SAT512 Familial Thyroid Cancer With Negative Pre-operative Genetic Screening

Abstract

Abstract Disclosure: A. Yuen: None. R. Owen: None. S.R. Saul: None. Today it is estimated that the etiology of approximately 90% of thyroid cancer cases are understood, compared to only 25% in the 1990s. However, despite the encouraging progress with oncogenetic screening panels, thyroid cancer-specific testing are not always included. We present a family with 3 generations of thyroid cancer with negative genetic screening ultimately found to have BRAF mutation post-operatively. A 62-year-old woman of Brazilian descent with a medical history of papillary thyroid cancer (PTC) status-post total thyroidectomy presented to clinic. The patient’s PTC was diagnosed 10 years prior when she presented with dysphagia and vocal changes. A thyroid ultrasound revealed a right-sided 2.3 cm solid mass and a fine needle aspiration confirmed PTC. The patient underwent a total thyroidectomy with pathology verifying a PTC with lymphovascular invasion and minimal local extrathyroidal extension as well as a 0.4 cm microcarcinoma in the left lobe. Post-operatively, she received 100 millicurie of radioactive iodine and was started on levothyroxine. Interestingly, the patient reported as strong family history of varying cancers, notably colon, breast, uterine, and thyroid. Her mother was diagnosed at 55-years-old with thyroid cancer that metastasized to her lungs and her daughter was found to have PTC at age 31-years-old. Additionally, the daughter has two teenage sons, both with multiple thyroid nodules who are currently being followed by a pediatric endocrinologist. Given this history, the patient and her daughter both completed genetic testing which was negative for the 42 known mutations associated with an increased risk of cancer, though they both were heterozygous for a mutation of uncertain clinical significance in the MSH2 gene, specifically the c.959C>G (pT320S). Although the standard genetic panel was negative, due to concern for a hereditary mutation, the patient’s thyroidectomy specimen was sent for analysis and confirmed a BRAF mutation. Subsequently, the patient’s daughter also underwent completion thyroidectomy and was found to have the BRAF mutation. This family demonstrated likely hereditary BRAF-associated PTC across 3 generations with children in the fourth generation having known thyroid nodules, generally rare in youth. Although the patient and her daughter were both tested for genetic mutations linked to cancers, neither were positive and it was only after undergoing surgery that they were found to have the BRAF mutation. Although BRAF mutations account for 45% of PTC and are the most commonly associated mutation, they are not commonly included in pre-operative screening or the standard oncogenetic screening panel. Developing a thyroid cancer specific mutation panel to screen family members of patients with thyroid cancer will be an important step in determining these individuals’ best management. Presentation Date: Saturday, June 17, 2023