Background
Cowden syndrome (CS) is a autosomal dominant inherited syndrome. These patients are characterized by multiple hamartomas occurring in the skin, breast, thyroid, gastrointestinal tract, endometrium, and brain. Patients do have an increased risk of experiencing malignant tumors with the most common ones are breast, endometrial, and thyroid cancer.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Multiple hamartoma syndrome
PATHOGENESIS CHARACTERIZATION Identification of a PTEN mutation in a family with Cowden syndrome and Bannayan-Zonana syndrome J Am Acad Dermatol 2001;44:183-7
Single kindred with individuals manifesting both CS and BZS phenotypes (CS/BZS overlap family)
Novel mutation in PTEN by DNA sequencing.
The PTEN gene (phosphatase and tensin homolog deleted from chromosome 10) has been identified as the susceptibility gene for CS and BZS
Also known as MMAC1 (mutated in multiple advanced cancers) or TEP1 (TGF-regulated and e pithelial cell-enriched p hosphatase), is a tumor suppressor gene located on chromosome 10q23.28-30 It has 9 exons that encode a protein of 403 amino acids.
The presence of individuals with CS and BZS within the same family, and moreover the identification of identical PTEN gene mutations in these individuals, suggest that these two syndromes represent different phenotypic expressions of one disease
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION General VARIANTS BRAIN 38% of CS patients have macrocephaly BREAST Fibrocystic breast disease
Fibroadenomas
Carcinoma (30% to 50% of female patients)ENDOMETRIUM Endometrial carcinoma GI Intestinal polyposis SKIN Manifest by the late teens to twenties
Present in 99% of patients with CSThese most common mucocutaneous findings are:
Trichilemmomas
Oral papillomatoses
Acral and palmoplantar keratoses.TESTICLE
- Testicular lipomatosis in Cowden's syndrome.
Woodhouse JB, Delahunt B, English SF, Fraser HH, Ferguson MM.
1Department of Urology, Christchurch Hospital, Christchurch, New Zealand.
Mod Pathol. 2005 Sep;18(9):1151-6. Abstract quote
Cowden's syndrome is either familial or sporadic and is associated with the predominantly postpubertal development of a variety of cutaneous, stromal and visceral neoplasms. The syndrome is associated with mutations of the PTEN gene and is closely related to Bannayan's syndrome in which macrocephaly and benign tumors, especially lipomas and hemangiomas are pathognomic. In PTEN knockout mice testicular tumors have been reported and for this reason we felt it prudent to examine the testes of our patients with genetically proven Cowden's syndrome.
Seven of eight patients who underwent testicular ultrasound were found to have diffuse bilateral hyperechoic lesions. Four patients consented to testicular biopsy and on histological examination multiple foci of adipocytes were found within the testicular interstitium, with no evidence of dysplasia or preclinical malignancy.
Immunohistochemical assessment of adipocytes suggested a stromal derivation without evidence of metaplasia from Leydig cells. In one case there was focal atrophy of seminiferous tubules, while in two others there was nodular periorchitis of the tunica albuginea. Biochemical evaluation of testicular function (luteinizing hormone, follicle-stimulating hormone, testosterone, sex hormone binding globulin and free androgen index), prostate-specific antigen and testicular tumor markers were normal, while seminal fluid analysis showed only minor abnormalities.
The high incidence of testicular lipomatosis in our adult subjects suggests this to be an important diagnostic criterion for Cowden's syndrome.THYROID Thyroid adenomas, goiter
Carcinoma (3% to 10% of all CS patients)
HISTOPATHOLOGICAL VARIANTS CHARACTERIZATION SKIN SCLEROTIC FIBROMA Pleomorphic sclerotic fibroma: a case report and literature review.
Chen TM, Purohit SK, Wang AR.
Departments of Pathology and Laboratory Medicine (A.R.W.) and Surgery (S.K.P.), Tulane University Health Sciences Center, New Orleans, Louisiana; and Baylor College of Medicine, Houston, TX, U.S.A. (T.M.C.).
Am J Dermatopathol 2002 Feb;24(1):54-8 Abstract quote Pleomorphic sclerotic fibroma is a benign neoplasm exhibiting features of sclerotic fibroma and pleomorphic fibroma. We report another such case. The tumor presented as a firm, 0.5-cm, flesh-colored papule on the forehead of a 72-year-old white man for an unknown duration.
Histologic examination revealed a neoplasm in which the superficial portion showed features of a pleomorphic fibroma, the deeper portion showed features of a sclerotic fibroma, and a transitional area was present in between.
We propose that pleomorphic fibroma, sclerotic fibroma, and pleomorphic sclerotic fibroma form a spectrum. Pleomorphic sclerotic fibroma may be used as a broad diagnostic term to encompass the spectrum.
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Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
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