Cowden syndrome

Overview

Part of PTEN-related diseases, caused by mutation of PTEN gene (AD inheritance with high but variable penetrance).

Also referred to as PTEN hamartoma tumour syndrome (PHTS) when grouped with related entities.

Key characteristics

Mucocutaneous lesions

Present in >90% and often the earliest manifestations (clinical hallmark).

• Trichilemmoma
• Mucocutaneous papillomatous papule
• Acral keratoses
• Glycogenic acanthosis
• Oral papillomas (tongue, gingiva)

Neurological

• Macrocephaly
• Intellectual disability

Lhermitte-Duclos disease (adult-onset dysplastic cerebellar gangliocytoma) is a major criterion

Harmatoma

• Thyroid
  • Adenoma
  • Multi-nodular goiters
• GI harmartomatous polyps (small and large bowel)
• Breast: benign breast disease (fibrocystic change, fibroadenomas)
• Uterine fibroid
• Lipoma
  • Testicular lipomatosis
• Fibromas

Malignancies

• Breast cancer: ~30-50%
• Thyroid cancer: ↑ risk of thyroid carcinoma (often follicular)
• Endometrial cancer: ~5-10%
• CNS: Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)