This page was reviewed under our medical and editorial policy by
Maurie Markman, MD, President, Medicine & Science
This page was updated on March 2, 2022.
Hereditary renal oncocytoma syndromes are a set of genetic diseases that may cause growths in the kidneys. These growths, called renal oncocytomas, generally aren’t cancerous. However, the hereditary syndromes that increase your chances of developing oncocytomas often also increase the risk of developing other kidney growths and kidney cancer in the form of renal cell carcinoma (RCC).
The kidneys are a pair of bean-shaped organs located in the back of the abdomen that filter water, salt and waste from your blood to create urine. Oncocytomas are a rare type of kidney tumor that may develop in the cells lining the kidney’s tubes, or nephrons.
It’s rare for them to spread from the kidney to other areas of the body, but they can get quite large and cause symptoms of their own.
Oncocytomas generally are associated with a couple of hereditary syndromes. Hereditary syndromes are passed down from parent to child through genetic material or caused by breaks in the genetic code.
This genetic code gives our cells the instructions they need to make proteins that serve as the structures of our bodies and as the machines that perform the cells’ actions. When a mutation “breaks” the instructions that the cells need to grow normally, they may grow out of control and lead to cancer or tumors.
When oncocytomas are caused by one of these syndromes, they usually appear earlier in life and show up in multiple places in both kidneys.
Birt-Hogg-Dubé syndrome (BHD): This syndrome involves a suite of symptoms linked to a break in a gene called FLCN. The FLCN gene makes a protein called folliculin. Researchers aren’t sure what this protein does normally, but it may act as a check on cell growth to stop tumors from forming. When the folliculin gene is broken, growths develop in the skin and kidneys.
Symptoms of Birt-Hogg-Dubé syndrome include:
Not everyone with Birt-Hogg-Dubé syndrome shows all of these symptoms. They may show up in varying degrees depending on the patient. They usually appear in young adulthood in the face and neck area.
Many BHD patients may develop oncocytomas, and it’s estimated that 15 percent to 30 percent of BHD patients develop kidney cancer, according to the American Society of Clinical Oncology.
Tuberous sclerosis complex (TSC): This set of syndromes is characterized by developmental problems, skin changes and the development of noncancerous tumors in many parts of the body. The affected organs frequently include the heart, brain and kidneys. Estimates vary, but tuberous sclerosis complex is thought to affect about one in 6,000 people, according to the U.S. National Library of Medicine (NLM).
Symptoms of tuberous sclerosis complex can be serious, even life-threatening. They include:
Tuberous sclerosis complex is caused by mutations in the TSC1 or TSC2 gene. These two genes work together to control cell growth and size. If they’re broken, cells can grow out of control and cause tumors.
Most TSC patients develop a variety of kidney growths. The most common growth in 75 percent to 80 percent of TSC patients is angiomyolipoma, a benign fatty growth in the kidney, according to a review in Advances in Chronic Kidney Disease. Cysts and oncocytomas may also develop. Fewer than 5 percent of TSC patients develop kidney cancer, according to the same review.
There are no known environmental causes of the genetic breaks that may lead to hereditary renal oncocytomas. They’re either random developments or passed directly from parent to offspring.
Both Birt-Hogg-Dubé syndrome and tuberous sclerosis complex mutations are passed down in an autosomal dominant manner. This means that everyone who has the broken gene has the syndrome and shows at least some symptoms of it—and each child of those affected has a 50 percent chance of being affected as well.
Mutations of the TSC1 and TSC2 genes are also passed down in the same way, but this accounts for only a third of TSC mutations, according to the NLM. The rest of these breaks develop spontaneously in the body during conception and aren’t inherited from either parent. It’s unknown what may cause these newly broken genes.
While some symptoms of tuberous sclerosis complex, including increased risk of developing growths, show up with only one broken gene, the actual development of growths requires two broken copies of TSC1 or TSC2. One of the broken genes is inherited or develops spontaneously during conception, while the second copy can break due to a breakdown in natural repair mechanisms in the cell.
When both copies of the gene are broken in an organ, the cell starts growing out of control and becomes an abnormal growth or tumor.
Symptoms of hereditary renal oncocytoma tend to crop up in about a third of patients, usually when a tumor becomes large. These symptoms include:
Renal oncocytomas are usually found by chance during imaging tests for other conditions. To receive a confirmed diagnosis of oncocytoma (vs. renal cell carcinomas or other tumors), doctors need to take a tissue sample from the tumor and study it under a microscope.
Once your care team has confirmed that the growths are oncocytomas, they may order a genetic test to determine whether these were caused by one of the hereditary syndromes mentioned above. This is a test in which a blood sample is examined in a laboratory to check for a broken FLCN, TSC1 or TSC2 gene.
For tuberous sclerosis complex specifically, the symptoms usually start near birth, with the development of tumors in the heart. Patients may then start to show developmental delays and skin changes, and develop new growths throughout childhood and adolescence. Doctors may put together these signs and request genetic testing of the TSC1 and TSC2 genes.
Oncocytomas are generally removed surgically, especially when they get large and start causing symptoms. Another reason for surgery is that these growths may be difficult to differentiate from other types of kidney growths, including cancers.
If your care team determines the growths are noncancerous, they may try to save as much of the kidneys as they can while removing the tumor. These tumors don’t usually regrow after they’re removed, and they don’t affect the lifespan of the patient directly.
However, if the syndrome causing the oncocytomas also causes cancer, the patient may require more aggressive treatments, including chemotherapy and radiation therapy.
For tuberous sclerosis complex syndrome, more extensive treatments and interventions are needed to deal with the host of symptoms that develop in individual patients throughout different parts of their lives.
Medications may help slow tumor growth, though surgery may be needed for some. Medications used to treat the symptoms of tuberous sclerosis complex syndrome, specifically seizures and tumors, include Afinitor® (everolimus) and Sabril® (vigabatrin).
Patients with Birt-Hogg-Dubé syndrome may have skin growths removed and may need additional treatment (including surgery) if lung issues develop.