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

2016 ◽  
Vol 16 (2) ◽  
pp. 283-289 ◽  
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

scholarly journals Results and Clinical Interpretation of Germline RET Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3268
Author(s):  
Giovanni Innella ◽  
Cesare Rossi ◽  
Maria Romagnoli ◽  
Andrea Repaci ◽  
Davide Bianchi ◽  
...  
Keyword(s):  
Family History ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Cancer Genetics ◽  
Positive Family History ◽  
Risk Class ◽  
Medullary Thyroid ◽  
Risk Variants ◽  
Uncertain Significance ◽  
The Difference

Germline RET variants are responsible for approximately 25% of medullary thyroid carcinoma (MTC) cases. Identification of RET variant carriers allows for the adoption of preventative measures which are dependent on the risk associated with the specific alteration. From 2002 to 2020, at our cancer genetics clinic, RET genetic testing was performed in 163 subjects (102 complete gene analyses and 61 targeted analyses), 72 of whom presented with MTC. A germline RET variant was identified in 31.9% of patients affected by MTC (93.8% of those having positive family history and 14.3% of clinically sporadic cases). Subsequent target testing in relatives allowed us to identify 22 asymptomatic carriers, who could undertake appropriate screening. Overall, patients with germline RET variants differed significantly from those who tested negative by family history (p < 0.001) and mean age at MTC diagnosis (44.45 vs. 56.42 years; p = 0.010), but the difference was not significant when only carriers of moderate risk variants were considered (51.78 vs. 56.42 years; p = 0.281). Out of 12 different variants detected in 49 patients, five (41.7%) were of uncertain significance (VUS). For two of these, p.Ser904Phe and p.Asp631_Leu633delinsGlu, co-segregation and genotype/phenotype analysis, matched with data from the literature, provided evidence supporting their classification in the moderate and the highest/high risk class (with a MEN2B phenotype), respectively.

Prophylactic thyroidectomy as method of medullary thyroid carcinoma prevention in children from MEN syndrom families

2017 ◽  
Vol 8 (5) ◽  
pp. 5-11
Author(s):  
Zoya S. Matveeva ◽  
Anatoliy F. Romanchishen ◽  
Alexandr V. Gostimsky ◽  
Kristina V. Vabalayte
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Gland ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Multiple Endocrine Neoplasia ◽  
Medullary Thyroid Cancer ◽  
Parathyroid Glands ◽  
Medullary Thyroid ◽  
Endocrine Neoplasia ◽  
The Family

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.

Medullary Thyroid Carcinoma in Multiple Endocrine Neoplasm Type II Syndromes

1985 ◽  
Vol 71 (4) ◽  
pp. 397-401 ◽  
Author(s):  
A.S. Fassina ◽  
A. Scapinello ◽  
M.R. Pelizzo ◽  
P. Dall'Orto ◽  
G. Viale ◽  
...  
Keyword(s):  
Family History ◽  
Thyroid Gland ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Positive Family History ◽  
Biological Behavior ◽  
Type Ii ◽  
Cell Hyperplasia ◽  
Medullary Thyroid ◽  
C Cell Hyperplasia

A case of multiple endocrine neoplasm (MEN) type IIa and 2 cases of MEN type IIb are reported. The biological behavior of medullary thyroid carcinoma was more aggressive in the MEN type IIb. C-cell hyperplasia was present in the thyroid gland of the patient with a positive family history.

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

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.

Combined treatment and survival of medullary thyroid carcinoma patients

Open Medicine ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. 426-430
Author(s):  
Zenonas Baranauskas ◽  
Konstantinas Valuckas ◽  
Giedre Smailyte
Keyword(s):  
Prognostic Factors ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
External Beam Radiotherapy ◽  
Combined Treatment ◽  
Term Survival ◽  
Long Term Survival ◽  
Medullary Thyroid ◽  
The Impact

AbstractThe aim of this study is to analyze the impact of combined treatment (thyroidectomy and radiotherapy and radioactive iodine treatment) on patients’ long-term survival with medullary thyroid carcinoma. This is a retrospective study of 59 patients treated from 1977 to 2006 for medullary carcinoma at the Institute of Oncology in Vilnius, Lithuania. Survival was estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were used to explore the association of prognostic factors with long-term survival. The survival of MTC patients was 88.0% (95% CI 68.0–88.9), 67.9% (95% CI 52.3–79.4) and 60.5% (95% CI 43.2–74.0), respectively, 5, 10 and 15 years after diagnosis. In survival analysis, only the type of surgery and lymph node involvement were found to be significant prognostic factors. The results of this study suggest that treatment with radioiodine and external beam radiotherapy do not improve significantly the long-term survival of surgically treated MTC patients.

scholarly journals Familial Non-Medullary Thyroid Carcinoma in Pediatric Age: Our Surgical Experience

2021 ◽  
Author(s):  
Claudio Spinelli ◽  
Irene Piccolotti ◽  
Alessia Bertocchini ◽  
Riccardo Morganti ◽  
Gabriele Materazzi ◽  
...  
Keyword(s):  
Family History ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Statistical Significance ◽  
Positive Family History ◽  
Biological Behavior ◽  
Medullary Thyroid ◽  
Operative Evaluation ◽  
Nosological Entity ◽  
The University

Abstract Background The purpose of the article was to evaluate the existence of significant clinical, pathological and prognostic differences between familial and sporadic form of pediatric non-medullary thyroid carcinoma, in order to tailor the therapeutic strategy to be adopted for patients with family history. Methods We analyzed the records of 76 pediatric patients that underwent surgery for differentiated thyroid cancer from 2014 to 2019 at the Surgical Pathology Department of the University of Pisa, Italy. Among these, 20 (26,3%) had positive family history (familial non-medullary thyroid carcinoma—FNMTC group) while 56 (73.7%) were affected by sporadic forms (sporadic non-medullary thyroid carcinoma—SNMTC group). Results In our study, the correlation between the FNMTC and the SNMTC group showed no difference in terms of tumor features like multifocality, bilaterality, capsular/extracapsular invasion and the presence of vascular emboli. A statistical significance, on the other hand, was revealed by observation of clinical outcomes, such as distant metastasis (p = 0,022), persistence of disease (p = 0,054) and necessity of radioiodine sessions (p = 0,005). Conclusions These findings suggest that family history may have an independent role on the outcome, expressing its action through an intrinsic more aggressive biological behavior. Therefore, familial non-medullary thyroid carcinoma in children represents a nosological entity that requires an accurate pre-operative evaluation, an adequate surgical strategy and a careful follow up.

scholarly journals Chemoembolization for Liver Metastases from Medullary Thyroid Carcinoma

2006 ◽  
Vol 91 (7) ◽  
pp. 2496-2499 ◽  
Author(s):  
J. Fromigué ◽  
T. De Baere ◽  
E. Baudin ◽  
C. Dromain ◽  
S. Leboulleux ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Liver Metastases ◽  
Medullary Thyroid Carcinoma ◽  
Median Duration ◽  
Early Stage ◽  
Somatostatin Analogs ◽  
Evaluation Criteria ◽  
Distant Metastases ◽  
Medullary Thyroid ◽  
The Impact

Abstract Background: Medullary thyroid carcinoma (MTC) is a well-differentiated neuroendocrine tumor. Distant metastases are the main cause of cancer-related death. Systemic chemotherapy produces only rare tumor responses. Somatostatin analogs and other available modalities are poorly effective to control symptoms. Aims: The aim of our study was to evaluate the impact of liver transarterial chemoembolization (TACE) in MTC patients with predominant and progressive liver metastases. Patients and Methods: Twelve MTC patients underwent 18 TACE courses (mean, 1.5; range, 1–2). Response evaluation criteria in solid tumors were used to evaluate tumor responses. Symptomatic responses were defined by more than a 25% decrease of symptoms intensity. Results: Partial radiological tumor response was obtained in five patients (42%) with a median duration of 17 months (mean, 19; range, 15–28 months), stabilization in five (42%) with a median duration of 24 months (mean, 24; range, 4–39 months), and progression in the remaining two (16%). The five partial tumor responses were observed in the nine patients with less than 30% liver involvement. Clinical response was observed in two of the five patients with diarrhea. Carcinoembryonic antigen did not appear to be a useful marker in this setting. Significant grade 3–4 toxicity was observed in one patient who had a major tumor necrosis after TACE. Conclusion: TACE should be considered for treating MTC patients with progressive and predominant liver metastasis, and preferably at an early stage during the course of metastatic disease.

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