Cowden Syndrome

Epidemiology and Etiology:

· PTEN mutation (part of the PTEN hamartoma tumour syndrome – PHTS)

· PTEN is a dual-specificity phosphatase

· The major phosphatase in the PI3K/Akt pathway

· Downregulates the PI3K/Akt pathway

· Causes G1 arrest and apoptosis

· Autosomal dominant

· Late 20’s presentation

Common sites:

· Multiple hamartomas of organs derived from all 3 germinal layers

· GI tract:

· Hamartomatous polyps (similar to juvenile polyps)

· carcinoma

· Mucocutaneous:

· Facial trichilemmomas (usually)

· Acral keratoses

· Oral papillomas

· Breast:

· carcinoma (25-50% lifetime) (38-46y avg age)

· Fibrocystic disease

· Thyroid:

· Follicular carcinoma (10% lifetime)

· Uterus:

· Endometrial carcinoma (5-10% lifetime)

· leiomyoma

· GU:

· Renal cell carcinoma

· Brain:

· Cerebellar dysplastic gangliocytoma (pathognomonic)

· Soft tissue:

· Lipomas

· fibromas

Gross features:

· Macrocephaly (usually)

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

·

Other features:

· Autism (~20% of patients with autism and macrocephaly have germline PTEN mutations

· Mental retardation

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.

· Gene Reviews website