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Cowden’s syndrome

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Benign and malignant hamartoma type lesions in skin and mucocutaneous tissues, thyroid and breast tissue, and associated with a higher risk of male breast cancer.

Autosomal dominant clinical disorders associated with mutations of the PTEN or phosphatase and tensin homolog gene on chromosome 10.

Cowden syndrome is the most common phenotype of PTEN mutations, with an estimated incidence of 1 in 200,000-250,000 people.

Clinical characteristics include macrocephaly, mucocutaneous lesions such as trichlemmomas, papillomatous papules, acral keratosis, and an increased risk for benign and malignant tumors.

A rare, hereditary cancer syndrome characterized by germline PTEN mutation and development of malignant and benign tumors in various organs.

Associated with small flesh colored 1-4 mm papules found mainly on the head and neck.

Skin lesions may appear wart-like.

Papules may involve the tongue and gingiva and produce a cobblestone appearance on those structures.

Wart-like papules on the dorsum of the feet and hands may be present.

Keratoses on the soles, palms and sides of the feet may be present.

Patients may have lipomas and hemangiomas.

Fibrocystic disease of the breast seen in almost all patients, and 25-50% ultimately develop breast cancer, which may be bilateral.

62% of patients have thyroid tumors and 10% of those are malignant.

5-10% of patients develop endometrial cancer.

Hamartomatous gastrointestinal polyps occur in about one third of patients.

Linked to mutations of PTEN/MMAC1 tumor suppressor gene on chromosome 10q22-23 encoding a tyrosine phosphatase protein that regulates cell proliferation.

Patients inherit 1 mutant inactive copy of PTEN from either parent, and the loss of the second allele results in tumor formation.

Human HPV DNA has been found in trichilemmomas, flesh colored papules.

Is a marker for the development of breast cancer and thyroid cancer.

Estimated lifetime risk for cancer: 85% for breast cancer, 35% for thyroid cancer, 34% for kidney cancer, 28% for endometrial cancer, and 9% colon cancer.

Vigorous screening for breast cancer is recommended, and it should begin at age 30 years as the malignancy appears 5-10 years sooner than the earliest known familial breast cancers.

Annual thyroid ultrasound of the thyroid should be done beginning at age 18 years.

For premenopausal women annual endometrial biopsy is suggested and for postmenopausal women annual endometrial ultrasound is advised.

A trial of sirolimus is associated with some of evidence of improvement in symptoms, skin and G.I. lesions, cerebellar function and decreased mTOR signaling.

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