What is Cowden syndrome (CS)?

From the Guidelines

Cowden syndrome patients should undergo regular cancer surveillance, including annual mammograms and breast MRIs beginning at age 30, annual thyroid ultrasounds starting at diagnosis, colonoscopy every 5 years beginning at age 35, and endometrial screening for women, to reduce the risk of breast, thyroid, endometrial, and colorectal cancers. This is based on the high lifetime risks of these cancers in patients with Cowden syndrome, which are estimated to be 81% for female breast cancer, 21% for thyroid cancer, 19% for endometrial cancer, and 15% for renal cancer 1. The management of Cowden syndrome should focus on primary and secondary prevention options for these cancers, as well as education regarding the signs and symptoms of cancer and genetic counseling for at-risk relatives 1.

Key Recommendations

• Annual comprehensive physical examinations beginning at 18 years of age, or 5 years before the youngest age of cancer diagnosis in the family
• Breast awareness beginning at 18 years of age, clinical breast examination every 6 to 12 months beginning at age 25 years, and annual mammography and breast MRI screening beginning at age 30 to 35 years
• Annual thyroid ultrasound beginning at age 18 years or 5 to 10 years before the earliest known thyroid cancer diagnosis in the family
• Colonoscopy starting at age 35 years, performed every 5 to 10 years, or more frequently in patients who are symptomatic or in whom polyps are found
• Renal ultrasound starting at age 40 years and then every 1 to 2 years thereafter

Cancer Risks

• Breast cancer: 81% lifetime risk 1
• Thyroid cancer: 21% lifetime risk 1
• Endometrial cancer: 19% lifetime risk 1
• Renal cancer: 15% lifetime risk 1
• Colorectal cancer: 9% lifetime risk 1

Genetic Counseling

• Cowden syndrome follows an autosomal dominant inheritance pattern, meaning each child of an affected person has a 50% chance of inheriting the condition
• Genetic counseling is essential for patients and family members to discuss the risks and benefits of genetic testing and risk-reducing surgeries 1

From the Research

Definition and Characteristics of Cowden Syndrome

• Cowden syndrome is a rare cancer predisposition syndrome inherited in an autosomal-dominant fashion 2, 3
• It is characterized by hamartomatous polyps that affect multiple organs, including skin, mucous membranes, thyroid, breast, gastrointestinal tract, endometrium, and brain 2, 4
• The syndrome is associated with an increased risk of developing malignancy in many tissues, especially breast, thyroid, and endometrium 2, 4, 5, 3, 6

Diagnosis and Clinical Features

• The diagnosis of Cowden syndrome can be made clinically when patients present with a combination of symptoms such as mucocutaneous lesions with a strong personal or family history of thyroid, breast, endometrial, and colorectal cancer 6
• A high index of suspicion is required to provide a clinical diagnosis utilizing major and minor criteria 6
• The diagnosis can be confirmed by genetic testing for a PTEN mutation, a tumor suppressor gene 3, 6

Management and Surveillance

• Early and accurate diagnosis of Cowden syndrome is essential because it is a cancer predisposition syndrome that carries an increased risk for developing malignancy in many tissues, especially breast and thyroid 2
• Patients with Cowden syndrome require regular screening to allow for early detection of disease 4, 5, 6
• Cancer surveillance should be performed for those with positive genetic testing as well as those with negative genetic testing who still meet clinical diagnostic criteria 6
• Guidelines for cancer screening, including surveillance and management plans, should be distinguished from those of the general population 2