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Multiple gastrointestinal polypoid lesions including a fundic gland polyp, a gastric hyperplastic/hamartomatous polyp, a tubular adenoma, several colonic ganglioneuromas and hamartomatous polyps, and a colonic intramucosal lipoma. One month prior, the patient had been diagnosed with a PTEN mutation. These findings are consistent with Cowden syndrome.


Cowden syndrome (CS) is an autosomal dominant disorder caused by germline mutations in the phosphatase and tensin homolog (PTEN) gene, which results in the development of multiple hamartomatous lesions. It is the most common PTEN hamartoma tumor syndrome (PTHS), a group of PTEN-mutated syndromes predisposing to neoplasia and encompassing other disorders such as Bannayan-Riley-Ruvalcaba syndrome. CS is a hamartomatous polyposis syndrome, part of a category which also includes Peutz-Jeghers Syndrome and Juvenile Polyposis Syndrome. Patients with these syndromes have increased risk for cancer; specifically, patients with CS are at increased risk for breast, thyroid, and endometrial cancers. CS patients most commonly present with mucocutaneous lesions and the estimated incidence of CS is around 1 in 200,000 – 250,000.

Prior to the identification of the PTEN mutation, the clinical diagnosis of CS was based on the presence of major and minor criteria as outlined by the International Cowden Consortium (ICC) and the National Comprehensive Cancer Network (NCCN), which included the requirement of mucocutaneous lesions, in addition to, the presence of thyroid, breast, and endometrial neoplasms or hamartomatous gastrointestinal (GI) polyps, mental retardation, and macrocephaly. More recent criteria have been proposed for PTEN hamartoma tumor syndrome and include a similar set of major criteria, expanded to include other syndromes within the spectrum of PTEN hamartoma tumor syndrome. Because PTEN mutations are only detected in up to 35% of patients meeting CS criteria, clinical criteria including histopathologic analysis remain essential to the diagnosis.

Patients with CS commonly have hamartomatous polyps of the GI tract, yet inflammatory, hyperplastic, or adenomatous polyps may also be found. Various studies have examined the histopathologic features of GI polyps found in these patients so as to distinguish CS patients from other patients with syndromic or sporadic polyps. One group suggested that CS patients have polyps that are most often colonic, small, and sessile and frequently found with ganglion cells in the lamina propria or mucosal fat. Interestingly, another group found that patients with CS have a higher likelihood of intramucosal lipomas. In addition to polyps, other common GI findings include ganglioneuromas and esophageal glycogenic acanthosis. Previously, there was no association of CS with colorectal cancer; however, more recently some studies have shown that these patients actually have a higher risk. These findings, in parallel with the prevalence of colon polyps, have prompted new recommendations for colorectal cancer surveillance.

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