyond the kidney is about 94%. When the cancer has grown into nearby structures or lymph nodes, five-year relative survival is about 76%. When the cancer has spread to distant organs, five-year relative survival is about 19%. These figures cover all kidney cancers rather than clear cell renal cell carcinoma alone, and they reflect people diagnosed several years ago; outcomes for advanced disease have improved substantially with newer drug treatments.

The features on your pathology report that are associated with a higher risk of the cancer returning include:

High WHO/ISUP grade — Grade 3 and grade 4 tumors return more often than grade 1 and grade 2 tumors.
Sarcomatoid or rhabdoid features — Either finding identifies a tumor that is more likely to spread, and the risk increases as the percentage of the tumor involved increases.
Tumor necrosis — Areas where tumor cells have died, usually because the tumor outgrew its blood supply. Necrosis found by a pathologist under the microscope is an independent sign of a higher risk of the cancer returning and is included in the risk scores below.
Larger tumor size — Risk rises across the 4 cm, 7 cm, and 10 cm thresholds.
Growth outside the kidney — Involvement of the fat around the kidney, the renal sinus, the renal vein, or the vena cava.
Lymphovascular invasion — Tumor cells within small blood or lymphatic vessels.
Positive surgical margin — Tumor cells at the cut edge of the tissue removed.
Cancer in lymph nodes — Even a single positive node is associated with a considerably higher risk.

These features are not weighed one at a time. Urologists combine stage, grade, tumor size, necrosis, and other findings into published risk scores, such as the Leibovich score, the SSIGN score, and the UISS, which estimate the chance that the cancer will return after surgery. Your treatment team uses one of these scores, along with the details on your report, to decide how often you will have imaging and whether additional drug treatment after surgery should be discussed. For people whose cancer has already spread, a separate tool called the IMDC risk model uses blood test results and the time since diagnosis rather than pathology findings.

What happens after the diagnosis?

Once clear cell renal cell carcinoma has been confirmed, the findings on your pathology report, particularly the stage, the grade, whether sarcomatoid or rhabdoid features are present, and the margin status, shape the next steps in your care. Kidney cancer is managed by a team that usually includes a urologist, a medical oncologist, a radiologist, and a pathologist, and may include a genetic counselor, a nephrologist, and a radiation oncologist.

Surgery — For most tumors confined to the kidney, surgery is the main treatment and is often curative. A partial nephrectomy removes the tumor and preserves the rest of the kidney and is generally possible for smaller tumors. A radical nephrectomy removes the whole kidney and is considered for larger tumors or tumors involving the renal vein. For some small tumors, especially in older adults or people with other health problems, active surveillance with regular imaging, or an ablation procedure that destroys the tumor with heat or cold, may be discussed instead.
Treatment after surgery (adjuvant therapy) — When the report shows a high-grade tumor, growth outside the kidney, or cancer in lymph nodes, the risk that the cancer will return is high enough that drug treatment after surgery is considered. Pembrolizumab, an immunotherapy drug, is approved for people with clear cell renal cell carcinoma at intermediate-high or high risk of recurrence after surgery, and it has been shown to help people live longer. In June 2026, the combination of pembrolizumab with belzutifan (a drug that blocks HIF-2α) was also approved in the same setting, based on a trial showing that adding belzutifan further reduced the risk of the cancer returning. Whether either option is appropriate depends on the risk category calculated from your pathology report.
Treatment for cancer that has spread — Advanced clear cell renal cell carcinoma is usually treated with a combination of drugs given first: two immunotherapy drugs together (ipilimumab and nivolumab), or an immunotherapy drug combined with a drug that blocks blood vessel growth (such as pembrolizumab with axitinib, nivolumab with cabozantinib, or pembrolizumab with lenvatinib). Belzutifan is approved for people whose cancer has grown after treatment with both an immunotherapy drug and a drug that blocks blood vessel growth. Chemotherapy is not effective in this cancer and is not used. Surgery or radiation may still be considered for a single site of spread.
Follow-up — Because clear cell renal cell carcinoma can return years after surgery, follow-up includes imaging of the abdomen and chest on a schedule set by the risk score, along with blood tests of kidney function. If the non-tumor kidney showed damage from diabetes or high blood pressure, a referral to a kidney specialist may be arranged.
Genetic assessment — If you were diagnosed young, have more than one kidney tumor, or have a family history of kidney cancer, a referral to a genetics clinic may be offered so that inherited conditions can be looked for and family members can be tested if needed.
Clinical trials — New treatments for this cancer continue to be studied, and your oncologist can tell you whether a trial is open to you.

Questions to ask your doctor

What was the WHO/ISUP grade of my tumor, and what does that grade mean for me?
How large was my tumor, and what was the pathologic stage (pT and pN)?
Did my tumor contain sarcomatoid or rhabdoid cells, and if so, what percentage?
Was tumor necrosis seen under the microscope?
Did the tumor grow outside the kidney, into the fat, the renal sinus, or the renal vein?
Were the surgical margins negative or positive, and if positive, where?
Were any lymph nodes removed, and did any contain cancer?
Was lymphovascular invasion seen in my tumor?
What did the report say about the non-tumor kidney, and how well is my remaining kidney working?
What risk score was calculated for my tumor, and what is my chance of the cancer returning?
Based on my report, should treatment after surgery, such as pembrolizumab or pembrolizumab with belzutifan, be considered?
How often will I need imaging, and for how many years?
Should I be referred for genetic counseling or germline testing?
Is there a clinical trial that I should know about?