Medullary Thyroid Carcinoma: Screening the Family of the Apparently Sporadic Case

The article presents results of diagnostics, surgical treatment and follow-up of patients with rare hereditary-conditioned forms of thyroid cancer – medullary thyroid carcinoma in content of multiple endocrine neoplasia syndrome. Particular attention is paid to the examination and tactics of treatment of children and adolescents with family genetically confirmed Sipple syndrome. The disease is diagnosed in 4 families. Syndrome of multiple endocrine neoplasia 2a type we found in 7 (0.024%) of 29,325 children and adult patients. All the children were from families in which one of the blood relatives suffered medullary thyroid cancer. The family nature of the disease was confirmed by molecular genetic studies that revealed mutations in C634 (T1900C) in the 11 exon of the RET gene. Only in 3 out of 7 cases thyroidectomy was prophylactic. Four children were fond foci of medullary carcinoma in the removed thyroid gland. In total, 22 operations were performed for the members of 4 families suffering from the family syndrome MEN-2a. The article shows that if a patient is diagnosed Sippl's syndrome, all his blood relatives need to be checked for the mutation of the RET gene to identify familial medullary thyroid cancer, adenomas of parathyroid glands and pheochromocytomas. Early removal of the thyroid gland (in children under the age of 5 years) prevents medullary cancer, and timely diagnosis and adequate surgical removal of neoplasms of parathyroid glands and adrenal glands ensure recovery of the patients. Closest relatives should be checked for the level of calcium and calcitonin, catecholamines, vanillylmandelic acid and metanephrine, ACTH, cancer-embryonic antigen.

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All in the family? Analyzing the impact of family history in addition to genotype on medullary thyroid carcinoma aggressiveness in MEN2A patients

Familial Cancer ◽

10.1007/s10689-016-9948-7 ◽

2016 ◽

Vol 16 (2) ◽

pp. 283-289 ◽

Cited By ~ 7

Author(s):

Kristin L. Long ◽

Carol Etzel ◽

Thereasa Rich ◽

Samuel Hyde ◽

Nancy D. Perrier ◽

...

Keyword(s):

Family History ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Medullary Thyroid ◽

The Family ◽

The Impact

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RET oncogene mutations in a large Korean kindred with familial medullary thyroid carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6066 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6066-6066

Author(s):

Y. Lee ◽

H. Park ◽

J. Jung ◽

Y. Lim ◽

S. Uchino

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Germ Line ◽

Radical Neck Dissection ◽

Gene Mutations ◽

Large Family ◽

Carrier Status ◽

Medullary Thyroid ◽

Familial Medullary Thyroid Carcinoma ◽

The Family

6066 Background: Familial medullary thyroid carcinoma (FMTC) is related to germ-line mutations in the RET proto-oncogene. The mutations concern mainly cystein residues in exons 10 and 11, whereas noncystein mutations in exons 13–16 are rare. These mutations have been recorded in the different populations, but to date there is no corresponding study in Korean families. In this study, we identify the RET mutations in the Korean family with FMTC and propose therapeutic approach in managing the disorder. Methods: The large family consists of 4 generations with a total of 32 individuals. There was a history of MTC in five members of the family. The index case was a 67-yr- old woman who underwent total thyroidectomy and both modified radical neck dissection in our hospital at the age of 48. We analysed exons 10, 11, 13, 14, 15 and 16 in index patients using DNA sequencing. Twenty-nine subjects from the family were clinically assessed and subsequently molecularly analysed for the presence of RET gene mutations. Results: We have found a missense TGC?AGC mutation at codon 618 in Exon 10. This transversion leads to the substitution of cystein with serin. The mutation was detected in all five MTC patients as well as in 6 asymptomatic relatives. The mutation shows a wide clinical heterogenecity, as there are carrier patients with age of diagnosis ranging from 9 to 64 years. Conclusions: It is likely that the mutation causes FMTC, because no other mutation was found in RET. This study showed 100% accordance between presence of the disease and gene carrier status is reported. Total preventive thyroidectomy has been recommended in all carriers of RET genetic defects. No significant financial relationships to disclose.

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Comparison Between Clinicopathological Characteristics, BRAF V600E and TERT Promoter Mutation of Familial Non-Medullary Thyroid Carcinomas, and Sporadic Case

Frontiers in Oncology ◽

10.3389/fonc.2021.616974 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tian Yang ◽

Longsheng Huang ◽

Chang Chen ◽

Han Luo ◽

Yong Jiang

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Nodular Goiter ◽

Sporadic Case ◽

Clinicopathological Characteristics ◽

Braf V600e ◽

Biological Behavior ◽

Promoter Mutation ◽

Medullary Thyroid ◽

Significant Difference

BackgroundIt has been debated whether familial non-medullary thyroid carcinoma (FNMTC) is more aggressive and has a worse prognosis than sporadic non-medullary thyroid carcinoma (SNMTC). Our aim was to compare the invasiveness and prognosis of FNMTC and SNMTC by their biological behavior and molecular changes.Method and MaterialOur group mainly compared 106 patients with FNMTC whom have complete clinicopathological data during 2011–2019 in West China Hospital, Sichuan University, and 212 randomly selected cases with SNMTC were included to compare their biological behavior, recurrence and mortality, and molecular expression of BRAF V600E and TERT promoter. At the same time, FNMTC cases were divided into four subgroups, namely, two affected members group, three or more affected members, parent/offspring group, and sibling group, and they were compared with SNMTC separately to analyze the difference in their invasiveness and prognosis.ResultsWe found that the mean tumor size of FNMTC (0.96 ± 0.53cm) was smaller than that of SNMTC (1.15 ± 0.72 cm) (p = 0.020), while no significant difference in the incidence of other clinicopathological factors, including bilateral growth, capsular invasion, with thyroid nodular goiter or not, multifocality, lymph node metastasis, extrathyroidal extension, iodine 131 treatments, T stage, and American Joint Committee on Cancer (AJCC) stage, was observed between FNMTC and SNMTC (p > 0.05), between each FNMTC subgroup (p > 0.05), and between each FNMTC subgroup and SNMTC (p > 0.05). There was no significant difference in recurrence, mortality, and BRAF V600E and TERT promoter mutation between FNMTC and SNMTC, among which 50/60 (83.33%) of FNMTC patients had BRAF V600E mutation and 1/32 (3.13%) had TERT promoter mutation, while the mutation rates of SNMTC were 93/108 (86.11%) and 3/64 (4.69%) (p > 0.05).ConclusionThere was no significant difference in invasiveness and prognosis between FNMTC and SNMTC by biological behavior, patient survival, and molecular level comparison.

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