PTEN Hamartoma Tumor Syndrome

What is PTEN hamartoma tumor syndrome (PHTS)?

PTEN hamartoma tumor syndrome (PHTS) refers to a group of syndromes that involve a mutation, or change, in your PTEN gene. PTEN is a tumor suppressor gene. It makes an enzyme that prevents uncontrolled cell growth that causes tumors. Cells can grow out of control when there’s a mutation, causing hamartomas.

A hamartoma (pronounced “HA-mar-TOH-muh”) is a benign, or noncancerous, tumor-like growth. If you have PHTS, you’re at increased risk of developing hamartomas and other benign growths. You may also be at increased risk of developing malignant (cancerous) tumors.

What syndromes are considered PHTS?

PHTS includes Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome (BRRS). Doctors once viewed Cowden syndrome and BRRS as separate conditions. Now, they’re classified under the larger PHTS umbrella because they’re both associated with mutations in your PTEN gene.

People with PHTS and BRRS face similar health risks. People with PHTS can develop characteristics associated with both Cowden syndrome and BRRS over their lifetimes.

• Cowden syndrome: Adults most commonly develop Cowden syndrome. People with this condition may develop both benign (noncancerous) and malignant (cancerous) tumors. These tumors most commonly affect your breasts, uterus, thyroid, gastrointestinal tract, skin, tongue and gums.
• Bannayan-Riley-Ruvalcaba syndrome (BRRS): BRRS most commonly affects children. Children with BRRS may develop tumors on their skin and birthmarks. They may also experience developmental delays.

What are the signs and symptoms of PHTS syndrome?

PHTS causes hamartomas to form throughout various tissues in your body. Specific signs and symptoms vary depending on which syndrome associated with PHTS you have. If you have PHTS, you may develop any of the following:

Skin growths

• Skin tags (acrochordons).
• Dark flat spots on your hands and feet (palmoplantar keratoses).
• Small, smooth growths that form on your face (trichilemmomas).
• Skin-colored raised bumps (papillomas).
• Fatty tumors underneath your skin (lipomas).
• Hard lumps inside of your mouth (oral fibromas).
• Blood vessel growths that appear through your skin (hemangiomas and birthmarks).
• Freckling on your penis.

Benign tumors

• Thyroid nodules.
• Multinodular goiters.
• Uterine fibroids.
• Fibroadenomas of the breast.
• Fibrocystic breasts.
• Polyps in your upper gastrointestinal tract and colon (colon polyps).

Brain and developmental issues

• Large head size (macrocephaly).
• An especially long head shape (dolichocephaly).
• Developmental delays.
• Autism spectrum disorder.

What causes PHTS?

PTEN hamartoma tumor syndrome (PHTS) results from a mutated, or changed, PTEN gene. PTEN releases an enzyme that tells cells to stop dividing. This enzyme also tells a cell when it’s time to die (apoptosis) to make space for new, healthy cells.

With PHTS, the PTEN gene doesn’t work correctly. As a result, cells may keep dividing and grow out of control. They may eventually form tumors. These tumors are usually benign, but they can become cancerous.

PHTS is an inherited genetic condition, which means children can inherit the mutated gene from their biological parents.

How is PHTS inherited?

You inherit PHTS in an autosomal dominant pattern. Everyone has two copies of the PTEN gene. You inherit one copy from each parent. With PHTS, you inherit one working copy of the PTEN gene and one with the mutation. Although you have one working copy, the mutated PTEN gene causes problems associated with PHTS.

In some instances, you don’t inherit a mutated PTEN gene. Instead, you develop a new mutation before you’re born, while still an embryo or fetus.

Regardless of how you got the mutation, once you have it, you have a 50% chance of passing the copy of the mutated gene onto your child.

What are the cancer risks associated with PHTS?

If you have Cowden syndrome, you’re at greater risk than the general population for certain cancers. You’ll need lifelong cancer screening to manage the risk. Screening can’t prevent cancer, but early detection can lead to early treatment and better outcomes.

You may be at greater risk of:

• Breast cancer.
• Thyroid cancer.
• Kidney cancer.
• Uterine cancer.
• Colorectal cancer.
• Melanoma.

More research is needed to understand the cancer risks of BRRS.

How is PHTS diagnosed?

Your healthcare provider will diagnose you with PHTS if they find a mutation in the PTEN gene. You’ll need to receive genetic testing to see if you have a mutation, which will involve a blood test.

The National Comprehensive Cancer Network and Cleveland Clinic have established genetic testing guidelines for Cowden syndrome that are updated frequently based on new research. Additionally, the International Cowden Consortium has developed criteria for diagnosing Cowden syndrome. Your healthcare provider will consider factors like your symptoms to determine whether you should get tested. They’ll consider whether you have a family member with a history of tumors or PTEN mutations.

There aren’t standard guidelines for diagnosing BRRS, but your healthcare provider may recommend tests for diagnosing Cowden syndrome.

If you have the mutation, your family members should also receive testing.

Is there a cure for PHTS?

There isn’t a cure for PHTS. Currently, scientists are researching treatments that may work best on cancers that involve a PTEN mutation.

How is PHTS syndrome treated and managed?

Your care team may include multiple healthcare providers who can help address your symptoms and issues, ranging from abnormal growths to developmental delays. They’ll assess your cancer risk to determine how often you should receive cancer screenings.

Treatments

There aren’t specific guidelines for treating benign or malignant tumors with a PTEN mutation. Instead, treatment will address your symptoms. Treatments may include:

• Surgery: Excising (cutting out) abnormal tissue. Your healthcare provider may remove a tissue sample and test the cells for signs of cancer (biopsy) before deciding to proceed with surgery.
• Cryotherapy: Using extreme cold to destroy abnormal tissue.
• Laser ablation: Using extreme heat to destroy abnormal tissue.
• Medicated topical creams: Using creams with ingredients designed to destroy skin growths.

Cancer screening

If you have Cowden syndrome, you’ll need lifelong surveillance to monitor for benign and cancerous growths to detect any issues at the earliest, most treatable time. Although there aren’t standard guidelines for monitoring people with BRRS, your healthcare provider may recommend similar screening as with Cowden syndrome.

Screening procedures may include frequent:

• Mammograms: An imaging procedure that uses low-dose X-rays to produce pictures of your breast tissue.
• Breast MRIs: An imaging procedure that uses a large magnet and radio waves to produce pictures of your breast tissue.
• Ultrasounds: An imaging procedure that uses sound waves to produce pictures of your breast tissue.
• Colonoscopies: A test that uses a scope to produce images of the inside of your colon. The scope also can remove polyps, which can stop pre-cancerous growths from becoming cancer.
• Endoscopies: A test that uses a scope to produce images of your esophagus, stomach and duodenum (the upper part of your small intestine).

Depending on the results, you may need a biopsy to determine if abnormal tissue contains cancer cells.

How can I prevent PHTS?

There’s no way to prevent PHTS, but regular cancer screenings can help catch cancer early, when it’s most treatable. Follow your healthcare provider’s guidance on whether and how often you should be screened.

What can I expect if I have PHTS?

Your outlook depends on many factors, including your symptoms and overall health. You’re at increased risk of developing certain types of cancer if you have PHTS/Cowden syndrome. This is why cancer screenings are so important. Catching and treating cancer early is one of the best ways to improve your prognosis.

When should I see my healthcare provider?

Follow your healthcare provider’s guidance on how often you should get cancer screenings. It’s also important to know the potential warning signs of cancer. Ask your healthcare provider about any symptoms that you should be on the lookout for.

How does PTEN cause cancer?

A PTEN mutation can cause cells to grow out of control and form tumors. While PHTS is most commonly associated with benign tumors called hamartomas, out-of-control cell growth can also cause malignant tumors to form. Both tumor types occur when cells multiply rapidly. Unlike benign growths that stay in one place, cancerous tumors can spread throughout your body (metastasize). The cancer cells damage healthy tissue as they spread.

What conditions are closely associated with PTEN hamartoma tumor syndrome (PHTS)?

Having PHTS increases your risk of developing several cancers, especially cancers that affect your breast, thyroid and gastrointestinal (GI) tract. Many people with PHTS have a larger-than-average head size (macrocephaly), skin growths and various benign tumor types.

A note from Cleveland Clinic

Learning of a PHTS diagnosis can be difficult, whether the diagnosis applies to you or your child. It’s a condition that requires close monitoring — news that most people find frustrating. Still, careful screening can potentially save or prolong your life if you develop cancer. Ask your healthcare provider about your health risks if you’re diagnosed with PHTS. Ask about your care team’s approach to monitoring your health, including how your care plan can potentially improve your long-term health.