What is Cowden syndrome?

Cowden syndrome (CS) is a hereditary disease of the skin and mucous membranes (known as genodermatosis). Because the disease is difficult to recognise, it is rarely diagnosed. Multiple hamartomas are typical of Cowden syndrome. These are tumour-like, benign tissue changes that develop due to defective germ tissue and increase the risk of developing malignant but also benign tumours. These can form mainly in the breast (mamma), in the thyroid gland, in the endometrium (endometrioma), in the kidneys, in the central nervous system or in the rectum of the colon. Cowden syndrome usually occurs in patients between the ages of 20 and 30, although both sexes can be equally affected. Doctors also distinguish a subtype of Cowden syndrome called Lhermitte-Duclos syndrome.

What causes Cowden's syndrome?

In about 60 to 80 per cent of all cases, a mutation in the hereditary disposition of the PTEN gene on chromosome 10 can be detected. Molecular genetic diagnostics that detect this mutation can therefore also help to diagnose Cowden syndrome. Because of this hereditary risk factor, the patient's first-degree family members should therefore also always be tested for the presence of this mutation.

What are the symptoms of Cowden syndrome?

Cowden syndrome is almost always manifested by multiple hamartomas, for example under the skin and mucous membranes. 99 percent of all patients also develop changes in the (mucous) skin that are characteristic of Cowden's syndrome, which can manifest themselves as follows:

• Trichilemmomas and papillomatous papules,
• oral and plantar keratoses
• multiple facial papules,
• macular pigmentation of the penis

Furthermore, hamartomatous or hyperplastic polyps may develop in the colon and/or stomach, sometimes also in the duodenum. Thyroid nodules, fibrocystic breast changes and lipomas and/or fibromas of the connective tissue are also not uncommon. If it is Lhermitte-Duclos syndrome, changes can also occur in the cerebellum. Doctors call this a cerebellar dysplastic gangliocytoma. In general, patients with Cowden syndrome often have a larger head circumference.

How is Cowden syndrome diagnosed?

Cowden syndrome is usually diagnosed genetically because of its complexity. However, in some cases, the diagnosis is extremely difficult. Medical professionals are therefore working on the development of diagnostic categories, which can be summarised as main and secondary criteria as follows:

• Main criteria:
• Breast cancer,
• Endometrioma carcinoma (tumour of the endometrium),
• follicular thyroid cancer,
• multiple gastrointestinal hamartomas, or ganglioneuromas (benign tumour of the nervous system),
• Macrocephaly (technical term for a large head),
• macular pigmentation of the glans (discoloured skin area on the glans),
• mucocutaneous lesions (hereditary vascular malformations),
• a biopsy-proven trichilemmoma,
• multiple palmoplantar keratosis (abnormal thickening of hands and feet),
• multifocal or extensive papillomatosis of the oral mucosa,
• Formation of multiple skin papules on the face, which may often have verrucous (wart-like) projections

• Secondary criteria:
• Colorectal cancer,
• Oesophageal glycogenic acanthosis (affecting the mucosa of the oesophagus),
• Autism spectrum disorder,
• mental retardation,
• papillary, or follicular variant of papillary thyroid cancer,
• structural lesions of the thyroid gland (for example, the formation of an adenoma, nodule or goitre),
• Renal cell carcinoma,
• Vascular abnormalities,
• Lipomas (benign soft tissue tumour),
• solitary gastrointestinal hamartoma, or ganglioneuroma (tumour-like, benign tissue change),
• Testicular lipomatosis

How is Cowden syndrome treated?

Cowden's syndrome can only be treated symptomatically. The disease should therefore be regularly examined with regard to its abnormalities for possible degeneration. If necessary, a tumour can be surgically removed or other therapeutic measures can be taken with regard to the symptom in question. Since Cowden syndrome also carries an increased risk for the development of benign or malignant tumours, patients should undergo cancer screening examinations. The following examinations are recommended at a certain point in time:

• from the time of diagnosis:
• an annual physical examination, especially of the skin;
• an annual thyroid check-up
• for female patients from the age of 18 onwards
• a monthly breast cancer screening by self-scanning of the mammary glands
• for female patients from the age of 25:
• an annual clinical breast examination performed by the attending gynaecologist
• for female patients from the age of 30 onwards
• an annual mammography and MRI examination of the breast
• an annual gynaecological screening examination, which includes a screening for uterine mucosal cancer
• from the age of 35 to 40 years onwards
• a colonoscopy at intervals of at least ten years,
• an ultrasound or MRI scan of the kidneys every two years

What is the prognosis for Cowden syndrome?

In 2010, a study on Cowden's syndrome was published. Based on 211 test persons, it was found that about 89 percent of all patients with CS develop at least one malignant tumour by the age of 70. The risk of being affected by a malignant tumour is reduced for male patients. The probability of developing colorectal cancer is about 15 percent and that of developing endometrial cancer is about 21 percent. Women who suffer from CS also have an increased risk of developing breast cancer.