Cowden Syndrome (CS) is an autosomal dominant disorder characterized by hamartomatous growth in several organs and by an increased risk of
malignancies, which makes its recognition essential to undertake risk reduction measures. Although the involvement of gastrointestinal tract is extremely common, awareness of this entity among gastroenterologists appears limited. We report on two unrelated patients: a 46-year-old male and a 38-year-old woman, who were referred to the Genetic Clinic because of the endoscopic finding of multiple colorectal
polyps. Despite both displayed striking clinical (and, in the first case, familial) manifestations of
Cowden Syndrome (
PTEN Hamartoma Tumor Syndrome-PHTS), they had not been recognized before. Diagnosis of PHTS was confirmed by the detection of causative PTEN variants. Pathological examination of the
polyps showed multiple histology types: hyperplastic, juvenile, serrated and lymphoid. Hyperplastic
polyps analyzed from both patients failed to show BRAF V600E and KRAS
codon 12/13 mutations, which provides evidence against their potential to evolve to
colorectal cancer through the serrated pathway. We then reviewed the literature on gastrointestinal
polyps detected in patients with
Cowden Syndrome, in order to provide a comprehensive scenario of presentations: among a total of 568 patients reported in the literature, 91.7 % presented with colon
polyps, with 63.0 % having two or more different histological types of
polyps; besides, 58.5 % had extra-
colonic polyps (located either in stomach and/or in small intestine). Finding multiple
polyps with mixed and/or unusual histology should alert gastroenterologists and pathologists about the possible diagnosis of
Cowden Syndrome and prompt the search for other manifestations of this condition in the patient.