Cowden syndrome

Cowden syndrome, also known as multiple hamartoma syndrome, is characterised by multiple hamartomas throughout the body and increased risk of several cancers.

Terminology

Type 2 segmental Cowden syndrome is the association of Cowden syndrome with a Cowden naevus when it is considered a type of epidermal naevus syndrome.

Clinical presentation

The disease is characterised by ⁷:

• mucocutaneous lesions: present in >90% of cases

  • trichilemmomas

  • mucocutaneous papillomatous papules

  • acral (palmoplantar) keratoses

• macrocephaly

• intellectual disability

• thyroid abnormalities

  • thyroid adenomas

  • multinodular goitre

• gastrointestinal hamartomatous polyps (small and large bowel)

• fibrocystic disease of the breast and fibroadenoma

• uterine leiomyoma

• lipomas, including testicular lipomatosis ⁶

• fibromas

• glycogenic acanthosis

In addition to benign tumour formation, Cowden syndrome carries a recognised increased risk of multiple malignancies ^1,7:

• breast cancer: develops in 30-50% of those with the syndrome 

• thyroid cancer: develops in 5% of those with the syndrome, usually follicular

• endometrial cancer: develops in 5-10% of those with the syndrome

• CNS: dysplastic cerebellar gangliocytoma, occurs when in association with Lhermitte-Duclos disease

• possible increased risk of renal cell carcinoma, colorectal carcinoma, and melanoma

Pathology

Genetics

It carries an autosomal dominant inheritance with variable (but high) penetrance ⁷. A gene locus for the disease has been identified on chromosome 10q22-23, a mutation of the PTEN gene ⁷.

Thus, Cowden syndrome is part of a group of disease known as PTEN-related diseases, which also includes ^3,7:

• Lhermitte-Duclos disease

• Bannayan-Riley-Ruvalcaba syndrome (BRRS)

History and etymology

First described in 1963 by K M Lloyd and M Dennis with the surname of their first patient: Cowden ².