COWDEN SYNDROME (MULTIPLE HAMARTOMA SYNDROME)
COWDEN SYNDROME (MULTIPLE HAMARTOMA SYNDROME) ICD-10: Q85.9
• Cowden syndrome (named after the propositus) is a rare, autosomal-dominant heritable cancer syndrome with variable expressivity in a number of systems in the form of multiple hamartomatous neoplasms of ectodermal, mesodermal, and endodermal origin.
• Germ-line mutations in the tumor-suppressor gene PTEN are located on chromosome 10q22–23 in most cases.
• There is a special susceptibility for breast and thyroid cancers, and the skin lesions are important markers.
• Skin lesions may appear first in childhood and develop over time. They consist of trichilemmomas, skin-colored, pink (Fig. 19-11A), or brown papules and have the appearance of flat warts on the central area of the face, lips, and the ears; translucent punctate keratoses of the palms and soles; and hyperkeratotic, flat-topped papules on the dorsa of the hands and forearms. Mucous membranes: papules of the gingival, labial (Fig. 19-11B), and palatal surfaces that coalesce, giving a “cobblestone” appearance. Papillomas of the buccal mucosa and the tongue.
• In addition to breast cancer (20%), which is often bilateral, and thyroid cancer (8%), there are various internal hamartomas:
• Breast: Fibrocystic disease, fibroadenomas, adenocarcinoma, and gynecomastia in males.
• Thyroid: Goiter, adenomas, thyroglossal duct cysts, and follicular adenocarcinoma.
• GI tract: Hamartomatous polyps throughout tract but increased in large bowel; adenocarcinoma arising in polyp.
• Female genital tract: Ovarian cysts and menstrual abnormalities.
• Musculoskeletal: Craniomegaly, kyphoscoliosis, “adenoid” facies, and higharched palate.
• CNS: Mental retardation, seizures, neuromas, ganglioneuromas, and meningiomas of the ear canal.
• It is important to establish the diagnosis of Cowden syndrome so that these patients can be followed carefully to detect breast and thyroid cancers early.
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B
FIGURE 19-11 • Cowden syndrome (A) Multiple skin-colored warty papules on the face, which represent trichilemmomas. (B) Multiple reddish, confluent papules on the oral mucosa giving a cobblestone appearance.