Cowden Disease
Definition
- Autosomal dominant multisystem disorder characterized by a variety of hamartomas and an increased incidence of carcinomas
Alternate/Historical Names
- Cowden syndrome
- Multiple hamartomas syndrome
- PTEN hamartomatous tumor syndrome (see below)
Diagnostic Criteria
- Autosomal dominant
- About half of cases appear to be de novo mutations
- See the National Comprehensive Cancer Network Genetics/High Risk Panel guidelines for application of the following findings to diagnosis
- Hamartomatous lesions in a variety of sites
- Mucocutaneous lesions are most commonly observed
- Facial trichilemmomas
- Palmar and plantar keratoses
- Acanthosis
- Dense orthokeratosis
- Prominent granular layer
- Facial papillomatous papules
- Mucosal fibromas
- Predominantly oral
- Dense fibrous core
- Variable Acanthosis and keratoses
- Sclerotic “plywood” fibromas
- Fascicles of hyalinized collagen separated by stromal mucin
- It is unclear how many of the facial papules and oral fibromas are of this type
- Breast hyalinized hamartomatous masses
- Intra- and extra-lobular sclerosis
- May become completely hyalinized
- Frequently multiple
- May be diffuse
- Gastrointestinal tract hamartomatous polyps
- Mucous retention cysts with prominent inflamed stroma
- Similar to juvenile polyps
- Frequently contain ganglion cells
- May resemble ganglioneuromas
- Central nervous system
- Adult Lhermitte-Duclos disease
- Neoplasms
- Breast carcinoma
- In situ and invasive
- Usually ductal
- Frequently involves sclerotic hamartomatous areas
- 25-50% lifetime risk
- Thyroid
- Carcinoma
- Follicular more frequent than papillary
- Approximately 10% lifetime risk
- Hyalinizing trabecular lesion (adenoma)
- Adenomatous goiter – very common
- Follicular adenomas – very common
- Uterus
- Endometrial carcinoma (probable)
- Risk probably 5-10%
- Leiomyomas
- Rarely observed
- Lipomas
- Renal cell carcinoma
- Melanoma
- Urothelial carcinoma
- Other
- Hashimoto thyroiditis
- Macrocephaly
- Mental retardation
- Genitourinary system malformations
- Esophageal glycogenic acanthosis
- PTEN Hamartomatous Tumor syndrome (PHTS) is the proposed name for a unified syndrome including Cowden Disease and Bannayan-Ruvalcaba-Riley syndrome (BRRS)
- BRRS is a pediatric disorder characterized by macrocephaly, developmental retardation and penile pigmented macules
- Among the many abnormalities, the following are of most relevance to surgical pathologists:
- Subcutaneous lipomas and angiolipomas
- Lymphangiomyomas and hemangiomas
- Angiokeratomas
- Pigmented macules of glans penis
- Intestinal hamartomatous polyps
- Hashimoto thyroiditis
- Increased GI cancer risk has not been demonstrated
- Both are associated with mutations of PTEN at 10q23.31
- Proteus syndrome and proteus-like syndrome are included by some in PHTS
- Congenital malformations, hemihytrophy, hamartomas, epidermal nevi, hyperostosis
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting and last update: 12/27/09, 11/12/11
