Cowden disease

What is Cowden disease?

Cowden disease is a rare inherited condition characterised by hamartomas in various tissues. Cowden disease is also known as ‘Cowden syndrome’ and ‘multiple hamartoma syndrome’.

Cutaneous features

Benign hamartomas of the skin and mucosa are present in nearly all cases.

• Facial papules — flesh-coloured flat-topped dry or warty 1 to 5-mm fibrous papules and trichilemmomas around the mouth, nostrils and eyes.
• Oral lesions — numerous 1–3 mm smooth whitish spots on the gums and palate that join together to create a cobblestone appearance known as papillomatosis.
• Acral keratoses — flesh-coloured or slightly pigmented smooth or warty papules on the upper surface of hands and feet (in more than 60% of patients).
• Palmoplantar keratoses — scaly spots on the palms and soles (in about 40% of patients).

Other skin lesions occurring less frequently include lipomas, neuromas and haemangiomas.

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

Facial papule

Acral keratoses

Close-up

Non-cutaneous features

• Abnormalities of the thyroid are present in about 60% of patients. These are usually harmless growths but occasionally may be cancerous.
• Breast tumours are the most important non-cutaneous association. Fibrocystic disease resulting in benign lumps in the breasts is present in about 75% of women. Breast cancer occurs in 20–36% of patients.
• Gastrointestinal polyps and other abnormalities are present in about 72% of patients.
• Genitourinary tract involvement may include ovarian cysts and cancers.
• Central nervous system — Lhermitte-Duclos disease is caused by a hamartoma of the cerebellum (rare).
• Skeletal abnormalities such as bone cysts.

What is the cause of Cowden disease?

Cowden disease is due to an abnormal PTEN tumour suppressor gene on chromosome 10q23. The PTEN protein product controls cell growth by promoting normal cell death. A mutation on the PTEN gene leads to loss of the protein's function and results in overproliferation of cells that form hamartomatous growths.

Cowden syndrome is an autosomal dominant condition meaning half of an affected person's children also have the syndrome.

How is Cowden disease diagnosed?

A diagnosis of Cowden disease can be made using the criteria below.

Hamartomas confined to the skin and mucous membrane meet the criteria if:

• Six or more facial papules are present, of which 3 or more must be trichilemmomas,
• Facial papules and oral mucosal papillomatosis are present,
• Oral mucosal papillomatosis and acral keratoses are present, or
• Six or more palmoplantar keratoses are present.

The diagnosis of Cowden disease may also be made when there are:

• Two major criteria, where one is macrocephaly or Lhermitte-Duclos disease,
• One major and 3 minor criteria, or,
• Four minor criteria.

Diagnosis in a family in which one individual is diagnostic for Cowden disease is made when:

• Any single major criterion with or without minor criteria is met.
• Two minor criteria are met.

What is the treatment for Cowden disease?

Patients with Cowden disease need to undergo medical and physical examinations and appropriate laboratory and radiographic tests on a yearly basis to check for internal malignancies. Genetic counselling of relatives is very important especially females who are at most risk for malignant complications.

Treatment of the cutaneous features includes:

• Oral retinoids, usually acitretin, which may temporarily control some of the cutaneous lesions. Lesions often reappear when treatment is stopped.
• Surgical care of facial papules using chemical peels, laser resurfacing, surgery and/or shave excisions.

At least 40% of patients with Cowden disease have at least one cancer. If cancers are detected early their cure rate is high with appropriate treatment. Patients need to be followed-up regularly by a multidisciplinary team of doctors.