What is PTEN (Phosphatase and Tensin Homolog) hamartoma syndrome?

From the Guidelines

Patients with PTEN hamartoma syndrome should undergo regular cancer surveillance with enhanced screening protocols starting at younger ages than the general population, including breast cancer screening at age 25, thyroid ultrasounds at diagnosis, and colonoscopies at age 35, as this approach has been shown to improve outcomes in this high-risk population 1.

Overview of PTEN Hamartoma Syndrome

PTEN hamartoma syndrome is a rare genetic disorder caused by mutations in the PTEN gene, which normally functions as a tumor suppressor. This syndrome encompasses several related conditions, including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and PTEN-related Proteus syndrome. Patients with this condition develop multiple benign growths called hamartomas throughout the body, particularly in the skin, gastrointestinal tract, and other organs.

Cancer Risks and Surveillance

The syndrome significantly increases the risk of developing certain cancers, especially breast, thyroid, endometrial, colorectal, and kidney cancers. According to recent studies, the lifetime risk of developing breast cancer in patients with PTEN hamartoma syndrome is between 67 and 85% 1. Therefore, early and regular surveillance is crucial for detecting these cancers at an early stage when they are more treatable.

Management and Treatment

Management involves regular cancer surveillance with enhanced screening protocols starting at younger ages than the general population. For example, women should begin breast cancer screening at age 25, thyroid ultrasounds should start at diagnosis, and colonoscopies should begin at age 35 1. Genetic counseling is essential for affected individuals and their families. Treatment focuses on addressing specific symptoms and early cancer detection rather than treating the underlying genetic mutation.

Inheritance Pattern

The condition is inherited in an autosomal dominant pattern, meaning each child of an affected person has a 50% chance of inheriting the mutation. Early diagnosis and vigilant monitoring are crucial for improving outcomes in patients with PTEN hamartoma syndrome.

Key Recommendations

• Regular cancer surveillance with enhanced screening protocols starting at younger ages than the general population
• Breast cancer screening at age 25
• Thyroid ultrasounds at diagnosis
• Colonoscopies at age 35
• Genetic counseling for affected individuals and their families
• Treatment focusing on addressing specific symptoms and early cancer detection rather than treating the underlying genetic mutation

These recommendations are based on the most recent and highest-quality studies, including those published in the British Journal of Cancer 1 and Clinical Cancer Research 1.

From the Research

Overview of PTEN Hamartoma Syndrome

• PTEN hamartoma tumor syndrome (PHTS) is a genetic disorder characterized by an increased risk of developing cancer and benign tumors, particularly in the breast, thyroid, endometrium, colon, and kidney 2, 3, 4.
• The syndrome is caused by pathogenic germline variants in the PTEN gene, which is a tumor suppressor gene 2, 3.

Clinical Features and Cancer Risks

• Patients with PHTS are at increased risk of developing various types of cancer, including breast, thyroid, endometrial, renal, colorectal, and melanoma 2, 3, 4.
• The median age at diagnosis of cancer in PHTS patients is 36 years, with cumulative lifetime cancer risks (CLTRs) ranging from 81% to 90% 2.
• Specific cancer risks include:
  • Breast cancer: 67% to 85% CLTR by age 60-70 2
  • Thyroid cancer: 6% to 38% CLTR 2
  • Endometrial cancer: 19% to 28% CLTR 2
  • Renal cancer: 2% to 24% CLTR 2
  • Colorectal cancer: 9% to 32% CLTR 2
  • Melanoma: 0% to 6% CLTR 2

Surveillance and Management

• Regular surveillance is recommended for PHTS patients to detect cancer at an early stage, including:
  • Breast cancer screening starting at age 25-30 4
  • Thyroid cancer screening starting at age 10-18 5, 4
  • Renal cancer screening starting at age 25-30 4
  • Colorectal cancer screening starting at age 25-30 4
• A multidisciplinary approach is necessary for the management of PHTS patients, involving clinicians from various specialties, including genetics, gynecology, endocrinology, dermatology, radiology, gastroenterology, and general surgery 3, 4.

Red Flags for Early Recognition

• Certain phenotypic characteristics can serve as red flags for early recognition of PHTS in adults, including:
  • Macrocephaly
  • Multinodular goiter (MNG)
  • Oral features such as gingival hypertrophy, high palate, and oral papillomas 6
• Scoring two out of three of these characteristics can yield a sensitivity of 100% for recognizing PHTS in adults 6.