Marcos Vinícius Sampaio Vieira was 35 when a routine medical visit uncovered three thyroid nodules, including one measuring four centimeters. His hormone levels were normal, and doctors initially suspected a goiter. A biopsy, requested because Vieira remained concerned, revealed cancer. Yet the tumor was not fully identified until after his thyroid was removed: it was medullary thyroid carcinoma, a rare and potentially aggressive disease that can arise from inherited changes in the RET gene.
The diagnosis appeared to mark the end of the crisis. In 2005, Vieira underwent thyroid removal followed by cervical lymph-node dissection, an operation designed to determine whether the cancer had spread beyond the thyroid. No metastases were found, and he returned to his life while continuing regular medical surveillance. Three years later, however, abnormal blood-test results led to imaging that detected metastatic lesions in his liver. He later developed tumors in his spine, one of which was treated locally with cryoablation, a technique that destroys tumor tissue by exposing it to extremely low temperatures.
Vieira’s illness also raised a critical question for his family. Medullary thyroid carcinoma can occur sporadically, but a substantial proportion of cases are hereditary. Relatives were tested to determine whether Vieira’s brother, two children, and two nieces carried the same genetic risk. The first tests were negative, offering the family temporary reassurance. That confidence disappeared when Vieira’s brother developed visible thyroid nodules. Testing at specialized referral centers subsequently showed that the earlier results had been false negatives.
In 2010, while volunteering with a research group at the São Paulo State Cancer Institute, Vieira underwent molecular testing that identified an inherited mutation in RET. The gene encodes a receptor tyrosine kinase, a protein involved in transmitting growth and survival signals inside cells. Certain activating RET mutations can drive the abnormal proliferation of thyroid cells and are associated with multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. The particular hereditary alteration in Vieira’s family was considered to have very high penetrance, meaning that most carriers would be expected to develop the disease during their lifetimes without preventive treatment.
The genetic result transformed the family’s medical strategy from monitoring disease to preventing it. Vieira’s children were only seven and ten years old when testing showed that they carried the mutation. Because hereditary medullary thyroid carcinoma can begin silently and may become more difficult to cure once it spreads, specialists recommended prophylactic total thyroidectomy. The operation removes the tissue in which the cancer is expected to arise. Vieira’s niece also underwent the procedure. Today, the children are adults and remain free of medullary thyroid carcinoma; both are pursuing medical careers.
“Medicine has changed profoundly with advances in molecular biology,” says Ana Amélia Fialho de Oliveira Hoff, head of Endocrinology at the cancer institute and the University of São Paulo Medical School. The discovery of RET’s role in hereditary thyroid cancer in 1993 helped establish a model for precision oncology: identifying a molecular risk before symptoms appear and matching the intervention to that risk. In families with pathogenic RET variants, genetic testing can determine which relatives require intensive surveillance or preventive surgery and which relatives can avoid unnecessary procedures.
Vieira’s story is the central clinical case in a new article published in CA: A Cancer Journal for Clinicians. Titled “Medullary thyroid carcinoma and RET molecular testing: A virtual tumor board on clinical decision-making,” the paper reviews the evolution of RET testing and examines how molecular information affects diagnosis, surgery, follow-up, and treatment. The authors used a “Big Picture Evidence” approach, combining decades of research with the perspectives of specialists in genetics, endocrinology, surgery, oncology, and pathology, as well as the patient’s own experience.
The review emphasizes that genetic testing is not only a laboratory exercise. A result can alter decisions for an entire family, reveal the likely cause of cancer in previous generations, and guide treatment for relatives who have not yet developed symptoms. In Vieira’s case, preserved tumor material from his father, who died of prostate cancer in the 1990s, was later found to carry the same RET mutation. The finding suggested that the hereditary alteration had passed silently through the family before being recognized in Vieira.
Researchers say medullary thyroid carcinoma illustrates both the promise and the limitations of precision medicine. Early identification of RET carriers can turn a potentially lethal inherited cancer into a preventable condition, but access to high-quality molecular testing remains uneven. False-negative results can delay life-saving decisions, especially when testing is performed outside specialized centers or when older analytical methods are used. The Brazilian BRASMEN consortium, involving institutions including the University of São Paulo, the Federal University of São Paulo, and the State University of Campinas, is working to improve research and clinical management. For Vieira, broader access to accurate genetic testing could help other families replace years of uncertainty with the possibility of timely prevention.
Subject of Research: Hereditary medullary thyroid carcinoma, RET gene mutations, genetic testing, and preventive cancer surgery
Article Title: Medullary thyroid carcinoma and RET molecular testing: A virtual tumor board on clinical decision-making
Web References: https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.70086 ; https://bv.fapesp.br/en/pesquisador/665140/ana-amelia-fialho-de-oliveira-hoff ; https://bv.fapesp.br/en/pesquisador/79510/lucas-leite-cunha ; https://bv.fapesp.br/en/auxilios/109768
References: DOI: 10.3322/caac.70086
Image Credits: Marcos Vieira
Keywords: medullary thyroid carcinoma, RET gene, hereditary cancer, genetic testing, precision oncology, prophylactic thyroidectomy, cancer prevention, molecular medicine, thyroid cancer, Brazil
