What is hereditary leiomyomatosis and renal cell cancer?
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary condition associated with multiple leiomyomas, which are smooth muscle tumors arising in the skin, uterine fibroids, which are non-cancerous growths in a woman’s uterus, and type 2 papillary renal (kidney) cancer. A person with HLRCC can have no skin tumors, a few, or many skin tumors. These skin tumors generally develop in adulthood and occur on the skin tumors, chest, back, arms, and legs; the tumors can be painful, but they are not cancerous. Women with HLRCC can develop uterine fibroids as young as their teens or early 20s.
What causes HLRCC?
HLRCC is a genetic condition. This means that the risk of cancer and other features of HLRCC can be passed from generation to generation in a family. A specific gene called the fumarate hydratase (FH) gene is believed to cause most cases of HLRCC. Research is ongoing to learn more about this condition.
How is HLRCC inherited?
Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. HLRCC follows an autosomal dominant inheritance pattern, in which a mutation (alteration) happens in only 1 copy of the gene. 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.
Having the mutation in 1 copy of the FH gene is enough to raise the risk of affected individuals to developing tumors. However, current research shows that a person with HLRCC must have mutations in both copies of the FH gene in order for kidney cancer to appear. In these cases, a person is generally born with 1 mutated gene (the autosomal dominant inheritance pattern described above; called a germline mutation) and then acquires a mutation to the second copy of the FH gene at some point during his or her lifetime in skin, uterus, or kidney cells (called a somatic alteration). Then, with both copies of the FH gene altered, the body loses its ability to suppress tumor growth.
Options exist for people interested in having a child when 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 which do not have the mutation. PGD has been in use for over 2 decades, and it 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 HLRCC?
HLRCC is considered to be rare. The number of people and families who have this condition is unknown.
How is HLRCC diagnosed?
HLRCC is suspected when a person has a history of multiple skin leiomyomas. A family history of fibroid tumors, particularly early in life, and type 2 papillary renal cancer, especially if it develops early, also raise the possibility of HLRCC. Genetic testing to look for mutations in the FH gene is available for people suspected of having HLRCC.
What are the estimated cancer risks associated with HLRCC?
HLRCC is associated with an increased risk of type 2 papillary renal cell carcinoma. For people with HLRCC, the estimated risk for this type of kidney cancer is about 15% to 30%.
What are the screening options for HLRCC?
There are no specific screening guidelines for HLRCC. The most common screening options for those with a germline FH gene mutation or those suspected to have HLRCC based on their signs or symptoms are regular skin examinations and an abdominal/pelvic computed tomography (CT) scan, which is a 3-dimensional picture of the inside of the body using an x-ray machine, with contrast, meaning a special dye, or a magnetic resonance imaging (MRI) every year. An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. If a suspicious kidney lesion is found, renal ultrasound examination, and/or an integrated positron emission tomography-computed tomography scan (PET-CT), which is a way to create pictures of organs and tissues inside the body using a small amount of a radioactive substance, may also be done to learn more about the suspicious area; however, these cannot replace a CT or MRI scan as screening tools. Also, women may be recommended to have regular gynecological examinations and imaging studies, such as an ultrasound, to look for uterine fibroids.
Screening options may change over time as new technologies are developed and more is learned about HLRCC. It is important to talk with your doctor 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 of 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?
If you are concerned about your family history and think your family may have HLRCC, consider asking the following questions:
Does my family history increase my risk of developing kidney cancer?
Are the skin changes or uterine tumors in me or my family considered leiomyomas?
Does my medical family history suggest the need for a cancer risk assessment?
Will you refer me to a genetic counselor or other genetics specialist?
Should I consider genetic testing?
Hereditary Leiomyomatosis and Renal Cell Cancer Family Alliance
National Cancer Institute
American Cancer Society
To find a genetic counselor in your area, ask your doctor or visit the following websites:
National Society of Genetic Counselors
National Cancer Institute: Cancer Genetics Services Directory