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Cowden syndrome (CS) is a rare, autosomal dominant multisystem disorder characterized by multiple hamartomas and an increased risk of several malignancies.

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• It belongs to the spectrum of PTEN hamartoma tumor syndromes (PHTS).

Cowden syndrome, also known as multiple hamartoma syndrome or PTEN hamartoma tumor syndrome, is a rare autosomal-dominant condition caused by mutations of the PTEN tumor suppressor gene, leading to uncontrolled cell proliferation, which manifests as multisystem hamartomas and malignancies. Patients with Cowden syndrome are at increased risk for breast, thyroid, colon, kidney, and endometrial malignancies. Ciléin Kearns, Artibiotics, Copyright © 2022 Balthazar P, Klontzas ME, Heng LXX, Kearns C. Cowden Syndrome. RadioGraphics. 2022;42(2):E44-E45. doi:https://doi.org/10.1148/rg.210230

Etiology

Genetic basis:

• The PTEN gene functions as a tumor suppressor, regulating cell cycle progression and apoptosis via the PI3K-AKT-mTOR pathway.
• Mutations result in dysregulated cellular growth and proliferation.

Clinical Features

![CS is a rare, autosomal-dominant disorder caused by germline mutations in the phosphatase and tensin homolog on chromosome 10 tumor-suppressor gene that manifests with hamartomatous growths involving all 3 embryonic origins. There is considerable heterogeneity in the clinical presentation; however, mucocutaneous lesions are characteristic with multiple facial trichilemmomas (Figure A) and cobblestoning of the oral mucosa owing to papillomatosis (Figure B) being pathognomonic. Glycogenic acanthosis of the esophagus occurring in conjunction with colon polyps also is considered diagnostic for CS. Polyps of many different histologic types (hamartomatous, hyperplastic, inflammatory, lipomatous, fibromatous, and adenomatous) are found throughout the gastrointestinal tract in up to 85% of CS patients.

Stanich PP, Francis DL, Sweetser S. The Spectrum of Findings in Cowden Syndrome. Clinical Gastroenterology and Hepatology. 2010;9(1):e2-e3. doi:https://doi.org/10.1016/j.cgh.2010.07.003](attachment:9f20b34d-bf0a-4cfe-887c-2ff3e46f20b7:gr1_lrg.jpg)

CS is a rare, autosomal-dominant disorder caused by germline mutations in the phosphatase and tensin homolog on chromosome 10 tumor-suppressor gene that manifests with hamartomatous growths involving all 3 embryonic origins. There is considerable heterogeneity in the clinical presentation; however, mucocutaneous lesions are characteristic with multiple facial trichilemmomas (Figure A) and cobblestoning of the oral mucosa owing to papillomatosis (Figure B) being pathognomonic. Glycogenic acanthosis of the esophagus occurring in conjunction with colon polyps also is considered diagnostic for CS. Polyps of many different histologic types (hamartomatous, hyperplastic, inflammatory, lipomatous, fibromatous, and adenomatous) are found throughout the gastrointestinal tract in up to 85% of CS patients.

Stanich PP, Francis DL, Sweetser S. The Spectrum of Findings in Cowden Syndrome. Clinical Gastroenterology and Hepatology. 2010;9(1):e2-e3. doi:https://doi.org/10.1016/j.cgh.2010.07.003

Neoplasms (increased lifetime risk**):**

Radiology

https://doi.org/10.1148/rg.210230

![Multisystem findings in Cowden syndrome. (A) Photograph shows multiple keratotic papules at the palmar surface of the hand, findings compatible with acral keratosis. (B) Spot endoscopic image shows multiple whitish plaque-like esophageal nodules, findings consistent with glycogenic acanthosis. (C) Coronal chest CT image shows esophageal wall plaquelike irregularity due to glycogenic acanthosis. (D) Longitudinal US images of the bilateral testes show multiple small nonshadowing intratesticular hyperechoic masses, compatible with testicular lipomatosis. The testes are normal in size and contour. (E) Coronal T1-weighted postcontrast MR image of the brain shows hypointense non-enhancing striation in the right cerebellum. (F) Axial FLAIR MR image of the brain shows a hyperintense right cerebellar ill-defined lesion without significant edema, consistent with Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma).

Balthazar P, Klontzas ME, Heng LXX, Kearns C. Cowden Syndrome. RadioGraphics. 2022;42(2):E44-E45. doi:https://doi.org/10.1148/rg.210230](attachment:0787a74a-9fcc-4171-af81-3d624f0e3a1b:images_large_rg.210230fig3.jpeg)

Multisystem findings in Cowden syndrome. (A) Photograph shows multiple keratotic papules at the palmar surface of the hand, findings compatible with acral keratosis. (B) Spot endoscopic image shows multiple whitish plaque-like esophageal nodules, findings consistent with glycogenic acanthosis. (C) Coronal chest CT image shows esophageal wall plaquelike irregularity due to glycogenic acanthosis. (D) Longitudinal US images of the bilateral testes show multiple small nonshadowing intratesticular hyperechoic masses, compatible with testicular lipomatosis. The testes are normal in size and contour. (E) Coronal T1-weighted postcontrast MR image of the brain shows hypointense non-enhancing striation in the right cerebellum. (F) Axial FLAIR MR image of the brain shows a hyperintense right cerebellar ill-defined lesion without significant edema, consistent with Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma).

Balthazar P, Klontzas ME, Heng LXX, Kearns C. Cowden Syndrome. RadioGraphics. 2022;42(2):E44-E45. doi:https://doi.org/10.1148/rg.210230

Lhermitte–Duclos Disease (LDD)