Cowden's Disease

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Contents 1 Introduction 2 Epidemiology 3 Pathology 4 Genetics 5 Clinical-manifestations 6 Laboratory 7 Radiology 8 Complications 9 Differential-diagnosis 10 Management 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

Introduction

• Rare hereditary neoplastic syndrome

• Lhermitte-Duclos disease ( dysplastic cerebellar gangliocytoma & related symptoms) is seen in a subset of Cowden's disease.

Epidemiology

• fewer than 100 cases reported
• age of onset 4-75 years, median age 40 years
• males > females
• mostly in whites

Pathology

• multiple harmatomatous neoplasms of ectodermal, mesodermal & endodermal origin in many organ systems including the breast (70%), thyroid (40-60%), skin, CNS (40%), gastrointestinal tract
• trichilemmomas & mucocutaneous papillomatosis (99%) are hallmarks of Cowden's disease
• trichilemmomas show differentiation towards the outer root sheath cells of the hair follicles
• multiple biopsies may be required to obtain characteristic histopathology
• oral lesions are fibromas
• dysplastic gangliocytoma of the cerebellum Lhermitte-Duclos disease variant)

Genetics

• autosomal dominant
• associated with defects in PTEN & BMPR1A

Clinical-manifestations

• skin lesions:

• trichilemmomas

• portend the onset of breast & thyroid cancers
• skin-colored pink or brown papules with the appearance of flat warts
• distribution: central areas of the face, perioral areas, lips near the angles of the mouth & ears
• lesions may be extensive & disfiguring

• tranlucent punctate keratosis of palms & soles
• hyperkeratotic, flat-topped papules on the dorsal aspect of the hands & forearms
• lipomas & angiomas (rare)

• mucous membranes

• papules of the gingival, labial & palatal surfaces

• whiter than surrounding mucosa giving a "cobblestone" appearance

• papillomas of the buccal mucosa & tongue
• oral fibromas
• squamous cell carcinoma of the tongue may occur
• basal cell carcinoma may occur in the anal area

• breasts

• fibrocystic disease
• fibroadenoma
• adenocarcinoma (20%)
• gynecomastia in males

• thyroid

• goiter
• adenomas
• thyroglossal duct cysts
• follicular adenocarcinoma (8%)

• GI tract

• harmatomatous polyps throughout the intestine, but especially in the colon
• adenocarcinoma (rare)

• female genital tract

• ovarian cysts
• menstrual irregularities
• uterine carcinoma (rare)

• male genital tract - carcinoma of the prostate (rare)
• musculoskeletal system

• craniomegaly
• kyphoscoliosis
• high-arched palate

• CNS involvement

• mental retardation
• seizures
• neuromas
• ganglioneuromas
• meningiomas of the ear canal
• cerebellar signs

Laboratory

• thyroid scan
• skin biopsy

Radiology

• mammography to rule out breast cancer

Complications

• adenocarcinoma of the breast (20%)
• follicular adenocarcinoma, follicular thyroid carcinoma (8%)

Differential-diagnosis

• multiple syringomas
• multiple angiofibromas
• tuberous sclerosis
• multiple trichilemmomas
• verruca plana ( flat warts)
• Muir-Torre syndrome
• lipoid proteinosis
• multiple endocrine neoplasia ( MEN) IIb

Management

• follow closely for evidence of breast or thyroid cancer
• genetic counseling
• prognosis - tumors continue to develop throughout life

More General Terms

• intestinal polyposis syndrome; hereditary colorectal carcinoma
• skin disease (dermatologic disorder, dermatopathy, dermatosis)

Additional Terms

• chromosome 10q23 deletion syndrome
• protein tyrosine phosphatase PTEN

Internet Database

OMIM: 158350

References

1. Liaw D et al, Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997 May;16(1):64-7. PMID: [1]
2. Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 508-511
3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 171
4. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998

Cowden's disease; multiple hamartoma syndrome including Lhermitte-Duclos disease (cerebelloparenchymal disorder)