Hereditary papillary renal carcinoma (HPRC)

Hereditary papillary renal carcinoma (HPRC) is a rare condition passed from parent to child that increases the risk of developing kidney cancer.

Kidney cancer is the development of abnormal growths in the kidneys—a pair of bean-shaped organs located in the back of your abdomen that work to filter water, salt and waste from your blood and create urine. These abnormal growths, or tumors, may grow out of control and spread to other parts of the body.

Papillary renal cell carcinoma is a subtype of renal cell carcinoma, which is the most common kidney cancer type. With this specific subtype, the cancer develops small finger-like projections within the tumor.

The link to cancer

The only symptom of hereditary papillary renal cell carcinoma is the development of cancerous tumors in the kidney. The renal cell carcinoma tumors that develop in HPRC patients usually are found in both kidneys and in multiple spots in the kidney.

This is an unusual presentation for these tumors. So if doctors discover these tumors, especially if you’re younger than 45, you’ll likely undergo a genetic test to determine whether you have hereditary papillary renal carcinoma.

HPRC isn’t linked to other cancers, unlike some other hereditary renal carcinoma syndromes. However, knowing whether you have the gene is important, because there’s the possibility that you may pass it along to your children or have family members who should be screened.

Causes and risk factors

HPRC is caused by a break in the genetic code of the body’s cells. The cells use this code to perform their daily actions and build their structures. But if some of the code breaks, it increases the chance that things may go awry, leading to uncontrolled cellular growth and, sometimes, to the development of cancer.

Specifically, hereditary papillary renal carcinoma is linked to breaks in a part of the genetic code called the MET gene. When functioning normally, the MET gene is a receptor on the outside of the kidney cells for hepatocyte growth factor.

Hepatocyte growth factor is a hormone produced by the body that encourages kidney cells to grow, usually during development in the womb or if there’s damage to kidney tissues. But when it’s broken, this receptor activates without the hormone, which leads to uncontrolled growth and cancer development.

These breaks in the MET gene are passed down in an autosomal dominant fashion, meaning you only need to inherit one broken copy of the gene to have the syndrome. All humans actually carry around two copies of their entire genetic code—one from each parent.

• If one parent has a broken MET gene, there’s a 50 percent chance he or she will pass it down to you, and because it’s dominant, you’ll have hereditary papillary renal carcinoma.
• If you have a broken MET gene and hereditary papillary renal carcinoma, there’s a 50 percent chance you’ll pass it down to each of your children, too.

The most common way to develop HPRC is to inherit it, though it’s also possible for the MET gene to break on its own—known as a de novo spontaneous mutation. There are no known risk factors that cause this break.

Symptoms of hereditary papillary renal carcinoma

The only symptom of hereditary papillary renal cell carcinoma is the development of kidney cancer, which usually happens just after turning 40 (though the age at which cancer develops varies widely by family, based on how the MET gene is broken).

So far, all reported HPRC patients have developed kidney cancer, according to the National Cancer Institute (NCI).

When the tumors are small, they don’t usually cause symptoms. If they grow larger, symptoms may include:

• Pain in the upper abdomen, back or sides
• Blood in the urine
• Lump in the abdomen or lower back

When HPRC kidney tumors become large, they may metastasize, most commonly to the lungs, and cause additional symptoms.

How hereditary papillary renal carcinoma is diagnosed

If you develop kidney tumors, your doctor may take a sample of the abnormal tissue (a biopsy) to examine under a microscope.

If you have hereditary papillary renal carcinoma, the doctors will see the tumor as well as noncancerous growths called adenomas in the outer layers of the kidney, plus those called papillary lesions inside the tubes of the kidney that filter the blood.

HPRC patients may develop up to 3,400 renal tumors or lesions per kidney, according to the NCI.

If you have lesions like those described above in your kidney tumor biopsy, your doctor will likely request a genetic test to determine whether you have hereditary papillary renal carcinoma.

If you know that direct relatives may have passed a broken MET gene along, you’ll want to get tested early to see if you have it.

Treatment for hereditary papillary renal carcinoma

Patients who have tested positive for mutations linked to hereditary papillary renal carcinoma will typically get regular computed tomography (CT) or magnetic resonance imaging (MRI) scans of their kidneys to monitor for the development of tumors.

If these screenings find tumors developing in the kidneys, doctors may not take a biopsy or remove them. Instead, they may wait and monitor the tumors.

Tumors that grow to be bigger than 3 cm wide, or about the size of a grape, need to be surgically removed, which is done by excising part of the kidney. Your care team will try to keep as much of the kidney as possible.

If the cancer spreads to other areas of your body, doctors may discuss chemotherapy and radiation options. Treatment with drugs that block the activity of the MET receptor are currently being tested in clinical trials.