Kidney -

Clear cell renal cell carcinoma

This article was last reviewed and updated on August 26, 2019.
by Trevor A. Flood, MD FRCPC

Quick facts:

  • Clear cell renal cell carcinoma is a type of kidney cancer.

  • It is the most common type of kidney cancer in adults.

  • Your pathology report for clear cell renal cell carcinoma will include important information such as the tumour size and grade.

 

The normal kidney

The kidneys are two bean-shaped organs located near the back of your body just below the rib cage on both the left and the right side. The kidneys are composed of a complex network of millions of microscopic tubules.  These tubules act to filter your blood by removing waste products and toxins. The result of this filtration process is the production of urine. After the tubules in your kidneys produce urine, it travels through a thin tubular structure called the ureter. The ureter acts as a connection between the kidney and the urinary bladder. Urine is stored in the bladder before being excreted during urination.  

What is clear cell renal cell carcinoma?

Clear cell renal cell carcinoma is a type of kidney cancer. The tumour develops from the very small tubules in the kidney. Clear cell renal cell carcinoma is the most common type of malignant tumour to start in the kidney of adults.

 

How is this tumour normally found and diagnosed?

Many clear cell renal cell carcinomas are detected incidentally at the time of abdominal imaging for other reasons.  Patients with these tumours may occasionally experience pain in their back or side or notice blood in their urine. The tumour will appear as a kidney mass on MRI or CT scan of the abdomen.

 

Most cases of clear cell renal cell carcinoma are sporadic. That is they happen by chance and are unrelated to any known genetic condition. Some patients, however, are born with a syndrome, a genetic condition, that makes them more likely to develop clear cell renal cell carcinoma. Often these patients are at risk of developing multiple tumours and they arise at a younger age compared to patients with sporadic tumours.

The diagnosis of clear cell renal cell carcinoma can be made after a small sample of tissue is removed in a procedure called a biopsy biopsy. Depending on the results of the imaging studies, your doctor may suggest removing the tumour without first performing a biopsy.  

 

Patient with clear cell renal cell carcinoma are treated by removing part or all of the kidney in a procedure called a nephrectomy.

Tumour size

Tumour size is measured from the surgical specimen after it has been removed from the patient. These tumours are measured in three dimensions but usually only the greatest dimension is included in the report. The tumour size is usually reported in centimeters.

 

Why is this important? The tumour size is an important factor in determining the pathologic stage (see Pathologic stage below).

Number of tumours (focality)

Sometimes, more than one tumour is found in the same kidney. When only one tumour is found, pathologists call this unifocal. When more than one tumour is found, pathologists call this multifocal.

 

When multiple tumours are found, they are usually of the same type. For example, they are all clear cell renal cell carcinomas. However, different types of tumours can also be found in the same kidney. In that case, your report will list and describe each type of tumour found.

Sarcomatoid cells

The cancer cells in clear cell renal cell carcinoma are normally round in shape and they stick to each other to form groups of cancer cells throughout the tumour.

 

Sarcomatoid cells are cancer cells that have changed both their shape and their behavior. Cells that alter their usual appearance to look sarcomatoid can occur in essentially all types of renal cell carcinoma, including clear cell renal cell carcinoma. Instead of being round/oval in shape the cells are now elongated and spindled.

 

Why is this important? Tumours with sarcomatoid cells are considered high grade (see Grade below) and they are associated with worse prognosis.

Rhabdoid cells

Rhabdoid cells are cancer cells that have changed to look similar to muscle cells. Cells altering their appearance to look like rhabdoid cells can occur in essentially all subtypes of renal cell carcinoma, including clear cell renal cell carcinoma.

 

Why is this important? Like sarcomatoid cells, tumours with rhabdoid cells are considered high grade (see Grade below) and they are associated with worse prognosis.

Grade

Pathologists use the word grade to describe how different the cancer cells in clear cell renal cell carcinoma look compared the cells normally found in the kidney

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Pathologists divide the grade into two categories based on how the cancer cells look when examined under the microscope.
 

  • Low grade - The cells in this tumour are abnormal looking but are still similar to normal cells.

  • High grade - The cells in this tumour are very abnormal and do not look like normal cells.

 

Why is this important? Tumour made up of high grade cells behave in a more aggressive manner and are associated with worse prognosis.  

Fuhrman nuclear grade

A unique grading system is used for kidney cancers. It is called the Fuhrman nuclear grading system. This grading system can be applied to clear cell renal cell carcinomas and papillary renal cell carcinomas

 

The Fuhrman nuclear grade is based on microscopic features of the tumour cells including the size and shape of the nucleus as well as the prominence of the nucleoli.  The Fuhrman nuclear grading system divides kidney tumours into one of four grades: 

  • Grade 1 - The cancer cell nuclei are small and round.  The nucleoli are difficult to see even when the cells are examined with a high magnification lens.

  • Grade 2 – The cancer cell nuclei are slightly larger and irregularly shaped.  Nucleoli are easier to see but only after the cells are examined with a high magnification lens.

  • Grade 3 – The cancer cell nuclei are obviously irregular and enlarged.  The nucleoli are very easy to see even when the cells are examined with a low magnification lens.

  • Grade 4 - The cancer cell nuclei are bizarre, extremely irregular and often multilobed. Sarcomatoid and rhabdoid cells are included in this category. 

Why is this important? In general, high grade tumours (Fuhrman nuclear grades 3 and 4) have a worse prognosis than low grade tumours (Fuhrman nuclear grades 1 and 2).

Tumour necrosis

Necrosis is a form of cell death and it commonly occurs in cancers (malignant tumours). Your pathologist will closely examine the tumour for evidence of necrosis.

 

Why is this important? The presence of necrosis is important because it is associated with worse prognosis.

Tumour extension

The normal kidney sits near the back of the body and it is surrounded by fat. The adrenal gland sits directly above the kidney and the bladder is attached to the kidney by a long thin tube called the ureter which connects to the kidney in a region called the ‘renal sinus’.

 

Clear cell renal cell carcinoma starts inside the kidney but as it grows, it can extend into any of these structures and organs.

Your pathologist will carefully examine the specimen for any evidence of tumour extension and all structures or organs involved will be listed in your report.

 

Why is this important? Tumour extension into any of these structures or organs is important because it is associated with worse prognosis and it is also used to determine the pathologic stage (see Pathologic stage below).

Margins

A margin is the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery.

 

If only part of the kidney was removed (a procedure known as a ‘partial nephrectomy’), the margins will include the fat surrounding that portion of the kidney and the area where the kidney was divided.

 

If the entire kidney was removed (a procedure known as a ‘total’ or ‘radical nephrectomy’) the margins will include the fat surrounding the kidney, the ureter (the tube that connects the kidney to the bladder), and some large blood vessels (usually arteries and veins). Some larger specimens may include additional margins.

 

A margin is considered positive when the cancer cells are seen at the cut edge of the tissue. Your pathologist will report any positive margins and the location of that margin.

Why is this important? A positive margin is associated with an increased risk of the tumour coming back in the same area of the body.

Lymphovascular invasion

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.


Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.


Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion.


Why is this important? Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

Lymph nodes

Metastatic disease describes the process where cancer cells escape the main tumour and travel to another part of the body. Lymph nodes are small immune organs located throughout the body. They are a common target for metastatic disease.

 

Lymph nodes in the area of the tumour are often removed and submitted for pathological examination.

 

Most reports include the total number of lymph nodes examined and the number that contain cancer cells.

Why is this important? The presence of cancer cells in a lymph node (also called lymph node metastases) is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs.

Pathologic stage

​The pathologic stage for clear cell renal cell carcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer.

 

This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and worse prognosis.

 

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.


Tumour stage (pT) for clear cell renal cell carcinoma

Clear cell renal cell carcinoma is given a tumour stage between 1 and 4 based on the size of the tumour and the growth of the tumour into organs attached to the kidney.

 

  • T1 - The tumour is less than or equal to 7 centimeters and is still entirely within the kidney.

  • T2 - The tumour is greater than 7 centimeters but is still entirely within the kidney.

  • T3 - The tumour is grown into the fat around the kidney or into a large vein attached to the kidney.

  • T4 - The tumour has grown well outside the kidney and through a barrier known as ‘Gerota’s fascia’ OR into the adrenal gland above the kidney.

 

Nodal stage (pN) for clear cell renal cell carcinoma

Clear cell renal cell carcinoma is given a nodal stage of 0 or 1 based on the presence of cancer cells in a lymph node.

 

If no lymph nodes are involved the nodal stage is N0. If any cancer cells are seen in a lymph node the nodal stage is N1.

 

If no lymph nodes are submitted for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

Metastatic stage (pM) for clear cell renal cell carcinoma

Clear cell renal cell carcinoma is given a metastatic stage between 0 and 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

Pathologic findings in the non-neoplastic kidney

Non-neoplastic kidney is the tissue outside of the tumour. Your pathologist will carefully examine the non-neoplastic tissue for evidence of other diseases that can commonly affect the kidney such as arterionephrosclerosis (high blood pressure) and diabetic nephropathy (diabetes).

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