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Controversy on the management of patients carrying RET p.V804M mutation

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Abstract

Context

RET p.V804M is classified as a moderate risk mutation for familial medullary thyroid cancer (FMTC). There is a significant controversy on the management of patients carrying this mutation. We describe a family incidentally discovered to have this mutation and review the literature on RET p.V804M mutation.

Results

The proband was born to first-degree relative parents. He was noticed to have hypertrophy of some parts of the body and vascular skin changes. Whole-exome sequencing of DNA extracted from a skin biopsy showed a mutation in the PIK3CA (c.3132T>G, p.ASN1044LYS). This variant was not found in DNA extracted from blood. This confirmed the diagnosis of CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi and Scoliosis, skeletal or spinal anomalies). Another incidentally found mutation in the skin biopsy and blood sample was RET p.V804M. Although there was no family history of MTC or MEN 2 syndromes, family screening revealed RET p.V804M mutation and FMTC in the proband’s father, paternal grandmother, one sister, and one aunt. There was significant interfamilial heterogeneity in the age of presentation and pathology. A review of literature showed that RET p.V804M mutation is a moderate risk mutation associated with late-onset FMTC, usually at middle to old age.

Conclusion

Despite the controversy and the heterogeneous presentation of patients with RET p.V804M mutation, our study and review of the literature suggest that this seemingly “low” risk mutation is associated with late-onset but potentially aggressive MTC. This indicates the need for follow-up and timely intervention based on calcitonin level elevation.

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Acknowledgements

The authors would like to thank the family members who agreed to participate in this study and the staff of the Molecular Endocrine Section, Department of Molecular Oncology

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Authors and Affiliations

  1. Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Ali S. Alzahrani, Meshael Alswailem & Balgees Alghamdi

  2. Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Ali S. Alzahrani

  3. Center of Genomic Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Rafiullah Rafiullah

  4. Endocrinology & Diabetes Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia

    Mohammed Aldawish

  5. Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Hindi Al-Hindi

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  1. Ali S. Alzahrani
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Correspondence to Ali S. Alzahrani.

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Alzahrani, A.S., Alswailem, M., Alghamdi, B. et al. Controversy on the management of patients carrying RET p.V804M mutation. Endocrine 75, 478–486 (2022). https://doi.org/10.1007/s12020-021-02895-8

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