Evaluation of breast involvement in relation to Cowden syndrome: a radiological and clinicopathological study of patients with PTEN germ-line mutations

Abstract

We describe the clinical, radiological, and pathological findings of the diverse benign and malignant breast neoplasms found in association with Cowden syndrome. Patients with Cowden syndrome had a substantially increased risk of breast carcinoma. We find that 33% of the patients in our study population with Cowden disease have developed breast carcinoma to date. An association between Cowden disease and multiple tubular adenomas or breast hamartomas was found in two patients, suggesting a genetic origin. PTEN germ-line mutations were found in all four patients presenting with relevant benign or malignant breast pathology. We also assess the value of specific diagnostic tools used in the surveillance management. Screening mammography was useful in the diagnosis of small, high-grade carcinomas.

Cowden Syndrome Presenting as Breast Cancer: Imaging and Clinical Features

“…Nipple or areolar malformations, fibroadenomas, proliferative fibrocystic diseases, ADH or lobular carcinoma in situ have been described for the benign breast disease (1). Multiple tubular adenomas or bilateral exuberant hamartomas and fibroadenomas were reported in patients with Cowden syndrome (5, 10), similar to our case. Therefore, the presence of bilateral extensive breast lesions in very young women should elicit the possibility of an underlying genetic disease that is associated with an increased risk of breast cancer such as the Cowden syndrome.…”

“…It has been reported to be susceptible to breast cancer, thyroid cancer, endometrium cancer, renal cell cancer, colorectal cancer, and melanoma (3, 4, 5, 6, 7). The condition was first described in 1963 and was named following the patient's name (8).…”

“…The diagnosis is based on pathognomonic clinical features, however, the Cowden syndrome is manifested with highly variable symptoms and signs and might be underdiagnosed. Notably, the characteristic mucocutaneous hamartomatous lesions are generally present prior to the development of internal malignancies (5). …”

Thyroid Pathology inPTEN-Hamartoma Tumor Syndrome: Characteristic Findings of a Distinct Entity

“…Very few germline mutations have been reported in exon 1, and none in exon 9 (25). Seventyfive percent of the germline mutations result in truncated protein, lack of protein, or dysfunctional protein (26)(27)(28)(29)(30)(31).…”

Head circumference in the clinical detection of PTEN hamartoma tumor syndrome in a clinic population at high-risk of breast cancer

“…Relatives of these individuals should also be screened for inherited susceptibility to cancer. The presence or absence of diagnostic features can guide management of individuals with potential increased risk [4,10].…”