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Hereditary medullary thyroid carcinoma: the management dilemma

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Abstract

Hereditary medullary thyroid carcinoma (hereditary MTC) is a rare malignancy, accounting for 25–30% of all MTC. It occurs as part of multiple endocrine neoplasia type 2 (MEN 2). Autosomal dominant gain-of-function mutations in the RET proto-oncogene is the cause of the disease, in which the common mutations are codons 609, 611, 618, 620, 630, 634 and 918. In recent years, the spectrum of RET gene mutations has changed. The classical mutations reduced, whereas the less aggressive mutations increased. Hereditary MTC is a time-dependent disease. Stages of the disorder at diagnosis can significantly influence survival rates. Based on the genotype–phenotype, RET mutations have been classified into four risk levels by American Thyroid Association (ATA) at 2009. The classification system guides the hereditary MTC management, including risk assessment, biochemical screenings and surgical intervention. Though the application of genetic testing and codon-specific phenotypes in hereditary MTC diagnosis is effective with high accuracy, there are some difficulties in implementing RET gene testing as a routine for MTC diagnosis. And most of carriers with RET mutations did not undergo thyroidectomy at the age recommended by the ATA guidelines. The aim of the study is to review the hereditary MTC and discuss the management dilemma.

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Abbreviations

RET:

Rearranged during transfection

Hereditary MTC:

Hereditary medullary thyroid carcinoma

MEN 2:

Multiple endocrine neoplasia type 2

ATA:

American Thyroid Association

MTC:

Medullary thyroid carcinoma

CCH:

C-cell hyperplasia

Pheo:

Pheochromocytoma

HPT:

Hyperparathyroidism

FMTC:

Familial MTC

VUS:

Variant of unknown significance

HSCR:

Hirschsprung disease

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Acknowledgments

We are deeply appreciative of our mentors and friends for guide and help, including Zhi-Min Ma, Wen-He Zhao, Wei-Bing Wang and Xin-Xing Duan. And we thank the following institutions which provided valuable information: Department of Surgical oncology and Pathology of the first affiliated hospital of Zhejiang university school of medicine.

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There are no conflicts of interest.

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Authors and Affiliations

  1. Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China

    Ping Zhou, Bing Wang & Rong Yang

  2. Trauma Center, The Affiliated Hospital of Hainan Medical College, 31 Long Hua Road, Haikou, 571100, China

    Shao-Wen Cheng

  3. Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China

    Ling Peng

  4. Department of Surgical Oncology, Hangzhou Hospital of Traditional Chinese Medicine, 453 Stadium Road, Hangzhou, 310007, Zhejiang Province, China

    Jian Liu

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  1. Ping Zhou
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Correspondence to Jian Liu.

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Ping Zhou and Jian Liu contributed equally to this work.

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Zhou, P., Liu, J., Cheng, SW. et al. Hereditary medullary thyroid carcinoma: the management dilemma. Familial Cancer 11, 157–165 (2012). https://doi.org/10.1007/s10689-011-9501-7

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