Challenges in the management of a patient with Cowden syndrome: case report and literature review

Cowden syndrome (CS) is an uncommon disorder with an estimated incidence of 1 per 200,000 of the population, characterized by germline mutations in the tumor suppressor gene PTEN [1,2]. CS is associated with highly variable symptoms and signs, meaning that it might be underdiagnosed; in addition, approximately 20% of CS patients have no identified genetic explanation of their phenotypic features [3].CS is characterized by multiple hamartomas in a variety of tissues and indicates an increased risk of developing malignancies. In female patients the syndrome is associated with up to 50% lifetime risk of developing breast cancer, 5-10% risk of developing endometrial cancer, and 10% lifetime risk of developing follicular thyroid cancer [4]. In recent reports the elevated lifetime cancer risk in Cowden syndrome patients or in individuals with germline PTEN mutations is up to 85% for breast cancer, up to 35% for thyroid cancer, and up to 28% for endometrial cancer [5,6]. Lifetime cancer risks are now extending to kidney cancer and colorectal cancer (up to 33% and 16%, respectively).Other features of the disorder include macrocephaly, gastrointestinal polyps, benign breast, thyroid and endometrial manifestations, and characteristic mucocutaneous lesions. The diagnosis of CS in most cases is primarily based on the presence of mucocutaneous features, estimated to have 99% penetrance before the age of 30 [7]. A correlation between an identified PTEN mutation and breast cancer diagnosis in CS has been reported [3]. Breast cancers are most often diagnosed in CS patients at the age of 38-46 [8]. 34% of female CS patients diagnosed with breast cancer had bilateral diseases [5].The proband is a female born in Latvia in 1973. She has a remarkable medical history from the age of 32 when she underwent total thyroidectomy due to a benign nodular goiter. Cavernous angioma of the right temporal lobe (2.1 × 1.7 cm) was present on brain MRI with contrast and liver angioma was detected at a