Spitz_Genodermatoses, 3e

Cowden Syndrome

Synonym(s) Inheritance

Multiple hamartoma syndrome; PTEN hamartoma tumor syndrome

AD; phosphatase and tensin homolog on chromosome 10 ( PTEN ) gene on 10q23

Prenatal Diagnosis

DNA analysis

Incidence

1:200,000-250,000; M:F = 1:2

Age at Presentation

Usually second to third decades of life; range from 4 to 75 years

Pathogenesis

PTEN hamartoma tumor syndrome includes Cowden syndrome and Bannayan-Riley- Ruvalcaba syndrome (BRRS); mutations in PTEN , a tumor suppressor gene that encodes a tyrosine phosphatase (PTEN), binds another PTEN; dimerized PTEN removes phosphate groups from proteins and fats to regulate the cell cycle; disruption signals activation and leads to cell proliferation in epidermis, gastrointestinal and oral mucosa, thyroid, and breast tissue Skin Facial tricholemmomas—tan-yellow verrucous papules Oral papillomas-”cobblestone” appearance on lips, gingival, labial, and buccal mucosa, oropharynx Acral keratotic papules—dorsal hands, wrists Palmoplantar translucent punctate keratoses Lipomas, angiomas (rare) Pigmented macules of glans penis (hallmark of BRRS) Breasts Fibrocystic disease, fibroadenomas, adenocarcinoma, gynecomastia (males) Thyroid Goiter, adenomas, thyroglossal duct cysts, follicular adenocarcinoma Gastrointestinal Hamartomatous polyps—throughout gastrointestinal tract but increased in the colon, usually benign Genitourinary Ovarian cysts, menstrual irregularities, endometrial carcinoma; tumors Vascular Arteriovenous malformations Craniofacial/skeletal Macrocephaly, adenoid facies, high-arched palate, kyphoscoliosis Neurodevelopmental Autism or developmental delay; cerebellar gangliocytoma “Lhermitte-Duclos”

Key Features

Differential Diagnosis

Lipoid proteinosis (p. 180) Muir-Torre syndrome (p. 200) Multiple endocrine neoplasia IIb (p. 212) Tuberous sclerosis (p. 92)

Laboratory Data

Molecular mutation testing Mammography Thyroid scan Thyroid function tests, CBC, urinalysis, stool guaiac, mammography, prophylactic bilateral mastectomy, pelvic examinations

Management

Referral to endocrinologist, gastroenterologist Referral to dermatologist—surgery, retinoids for cosmesis

Prognosis

If carcinoma detected early on, may have normal life span

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PTEN mutations are responsible for Cowden syndrome . . . There is overlap with BRRS, and cancer surveillance is appropriate for patients with both syndromes . . . Large head size helps support the diagnosis, and affected individuals often report difficulty fitting into standard-sized hats . . . Breast cancer has been reported in males as well . . . Laser vaporiza tion of trichilemmomas may be useful for cosmetic improvement . . . The most important intervention is excellent screening for malignancies according to guidelines provided by the NCCN . . . LE, JH

CLINICAL PEARLS

210