From the Guidelines
Cowden syndrome is a rare genetic disorder that significantly increases the risk of certain cancers, including breast, thyroid, endometrial, and colorectal cancer, and management involves regular cancer surveillance and genetic counseling, as recommended by the National Comprehensive Cancer Network 1.
Key Features of Cowden Syndrome
- Caused by mutations in the PTEN gene, which normally helps regulate cell growth and division
- Characterized by multiple benign growths called hamartomas and an increased risk of certain cancers
- People with Cowden syndrome typically develop skin abnormalities like trichilemmomas, papillomatous papules, and acral keratoses
- The condition significantly increases the risk of breast cancer (up to 85% lifetime risk in women), thyroid cancer, endometrial cancer, and colorectal cancer
Management and Surveillance
- Regular cancer surveillance including:
- Annual mammograms and breast MRIs starting at age 30
- Thyroid ultrasounds starting at age 18
- Colonoscopies starting at age 35
- Endometrial screenings starting at age 30-35
- Genetic counseling is recommended for affected individuals and their families, as the condition follows an autosomal dominant inheritance pattern
- Diagnosis is based on clinical criteria and can be confirmed through genetic testing for PTEN mutations
Importance of Early Detection and Surveillance
- Early detection of cancers through surveillance is crucial for improved outcomes
- Regular surveillance and screening can help identify cancers at an early stage, when they are more treatable
- Genetic counseling and testing can help identify individuals at risk of developing Cowden syndrome and allow for early intervention and surveillance
Recommendations for Individuals with Cowden Syndrome
- Annual comprehensive physical examinations starting at 18 years of age, or 5 years before the youngest age of cancer diagnosis in the family 1
- Breast awareness and clinical breast examination every 6-12 months starting at age 25
- Consideration of risk-reducing surgeries, such as mastectomy, on a case-by-case basis
- Patient education regarding the symptoms of endometrial cancer and the importance of prompt response to these symptoms
- Annual random endometrial biopsies and/or ultrasound starting around 30-35 years of age
- Annual thyroid ultrasound starting at age 18 or 5-10 years before the earliest known thyroid cancer diagnosis in the family
- Colonoscopy starting at age 35, performed every 5-10 years, or more frequently in patients who are symptomatic or in whom polyps are found
- Renal ultrasound starting at age 40 and then every 1-2 years thereafter
- Psychomotor assessment in children at diagnosis, and brain MRI only in the presence of localizing neurologic signs or symptoms
- Education regarding the signs and symptoms of cancer, and genetic counseling for at-risk relatives
From the Research
Definition and Characteristics of Cowden Syndrome
- Cowden syndrome (CS) is a rare inherited condition characterized by multiple hamartomas in various tissues from all three embryonic layers 2.
- It is a cancer predisposition syndrome with an increased risk of developing malignancy in many tissues, especially breast, thyroid, and endometrium 2, 3.
- CS is inherited in an autosomal dominant manner, with approximately 80% of patients having a germ-line mutation of the PTEN tumor suppressor gene 2.
Clinical Features and Diagnosis
- Presenting signs and symptoms of CS are highly non-specific, making it essential for clinicians to recognize the syndrome for early cancer screening and genetic testing 2.
- The clinical symptoms of CS do not always correlate with genetic results, emphasizing the importance of diagnosing the disease using both clinical and genetic approaches 4.
- Cardinal features of CS include hamartomas, macrocephaly, and increased risk of breast, thyroid, renal, uterine, and other cancers, as well as benign neoplasias and neurodevelopmental concerns 3.
Genetics and Management
- Germline PTEN mutations are associated with CS, as well as other syndromes, including Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome, which can be described under the umbrella of PTEN hamartoma tumor syndrome (PHTS) 5.
- Management guidelines for cancer screening and risk reduction in patients with CS continue to be updated, with separate clinical diagnostic criteria and PTEN testing guidelines created to assist clinicians in diagnosis 6.
- Appropriate surveillance procedures are crucial to detect any further tumors in patients with CS, and recent improvements in genetic testing highlight the importance of diagnosing this disease using both clinical and genetic approaches 4.