1586 A Classic Presentation of Cowden Syndrome

Abstract

INTRODUCTION: Cowden syndrome (CS) is a rare autosomal dominant hereditary multiple hamartoma syndrome characterized by benign and malignant tumors. CS is one of the four subtypes of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS). The National Comprehensive Cancer Network utilizes consensus diagnostic criteria, where one must have ≥3 major criteria or 2 major plus 3 minor criteria. Major criteria include breast cancer, endometrial cancer, follicular thyroid cancer, GI hamartomas including ganglioneuromas, Lhermitte-Duclos disease, macrocephaly, macular pigmentation of the glans penis, and multiple mucocutaneous lesions. Minor criteria include autism, colon cancer, esophageal glycogenic acanthoses, lipomas, intellectual disability, renal cell carcinoma, testicular lipomatosis, papillary thyroid cancer, thyroid structural lesions, and vascular anomalies. CASE DESCRIPTION/METHODS: A 59-year-old male with macrocephaly presented for a screening colonoscopy. He was found to have 30 polyps ranging in size from 3-15 mm. Pathology revealed serrated adenomas, hyperplastic polyps and moderately differentiated invasive adenocarcinoma arising in a tubular adenoma. Subsequent PET/CT revealed marked enlargement and heterogeneity in the thyroid gland. He underwent a total colectomy with ileorectal anastomosis and ultimately a total thyroidectomy. The resected colon showed adenomatous polyps, multiple lipomas, and a ganglioneuroma. Pathology from the thyroid revealed a 2.5 cm nodule with follicular carcinoma and a 6 mm nodule with papillary micro-carcinoma, follicular variant. Our patient met 3 major criteria (macrocephaly, GI hamartomas including ganglioneuromas, follicular thyroid carcinoma) and 1 minor criterion (colon cancer). The clinical presentation prompted genetic testing. DISCUSSION: Early onset colorectal cancer has been reported in patients with CS due to malignant transformation of adenomatous and hamartomatous polyps. Management includes annual thyroid ultrasound, renal ultrasound at age 40 every 1-2 years, dermatologic assessment, and discussion regarding risk to relatives. Colonoscopy is recommended at age 35 and then at least every 5 years; more frequent in patients who are symptomatic, have family history of colon cancer, personal history of polyps or colon cancer. Recognition of pertinent medical history, family history and physical manifestations are critical for accurate diagnosis, risk assessment, genetic testing and medical management.