Clear cell renal cell carcinoma

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 kidney cancer in adults.

The kidneys

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 sides. 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.

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.

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. Depending on the results of the imaging studies, your doctor may suggest removing the tumour without first performing a biopsy.

When examined under the microscope, the tumour is made up of large round cells that connect together to form large groups of cells. The tumour gets its name from the fact that many of the tumour cells appear clear when examined under the microscope. Tumours with these kinds of cells are less likely to spread to other parts of the body and are associated with an excellent prognosis. The groups of tumour cells are often separated by small blood vessels that provide the tumour with a large amount of blood.

Syndromes associated with clear cell renal cell carcinoma

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.

What to look for in your report after the tumour is removed

Tumour size

This is the size of the tumour measured in centimetres. These tumours are measured in three dimensions but usually, only the greatest dimension is included in the report. The tumour size is an important factor in determining the pathologic stage (see Pathologic stage below).

Number of tumours

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

Sarcomatoid cells are cancer cells that have changed both their shape and their behaviour. Sarcomatoid cancer cells can be found in almost all types of renal cell carcinoma, including clear cell renal cell carcinoma. Instead of being round or oval in shape, the sarcomatoid cells are now long and thin. Pathologists describe cells with this shape as spindle cells. Tumours with sarcomatoid cells are considered high grade (see WHO/ISUP grade below) and they are associated with a worse prognosis.

Rhabdoid cells

Rhabdoid cells are cancer cells that have changed to look similar to muscle cells. Rhabdoid cancer cells can be found in almost all types of renal cell carcinoma, including clear cell renal cell carcinoma. Like sarcomatoid cells, tumours with rhabdoid cells are considered high grade (see WHO/ISUP grade below) and they are associated with worse prognosis.

WHO/ISUP grade

Pathologists use the word grade to describe how different the cancer cells in clear cell renal cell carcinoma look compared to the cells normally found in the kidney. Pathologists use a unique grading system called the WHO/ISUP for both clear cell renal cell carcinoma and another similar tumour called papillary renal cell carcinoma. Prior to 2016, these tumour types were graded using Fuhrman nuclear grading system.

The WHO/ISUP grading system and the Fuhrman nuclear grading system are similar and both employ a scoring system from 1 to 4. The WHO/ISUP grade is based on microscopic features of the tumour cells, in particular, the size and shape of the cancer cell nuclei and the presence of nucleoli.

The WHO/ISUP 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. Tumours with sarcomatoid and rhabdoid cells are included in this category.

In general, high-grade tumours (WHO/ISUP nuclear grades 3 and 4) have a worse prognosis than low-grade tumours (WHO/ISUP nuclear grades 1 and 2) and are more likely to spread to other parts of the body.

Tumour necrosis

Necrosis is a form of cell death and it commonly occurs in malignant (cancerous) tumours. Your pathologist will closely examine the tumour for evidence of necrosis. The presence of necrosis is important because it is associated with a 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. Tumour extension into any of these structures or organs is important because it is associated with a 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.

Margin

 

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 negative margin means that no cancer cells were seen at the cut edge of the tissue. In contrast, a positive margin means that cancer cells are seen at the cut edge of the tissue. Your pathologist will report any positive margins and the location of that margin. 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.

lymphovascular invasion

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. 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

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

Lymph node

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

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 a worse prognosis.

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 centimetres and is still entirely within the kidney.
  • T2 – The tumour is greater than 7 centimetres 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 of 0 or 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

The 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).

by Trevor A. Flood, MD FRCPC (updated July 28, 2021)
A+ A A-