What is Cowden syndrome?

Cowden syndrome (CS) is part of the PTEN hamartoma tumor syndrome. Hamartomas are benign (noncancerous) tumor-like growths. Other conditions that are part of the PTEN hamartoma tumor syndrome are Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome.

CS is characterized by a high risk of both benign and cancerous tumors of the breast [2], thyroid [3], and endometrium [4] (uterus). Other key features of CS are skin changes (such as trichilemmomas [skin tags] and papillomatous papules) and macrocephaly (larger than average head size). The diagnostic criteria for CS are complex and reviewed by doctors frequently as new information becomes available. The current diagnostic criteria and features of CS are summarized below.

Classic features

• Adult Lhermitte-Duclos disease (in which a specific tumor type is found in the cerebellum of the brain)
• Skin changes (mainly around the face and mouth)
  • Trichilemmomas (skin tags)
  • Acral keratoses (thickened area of skin that may be red, yellow, or brown)
  • Papillomatous papules (small wart like growths)
  • Mucosal lesions

CS is diagnosed if any of the following are present: six or more facial papules, including at least three trichilemmomas; facial papules and oral papillomatous; or oral papillomatosis and acral keratoses; or six or more acral keratoses on the hands or feet.

Sometimes CS is difficult to diagnose, therefore doctors have devised categories to help arrive at a diagnosis. These categories are termed major and minor criteria.

Major features and diagnostic criteria

• Breast cancer
• Thyroid cancer (especially follicular)
• Macrocephaly (larger than average head size)
• Endometrial (uterine) cancer
• Lhermitte-Duclos disease

CS is diagnosed if a person has either Macrocephaly or Lhermitte-Duclos disease AND one other major feature.

Minor features and diagnostic criteria

• Benign thyroid changes (such as a goiter)
• Mental retardation
• Hamartomatous intestinal polyps (tumor-like growths)
• Fibrocystic changes in the breast
• Lipomas (benign fatty tumors)
• Fibromas (benign fibrous tumors)
• Genitourinary tumors (such as kidney cancer or uterine fibroids) or malformations

CS is diagnosed when a person has four or more of these minor features, or has one major feature and three minor features.

What causes CS?

CS is a genetic condition. This means that the risk of cancer and other features of CS can be passed from generation to generation in a family. Mutations (alterations) in the PTEN gene are known to cause CS.

How is CS inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. CS follows an autosomal dominant inheritance pattern in which a mutation happens in only one 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. It takes only one copy of the affected gene to have the disease. 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.

How common is CS?

CS is thought to be rare, although it is probably under-diagnosed. It is estimated that CS affects about one in every 200,000 individuals.

How is CS diagnosed?

CS is suspected when a person meets the clinical criteria for the diagnosis of CS, summarized above. Research is ongoing to better understand CS. Approximately 80% of the people who meet the current clinical diagnosis of CS will have a mutation in the PTEN gene. A blood test can determine if someone has a mutation in the PTEN gene. If a person has a mutation in the PTEN gene, he or she has CS.

What are the estimated cancer risks associated with CS?

• Breast cancer. The greatest cancer risk for a woman with CS is breast cancer. The lifetime risk for a woman with CS to develop breast cancer is estimated to be 25% to 50%. Breast cancer may develop earlier in women with CS than the general population. There appears to be some increased risk of breast cancer in men [5] with CS, but the specific risk is not known.
• Thyroid cancer. The risk of thyroid cancer in men and women with CS is estimated to be 10%. Thyroid cancer in CS is almost always the follicular type and only rarely the papillary type.
• Endometrial cancer. The estimated risk of endometrial cancer in women with CS is 5% to 10%.
• Other cancers. Many other types of cancer have been seen in people with CS. It is not yet known if the risk of these cancers is increased in people with CS. The list reported includes colon cancer, liver cancer, pancreatic cancer, ovarian cancer, bladder cancer, kidney cancer, melanoma, basal cell and squamous cell skin cancers, Merkel cell skin cancer, brain cancer, liposarcoma, and non-small cell lung cancer.

What are the screening options for CS?

It is important to discuss with your doctor the following screening options, as each individual is different:

General screening

• Yearly physical examination beginning at age 18, or five to 10 years younger than the earliest diagnosis of cancer in the family (whichever is sooner)
• Yearly examination by a dermatologist (a doctor who specializes in problems of the skin)
• Yearly urinalysis (examination of urine)
• Baseline colonoscopy at age 50
• Yearly ultrasound of the thyroid gland, beginning at age 18

Screening for women

• Monthly breast self-examination, beginning at age 18
• Yearly clinical breast examination (examination performed by a doctor or nurse), beginning at age 25, or five to 10 years younger than the earliest diagnosis of breast cancer in the family (whichever is sooner)
• Yearly mammogram and breast magnetic resonance imaging (MRI), beginning between the ages of 30 to 35, or five to 10 years younger than the earliest diagnosis of breast cancer in the family (whichever is sooner)
• Yearly endometrial biopsies, beginning between the ages of 35 to 40, or five to 10 years younger than the earliest diagnosis of endometrial cancer in the family (whichever is sooner)
• Yearly transvaginal ultrasound in post-menopausal women

Screening for men

• Monthly breast self-examination

Screening options may change over time as new technologies are developed and more is learned about CS. 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 [6].

Questions to ask the doctor

If you are concerned about your risk of cancer, talk with your doctor. Consider asking the following questions:

• What is my risk of developing 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 CS, consider asking the following questions:

• Does my family history increase my risk of cancer?
• Could my family have CS?
• Should I meet with a genetic counselor?

Additional resources

Guide to Breast Cancer [2]

The Genetics of Breast Cancer [7]

Guide to Thyroid Cancer [3]

The Genetics of Thyroid Cancer [8]

Guide to Uterine Cancer [4]

What to Expect When You Meet With a Genetic Counselor [9]

Facing Our Risk of Cancer Empowered (FORCE)
Information for women who are at a high risk of developing ovarian cancer or breast cancer.
www.facingourrisk.org [10]

National Cancer Institute
www.cancer.gov [11]

American Cancer Society
www.cancer.org [12]

CancerCare
www.cancercare.org [13]

To find a genetic counselor in your area, ask your doctor or visit these websites:

National Society of Genetic Counselors
www.nsgc.org [14]

National Cancer Institute: Cancer Genetics Services Directory
www.cancer.gov/cancertopics/genetics/directory [15]