Genetic Disorder Reference Sheet: PTEN Hamartoma Tumor Syndrome

March 21, 2023 by Suzanne M. Mahon DNS, RN, AOCN®, AGN-BC, FAAN

Alterations in the phosphatase and tensin (PTEN) homologue gene result in PTEN hamartoma tumor syndrome (https://doi.org/10.1038/s41431-020-0651-7), which includes Cowden, Bannayan-Riley-Ruvalcaba, and PTEN-related Proteus and Proteus-like syndromes. Pathogenic variants in the PTEN gene are associated with increased risk for developing multiple benign and malignant tumors, some of which may occur in childhood.

Cancer Risks

A person with a pathogenic PTEN variant has an estimated 85%–89% overall risk (https://doi.org/10.1038/s41431-020-0651-7) of developing malignancy and most will have some manifestations by age 20–29 (https://doi.org/10.1111/cge.13875). Pathogenic variants are associated with the following tumor risks (https://www.ncbi.nlm.nih.gov/books/NBK1488/).

Tumor Type

Incidence

Average Age of Onset

Female breast cancer

25%–80%, penetrance is 50% by age 50

38–50 years

Benign thyroid nodules

30%–68%

38 years

Thyroid cancer (usually follicular, occasionally papillary)

13%–35%

38 years

Uterine fibroids

Common

35–45 years

Endometrial cancer

20%–30%

35–45 years

Renal cancer

15%–35%

40–49 years

Gastrointestinal polyps, including ganglioneuromas, hamartomas, juvenile, and adenomas

13%–16%

30–39 years

Melanoma

6%

As young as 5 years

Testing, Identification, and Early Detection

Prompt identification of people with pathogenic PTEN variants allows providers to implement a complex and aggressive screening and prevention program to decrease their risk for morbidity and mortality. If tumor testing identifies a pathogenic PTEN variant, refer the patient for germline testing. Individuals with a known germline pathogenic PTEN variant in the family should also be referred for counseling and testing. 

Clinical presentation of germline PTEN pathogenic variants varies, but guidelines for referral for evaluation (https://nccn.org/) are based on combinations of criteria (https://doi.org/10.3390/cancers11060844).

Genetic Disorder Reference Sheet: PTEN Hamartoma Tumor Syndrome

Note: See visual examples of trichilemmomas (https://www.ncbi.nlm.nih.gov/books/NBK1488/figure/phts.F1/) and papillomas (https://www.ncbi.nlm.nih.gov/books/NBK1488/figure/phts.F2/).

The Cleveland Clinic’s PTEN Risk Calculator (https://www.lerner.ccf.org/gmi/ccscore/) is an evidence-based clinical scoring system that providers can use to identify adults for referrals or consideration for research studies. It creates a mathematical model for each patient’s individual factors; those with a threshold probability of 3% or higher should be referred for testing. The tool has a projected sensitivity of 90% for detection of patients with a PTEN pathogenic variant.  

Screening and Risk Reduction

People with a pathogenic PTEN variant should follow established management recommendations (https://nccn.org/) that involve rigorous screening (https://www.ncbi.nlm.nih.gov/books/NBK1488/) and consider risk-reducing surgery.

Screening

Surgery

Other Prevention Strategies

Implications for Nurses

Germline testing and management of individuals with a pathogenic PTEN variant requires ongoing lifetime screening, both of which begin at age 5 (https://www.ncbi.nlm.nih.gov/books/NBK1488/). Families need psychosocial support and a consistent team of providers to implement prevention and detection measures.


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