Cowden Syndrome: Imaging Review and Cancer Surveillance

Cowden syndrome (CS) is a rare autosomal-dominant inherited variant of <i>PTEN</i> (phosphatase and tensin homolog gene) hamartoma tumor syndrome caused by mutations to the <i>PTEN</i> tumor suppressor gene, leading to activation of the PI3K/AKT/mTOR intracellular signaling pathway. Patients with this syndrome present with multisystem hamartomatous lesions and are particularly predisposed to developing malignancies, including breast, thyroid, renal, endometrial, and colorectal malignancies. Mucocutaneous lesions, especially trichilemmomas, and macrocephaly are commonly seen in the 2nd decade of life and usually manifest before the development of malignancies. In children, clinical manifestations such as intellectual disability and gastrointestinal polyps may arise and may prompt early investigation and diagnosis. Major features of CS include Lhermitte-Duclos disease, breast cancer, endometrial cancer, thyroid carcinoma, macrocephaly, and gastrointestinal hamartomas. Other features that are considered part of the minor clinical diagnostic criteria include colorectal cancer, esophageal glycogenic acanthosis, lipomas, renal cell carcinoma, testicular lipomatosis, and vascular anomalies. Comprehensive evaluation including clinical and genetic assessment and imaging is essential for early diagnosis and management. Given the increased risk of developing malignancies, surveillance strategies have been routinely updated and recommended by the National Comprehensive Cancer Network. Important cancer surveillance imaging strategies include mammography, MRI of the breast, and US of the thyroid and kidneys, although other manifestations are routinely assessed with CT and MRI. In this article, the genetics and molecular pathogenesis, clinical manifestations, imaging features, and most up-to-date surveillance recommendations of CS are reviewed. ^©RSNA, 2026 Supplemental material is available for this article.