THU533 Cowden Syndrome: A Rare Disease With A Lasting Impact

Abstract

Abstract Disclosure: C.S. Hastings: None. S.A. Patrick: None. D. James: None. Introduction: Cowden Syndrome (CS) is a genetic condition caused by an autosomal dominant mutation in the phosphatase and tensin homolog (PTEN) tumor suppressor gene. The prevalence of CS is approximately one in 200,000 and onset is typically in the second decade of life. It is characterized by multiple benign or malignant skin tumors, non-medullary thyroid cancer, breast carcinoma, endometrial carcinoma, gastrointestinal hamartomas, renal cell carcinoma, and/or developmental delay. CS is typically underdiagnosed due to the variety of phenotypic presentations. Case Description: We present a case series of Cowden Syndrome. The first patient was a 51-year-old male with follicular thyroid cancer status post radiation and thyroidectomy, multiple gastrointestinal polyps, trichilemmomas, and an extensive family history of cancer. These factors led to an increased suspicion for CS. The patient underwent genetic testing for PTEN mutations in 2022 and was heterozygous for the c.723dupT pathogenic PTEN mutation as well as p.S598L mutation. The second patient was an 18-year-old female with developmental delay, autoimmune hypothyroidism, multinodular goiter who presented with an increasing number of thyroid nodules on annual thyroid ultrasounds. Her thyroid nodule biopsy revealed follicular and papillary thyroid carcinoma requiring total thyroidectomy. Her mother had a known history of CS. Genetic testing revealed she was heterozygous for the p.S1701 pathogenic mutation in the PTEN gene. Diagnosis of CS involves a combination of family history, presence of mucocutaneous lesions, and either thyroid, breast, or endometrial carcinoma. Given the higher likelihood of cancers in these patients, routine screening for thyroid, breast, kidney, and colon cancers should begin at an earlier age. Treatment includes topical agents such as fluorouracil or excision surgery for skin lesions. Treatment of malignancy is similar to sporadic counterparts and involves systemic immunosuppressants, chemotherapy, or surgery. Conclusion: Cowden Syndrome is a rare genetic condition resulting in tumors in a variety of organ systems, placing patients at a higher risk of malignancy. A strong family history of malignancy, as well as skin, breast, GI, or thyroid findings should prompt further investigation. Collaboration between dermatology, oncology, gastroenterology, endocrinology, and neurology is essential for successful treatment. Routine screening for these patients includes thyroid studies every 3-4 months, thyroid ultrasound yearly, colonoscopy every two years, and renal CT or MRI yearly. Early diagnosis of the condition is pivotal for close cancer surveillance and management. Presentation: Thursday, June 15, 2023