Chromophobe renal cell carcinoma

by Trevor A. Flood, MD FRCPC
March 7, 2023

What is chromophobe renal cell carcinoma?

Chromophobe renal cell carcinoma is a type of kidney cancer. The tumour develops from the very small tubules in the kidney. Chromophobe renal cell carcinoma is the third most common type of kidney cancer in adults. These tumours generally have an excellent prognosis except when sarcomatoid or rhabdoid cells are found.

What are the symptoms of chromophobe renal cell carcinoma?

Most patients with chromophobe renal cell carcinoma do not have any symptoms related to the tumour.

Can chromophobe renal cell carcinoma spread to other parts of the body?

Yes, the cells in this type of tumour can metastasize (spread) to other parts of the body including the lungs and liver. Compared to other types of kidney cancer, the risk of developing metastatic disease is much lower for chromophobe renal cell carcinoma.

What syndromes are associated with chromophobe renal cell carcinoma?

Most cases of chromophobe renal cell carcinoma are sporadic which means they occur 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 multiple chromophobe renal cell carcinomas and to develop them at a younger age.

One genetic syndrome that is associated with the development of chromophobe renal cell carcinoma is called Birt Hogg Dubé syndrome. Birt Hogg Dubé syndrome is characterized by the growth of multiple kidney tumours, including chromophobe renal cell carcinoma.  Other features of this syndrome include benign (non-cancerous) skin tumours and cysts in the liver.

How is this tumour normally found and diagnosed?

Many chromophobe renal cell carcinomas are found incidentally at the time of abdominal imaging for other reasons.  The tumour will appear as a kidney mass on an MRI or CT scan of the abdomen. The diagnosis of chromophobe 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.

What does chromophobe renal cell carcinoma look like under the microscope?

When examined under the microscope, the tumour cells in chromophobe renal cell carcinoma are polygonal in shape and the cells connect together to form large groups called sheets. The cells appear light pink to clear. Tumours with these kinds of cells are less likely to spread to other parts of the body and are associated with an excellent prognosis.

How do pathologists grade chromophobe renal cell carcinoma?

Pathologists divide chromophobe renal cell carcinoma into two grades – low and high – based on how much the tumour cells look like the cells normally found in the kidney. The grade can only be determined after the tumour has been examined under the microscope.

Chromophobe renal cell carcinomas tend to look and behave similarly.  They are associated with an excellent prognosis (except when sarcomatoid or rhabdoid cells are present or when they present at a high pathologic tumour stage; see sections below). For this reason, most tumours are considered low grade.

What are sarcomatoid cells and why are they important?

Sarcomatoid cells are tumour cells that have changed both their shape and their behaviour. Sarcomatoid tumour cells can be found in almost all types of renal cell carcinoma, including chromophobe renal cell carcinoma. Instead of being polygonal in shape, the sarcomatoid cells are now long and thin. Pathologists describe cells with this shape as spindle cells. Tumours with sarcomatoid cells are associated with a worse prognosis because they are more likely to spread to other parts of the body.

What are rhabdoid cells and why are they important?

Rhabdoid cells are tumour cells that have changed to look more like muscle cells. Rhabdoid tumour cells can be found in almost all types of renal cell carcinoma, including chromophobe renal cell carcinoma. Like sarcomatoid cells, tumours with rhabdoid cells are associated with a worse prognosis.

What does tumour necrosis mean?

Necrosis is a form of cell death and it commonly occurs in 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.

What does tumour extension mean and why is it important?

The normal kidney sits near the back of the body and 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’. Chromophobe renal cell carcinoma starts inside the kidney but as it grows, it can extend into any of these structures and organs. The growth of the tumour into surrounding organs is called tumour extension.

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).

What is a margin?

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

What does lymphovascular invasion mean?

Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. If lymphovascular invasion is seen, it will be included in your report.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. The cancer cells in chondroblastic osteosarcoma typically do not spread to lymph nodes and for this reason, lymph nodes are not always removed at the same time as the tumour. However, when lymph nodes are removed, they will be examined under a microscope and the results will be described in your report.

Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy”.

What pathologic stage is chromophobe renal cell carcinoma?

​The pathologic stage for chromophobe 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 a more advanced disease and a worse prognosis.

Tumour stage (pT) for chromophobe renal cell carcinoma

Chromophobe 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 chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma is given a nodal stage of 0 or 1 based on the presence of tumour cells in a lymph node. If no lymph nodes are involved the nodal stage is 0. If any tumour cells are seen in a lymph node the nodal stage is 1. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

Metastatic stage (pM) for chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma is given a metastatic stage of 0 or 1 based on the presence of tumour 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 sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.