Hereditary Papillary Renal Carcinoma

Approved by the Cancer.Net Editorial Board , 01/2020

What is hereditary papillary renal carcinoma?

Hereditary papillary renal carcinoma (HPRC) is a hereditary condition that increases the risk of papillary type of renal cell carcinoma ( kidney cancer ). Tumors in HPRC are a specific type of papillary cancer called type 1 papillary renal cell cancer. Individuals with HPRC have an increased risk of multiple kidney tumors in one or both kidneys (also called bilateral kidney tumors). Currently, no other types of cancer or noncancerous health problems are known to be related to HPRC.

What causes HPRC?

HPRC is a genetic condition. This means that the risk for type 1 papillary renal cell cancer can be passed from generation to generation in a family. Mutations (alteration) in a gene called MET are linked to HPRC development. MET is a gene that encodes for a tyrosine kinase receptor  that binds to an important growth factor known as hepatocyte growth factor (HGF). Research is ongoing to learn more about HPRC.

How is HPRC inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. HPRC follows an autosomal dominant inheritance pattern, in which inheriting 1 copy of the altered gene is sufficient to put the individual at risk for developing cancer. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person's test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk.

Options exist for people interested in having a child a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos that do not have the mutation. PGD has been in use for over 2 decades, and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is HPRC?

HPRC is considered to be rare. The number of people and families who have HPRC is unknown. However, there are approximately 30 families in published medical reports.

How is HPRC diagnosed?

HPRC is suspected when multiple family members have type 1 papillary renal cell cancer or an individual has bilateral, multifocal type 1 papillary renal cell cancer. Genetic testing to look for mutations in the MET gene is available for people suspected of having HPRC. Germline genetic testing can be for a single gene or a larger panel of genes.

What are the estimated cancer risks associated with HPRC?

The specific risk for type 1 papillary renal cell cancer in families with HPRC is extremely high, with some estimates showing the lifetime risk is nearly 100%. If kidney cancer is diagnosed, talk with your doctor about treatment options. Currently, surgery is the primary method of treating a localized tumor in people with HPRC when a tumor reaches greater than 3 cm in size. A drug called foretinib has shown evidence of being effective in a small study of patients with localized or metastatic HPRC but is not currently approved by the U.S. Food and Drug Administration. Other drugs in this area are also being studied in clinical trials for non-hereditary (or sporadic) papillary kidney cancer.

What are the screening options for HPRC?

There are no specific screening guidelines for families suspected of having HPRC. Individuals in these families are encouraged to talk with their doctor about screening options for kidney cancer, including:

  • Computed tomography (CT or CAT) scan. A CT scan takes pictures of the inside of the body using x-rays taken from different angles. A computer combines these pictures into a detailed, 3-dimensional image that shows any abnormalities or tumors. A CT scan can be used to measure the tumor’s size. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a pill or liquid to swallow.

  • Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. MRI can be used to measure the tumor’s size. A special dye called a contrast medium is given before the scan to create a clearer picture. This dye can be injected into a patient’s vein or given as a pill or liquid to swallow.

  • Ultrasound. An ultrasound uses sound waves to create a picture of the internal organs. However, an ultrasound may miss small lesions and is not a recommended screening strategy. As HPRC tumors may not have brisk enhancement, leading to confusion of cystic vs solid composition, an ultrasound  may be useful as an additional test to confirm a lesion is solid.

Screening guidelines may change over time as new technologies are developed and more is learned about HPRC. It is important to talk with your health care team about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans .

Questions to ask the health care team

If you are concerned about your risk for kidney cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing kidney cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening and prevention?

If you are concerned about your family history and think your family may have HPRC, consider asking the following questions:

  • Does my family history increase my risk of developing kidney cancer?

  • Should I meet with a genetic counselor?

  • Should I consider genetic testing ?