Cowden disease (CD), also termed multiple hamartoma syndrome, is an autosomal dominant condition with variable expression that results from a mutation in the PTEN gene on chromosome arm 10q. Internationally, over 200 cases have been published. CD causes hamartomatous neoplasms of the skin and mucosa, GI tract, bones, central nervous system (CNS), eyes, and genitourinary tract. Skin is involved in 90-100% of cases; mucocutaneous features of CD include trichilemmomas, oral mucosal papilloma, acral keratoses, and palmoplantar keratoses.
Gastrointestinal (GI) abnormalities are present in as many as 72% of patients. Polyps can occur in the oesophagus, stomach, small or large intestine, or anus and are most common in the colon. These have been described as oesophageal squamous papilloma, hamartomatous and hyperplastic gastric polyps, adenoma, hamartoma and ganglioneuroma of colon. Although a few cases of adenocarcinoma of the colon in CD patients have been reported by Chen et al, the malignant potential of polyps is low.
The thyroid is involved in 66% of patients; manifestations include goitre, benign adenomas, and follicular adenocarcinomas. Thyroid cancer was diagnosed in 7% of patients (men more than women).
Carcinoma of the breast occurs in 20-36% of female patients and is one of the most serious consequences of CD. It also has been reported by Fackenthal et al in 2 men. Fibrocystic disease and fibroadenomas are present in approximately 75% of patients. Breast screening should be initiated early in women (possibly as soon as puberty is complete).
Lhermitte-Duclos disease currently is considered to be part of CD and is caused by hamartomatous growths of the cerebellum. Patients have macrocephaly, slowly progressive cerebellar ataxia (which usually appears in adulthood), and signs of increased intracranial pressure.
CD is associated with the development of several types of malignancy, which is why recognition of individuals with the syndrome is important. In particular, a marked increase is seen in the incidence of breast carcinoma in women and of thyroid carcinoma in both men and women. Reports also exist of several other types of malignancies occurring in patients with CD.
At least 40% of CD patients have a minimum of 1 malignant primary tumour, although with long-term follow-up care, this number may be higher. Yen et al have reported patients with more than 1 malignancy. Many of the cancers are curable if detected early. Close follow-up care of these patients is necessary.