Kidney cancer is sort of a strange cancer. It is not well understood by many doctors (even some general oncologists). I was a stomach doctor for 30 years and knew little about it. What I knew was that if you get it — and it spreads — you die. Fortunately medical research has changed my view.

The body is made up of many different kinds of cells. During our development in the uterus of our mother different cells get together and form the different organs of the body. The kidneys are a pair of organs of the body. The kidneys are part of the urinary tract. They make urine by removing waste from the blood that flows through the kidney tubules. They also help control the amount of water and salt in our body. Urine collects in a space (renal pelvis) in the middle of each kidney. It passes from the renal pelvis into the bladder through a tube called a ureter. When you “pee” the urine leaves the body through another tube (the urethra) which is in the penis in a male and the urethral opening in the vagina in a female.

Part of the problem with finding kidney cancer early is that the kidneys (we have two, which is a good thing) actually sit along the back on either side of the spine in the lower abdominal cavity. They are about the size of a fist. They are separate from the other organs in the abdomen as they are behind what is called the retroperitoneum — a layer of tissue that forms a covering around the abdominal organs. Therefore a kidney mass can become large before it causes any trouble and a test is done to see what is wrong. On top of each kidney is the adrenal gland. Thus there is a right and a left kidney. Around each kidney and adrenal gland is a mass of fatty tissue and an outer layer of fibrous tissue called Gerota’s fascia.

The organs of the body need new cells to replace the old ones that die. This cell growth is a carefully controlled process. This is under control of the genes which sit in the center or nucleus of the cell. We inherit genes from our mother and father. The genes are made of deoxyribonucleic acids (DNA). DNA is like a vast information database that tells the cells when and how to grow. The DNA has a complete set of instructions for making all the parts a cell will ever need.

This whole process can sometimes not work as it should. DNA is made of a string of chemical bases called nucleotides. The four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T).The order of the nucleotides acts like a code that is read by the cell. For normal cell processes to work the order of the nucleotides is very important. There can be changes in the order of the nucleotides in the gene (a gene mutation) that can cause things to go very wrong. The nucleotides code for amino acids, which in turn form proteins. In certain cases these mutations can alter the protein function. In some cases, these altered proteins (“oncoproteins”) can induce cells to grow when they should not, or do not die and get replaced when they should. This abnormal growth of tissue is called a tumor. A tumor can be benign or malignant.

A benign tumor will not spread and if removed usually will not grow back. A malignant tumor is more aggressive. At times it can grow back if removed and may spread (metastasize) to other areas of the body. This kind of tumor is called a cancer. It can be life threatening.

How you learn that you have kidney cancer really depends on where in the world you live. If is in a country with a well funded and modern medical system it is often found “incidentally” on an x-ray) often an ultrasound, CT scan or MRI) that was done for another reason. If you are from a country that does not have easy access to scanning machines the kidney cancer may be found because of problems it is causing. This may be from the kidney mass (tumor) itself, and manifest as blood in the urine, pain in the flank, or the development of mass or bump which can be felt in the flank area. The problems may be from spread (metastasis) of the kidney cancer to other organs (areas) of the body). In general the more advanced the cancer is the more problems it can cause.

The kind of kidney cancer that you may have depends on which cells of the kidney became abnormal or cancerous.

Clear cell renal cell cancer
The most common kind of kidney cancer is called clear cell renal cell carcinoma. This accounts for about 80% of kidney cancer. It is more common in men than women. It usually occurs from age 45-60. This comes from the cells that line the kidney tubule-the part of the kidney that makes the urine. When looked at under a microscope the cells look clear and pale. This type of kidney cancer is usually due to a mutation in the von Hippel Lindau (VHL) gene. There are families with inherited mutations of VHL, who develop kidney cancers in addition to other medical problems. The large majority of people who develop clear cell renal cell carcinoma have a non-inherited or “sporadic” version. Because of the medical research that has found this gene abnormality there has been a great advance in the treatment of this type of kidney cancer. I am still alive because of this research and the new medications that have been developed.

Papillary renal cell carcinoma
The second most common type is called papillary renal cell carcinoma. This accounts for about 15% of kidney cancer.. The name is from little finger-like projections (called papillae) in some, if not most, of the tumors. There are 2 main types of papillary kidney cancer. Type 1 is generally less aggressive. There is a small subset of people who can inherit this type of papillary renal cell carcinoma. Type 2 tends to be more aggressive, and in rare cases is part of a hereditary syndrome as well. This type of papillary kidney cancer is more serious and harder to treat.

Oncocytoma
This accounts for about 5 % of renal tumors. This usually is a solitary tumor that is benign. However a form of oncocytic cancer an occur.

Chromophobe RCC
This accounts for about 5% of RCC. Overall this is usually less aggressive than clear cell. However there are times it can be more serious and can spread.

Collecting duct renal cell carcinoma
This subtype is very rare. The major feature is that the cancer cells can form irregular tubes. This tumor type is very aggressive, and has traditionally been treated with chemotherapy.

Genetic translocation cancer of the kidney
This is a distinct form of kidney cancer that can occur in young adults (including females) and probably children. It may make up approximately one-third of pediatric RCC. This can be diagnosed by special staining (immunohistochemical staining) of tissue from the kidney tumor. There are genetic abnormalities called translocations in the TFE3 gene (Xp11.2 translocation). Approximately 10% to 15% of translocation RCCs occur in children that had prior cyto-toxic chemotherapy for a prior cancer. Therefore translocation RCCs should be added to the list of chemotherapy-associated secondary neoplasms in children (along with acute leukemias, soft tissue sarcomas, and malignant gliomas).

Renal Medullary Cancer
This rare yet aggressive cancer can be found in young adults that have have sickle cell trait or rarely sickle cell disease. In those with sickle cell trait the person carries one normal copy of the hemoglobin A gene (HbA) and one copy of the hemoglobin A gene harboring the genetic mutation found in sickle cell disease (HbS). These individuals do not have sickle cell disease but can develop kidney disease. These people may show visible (gross) hematuria, abdominal or back/flank pain, abdominal mass, enlarged lymph nodes and significant weight loss.

Pediatric Renal Tumors

In children below age 15, renal cell carcinoma is quite rare. In this age group the most common renal cancer is Wilms disease, The next most common types of kidney tumor in children are:, Clear cell renal cell carcinoma, Clear cell sarcoma and Rhabdoid tumors. Clear cell sarcoma is more likely than Wilms tumor to metastasize (spread) to the lungs, brain or bones. It is also more likely than Wilms tumor to come back after treatment.

Wilms’ Tumor or nephroblastoma

Wilms tumor can run in families from genes passed down from their parents. Most tumors are found in children around 3 years of age. Older children are less likely to get Wilms tumor. Above age 6, these tumors are rare.
People of African descent have the highest rates of Wilms’ tumor. Females are also more likely than males to develop the tumors. About 500 cases per year are diagnosed in the US. Wilms tumor occurs in otherwise healthy children. In 10% of cases occur in children with other developmental abnormalities. These include hemi-hypertrophy (abnormal growth on 1 side of the body) cryptorchidism (the absence of one or both testes from the scrotum), and hypospadias (a birth defect of the urethra in the male where the urinary meatus (opening) is abnormally placed. Symptoms can include abdominal mass, abdominal pain, blood in the urine, and fever of unknown cause. Body imaging (ultrasound and/or CT) is vital for diagnosis.

Staging is determined by body imaging (US and/or CT) and pathology. There are 5 stages depending on tumor size, tumor extension beyond the kidney, lymph node spread, distant metastases, and if it involves one or both kidneys. Stage 1-3 accounts for 90% of patients.

Prognosis depends on stage and pathology. Therefore the staging always should include the stage and pathology. There are 2 prognostic groups based on the pathology of the tumor. Favorable has the classic 3 tissue components: the triphasic nephroblastoma. Based on the look of the Wilms tumor cells, doctors may put the tumor into one of two subtypes:

• If the nuclei of the cells look normal it has a favorable histology. About 95% of Wilms tumors fit into this subtype, which means they are easier to cure.
• If the nuclei of the cells look much larger than normal and do not have a normal shape this is a unfavorable histology. Any stage that contains anaplastic pathology carries a worse prognosis than the same stage with favorable pathology.

It is a very treatable tumor with 90% of patients surviving more than 5 years. It must be stressed that the treatment approach is vital to achieving a good response. A multi-disciplinary team consisting of pediatric specialists (pediatric surgeon/urologist,pediatric oncologist, pediatric radiation oncologist) that have extensive experience treating children with cancer is needed. Most patients should be offered a clinical trial to obtain the most advanced treatment. In the US at a children’s oncology center Wilms tumor with the favorable histology subtype has a 90% to 98% survival rate. Wilms tumor with the unfavorable histology subtype has a survival rate between 60% and 80%

Pediatric Renal Cell Cancer

This is a rare diseases in children. Renal cell carcinoma is more common than Wilms’ tumor after the age of 10 years. However, it is far less common overall than Wilms’ tumor. Conventional clear cell renal cell carcinomas make up about 15% of kidney cancers in children. While in young adolescents age 15-19 renal cell carcinoma can account for 2/3rds of kidney malignancies .They can present with similar findings as an adults. In this age group papillary renal cancer is more common than in adults. There is a unique type of renal cancer (genetic translocation cancer of the kidney) that can be found in young adults and probably children as well.

Inherited Disorders
There are a several inherited disorders that include kidney cancer as part of other abnormalities.

Birt-Hobbe Dube Syndrome
This is an inherited syndrome. where people can get multiple chromophobe and/or oncocytic kidney cancer. Renal oncocytoma (benign) can also occur. People can get benign tumors of the hair follicle ,a rupture of a bleb-a bulge in the lung tissue-that can cause a spontaneous pneumothorax (air in the pleural cavity of the chest between the lung and the chest wall) and colon polyps.

Von Hippel-Lindau Syndrome
As noted above, VHL is a rare disease that runs in some families. It is caused by changes in the VHL gene which increases the risk of kidney cancer. It also can cause cysts or tumors hemangioblastoma) in the eyes, brain, and other parts of the body (including a tumor of the adrenal gland called pheochromcytoma.). There can also be light brown spots on the skin called “cafe au lait” spots There is genetic testing (via a blood test) for this abnormal gene. This is the same gene that can become abnormal in someone’s kidney after they are born and can cause clear cell kidney cancer to occur sporadically.

Tuberous Sclerosis
Tuberous sclerosis or tuberous sclerosis complex (TSC) is a rare inherited genetic disorder that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lung and skin. It is caused by mutations in genes that control cell growth and differentiation ( the kind of cell that develops).About 50% of people with TSC have learning difficulties with some showing signs of autism. 60-80% have kidney tumors called angiomyolipoma that frequently cause blood in the urine, they can also have benign cysts of the kidney and rarely renal cell carcinoma. Skin abnormalities will be present in 96% of people with TSC. Most cause no problems but are helpful in diagnosis.