Cowden's disease; multiple hamartoma syndrome including Lhermitte-Duclos disease (cerebelloparenchymal disorder)
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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 (70-85%), thyroid (40-60%), skin, CNS (40%), kidney (34%), endometreium (28%) gastrointestinal tract
- trichilemmomas (tan facial papules) & mucocutaneous papillomatosis (cobblestoning) & acral ketatoses are hallmarks of Cowden's disease (99%)
- 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)
- macrocephaly & intellectual disability[7]
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
- translucent punctate keratosis of palms & soles
- hyperkeratotic, flat-topped papules on the dorsal aspect of the hands & forearms
- lipomas & angiomas (rare)
- trichilemmomas
- 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
- papules of the gingival, labial & palatal surfaces
- breasts
- thyroid
- 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
Laboratory
Radiology
- annual thyroid ultrasonography beginning at age 18 years[7]
- colonoscopy beginning at age 35 years
- kidney ultrasonography beginning at age 40 years
- annual mammogram beginning at ages 30-35 years
- annual endometrial cancer ultrasonography beginning at ages 30-35 years[7]
Complications
- adenocarcinoma of the breast (20%)
- follicular adenocarcinoma, follicular thyroid carcinoma (8%)
- gastrointestinal polyps[4]
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
- annual skin checks
- genetic counseling
- prognosis - tumors continue to develop throughout life
More general terms
Additional terms
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/9140396
- ↑ Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 508-511
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 171
- ↑ 4.0 4.1 Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 18. American College of Physicians, Philadelphia 1998, 2015, 2018.
- ↑ 5.0 5.1 Fiala KH, James WD (images) Medscape: Cowden Disease (Multiple Hamartoma Syndrome) http://emedicine.medscape.com/article/1093383-overview
- ↑ 6.0 6.1 DermNet NZ. Cowden disease (images) http://www.dermnetnz.org/systemic/cowden.html
- ↑ 7.0 7.1 7.2 7.3 Bhanot A, Harrell K, Levin J. Treatment of Trichilemmomas With Topical Sirolimus. JAMA Dermatol. Published online January 4, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36598777 https://jamanetwork.com/journals/jamadermatology/fullarticle/2800121
Patient information
Cowden's disease patient information