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Medical Science Monitor Basic Research


Unexpected Pathogenic RET p.V804M Variant Leads to the Clinical Diagnosis and Management of Medullary Thyroid Carcinoma

Unusual clinical course

Arezou A. Ghazani, Katelyn M. Breen, Meaghan Dwan, Justine A. Barletta, Donna R. Vatnick, Samantha M. Stokes, Caroline Block, Gerard M. Doherty, Aviva Y. Cohn, Ellen Marqusee, Judy E. Garber, Huma Q. Rana

USA Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

Am J Case Rep 2020; 21:e927415

DOI: 10.12659/AJCR.927415

Available online: 2020-11-06

Published: 2020-12-27


BACKGROUND: RET p.V804M is a known activating oncogenic variant that confers an increased risk for medullary thyroid carcinoma (MTC). Based on age-specific penetrance, the American Thyroid Association (ATA) categorizes this variant as posing moderate risk. Therefore, ATA guidelines endorse prophylactic thyroidectomy for carriers in childhood (by age 5-10 years) or adulthood, or when the serum calcitonin level becomes elevated. The recommendation for thyroidectomy is increasingly controversial due to the recently reported low penetrance of the RET p.V804M variant in a large unbiased ascertainment cohort.
CASE REPORT: We describe the unexpected identification of this variant in a 62-year-old woman undergoing broad, multigene cancer panel testing for her personal and family history of breast cancer. There was no known family history of MTC. Biochemical screening prompted by the RET p.V804M result revealed a mildly elevated serum calcitonin. Pathology examination of her thyroidectomy specimen revealed multifocal medullary thyroid microcarcinoma; her sibling’s prophylactic thyroidectomy after a RET p.V840M-positive result similarly revealed early-stage MTC.
CONCLUSIONS: This report demonstrates the value of genetic counseling, shared decision-making, cascade testing, and timely thyroidectomy in the management of a patient with an unexpected RET p.V804M result.

Keywords: Multiple Endocrine Neoplasia Type 2a, Proto-Oncogene Proteins c-ret, Thyroid Neoplasms, Thyroidectomy