Clinic Heterogeneity and Management of Pediatric Patients With Germline RET Proto-oncogene Mutation: Single-center Experience.
Journal
Journal of pediatric hematology/oncology
ISSN: 1536-3678
Titre abrégé: J Pediatr Hematol Oncol
Pays: United States
ID NLM: 9505928
Informations de publication
Date de publication:
01 10 2023
01 10 2023
Historique:
received:
12
01
2022
accepted:
02
06
2023
medline:
28
9
2023
pubmed:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
Inherited forms of medullary thyroid carcinoma (MTC) can cause serious problems in diagnosis and follow-up. Family screening is performed, and prophylactic thyroidectomy at an appropriate age can be life-saving. This study aimed to investigate the diagnostic, clinical, laboratory characteristics, and treatment methods of cases with rearranged during transfection ( RET) mutation in the childhood age group. Patients diagnosed with hereditary MTC and patients who were evaluated by detecting MTC and/or RET mutations in their families were included in this study. Nine cases from 6 families were included in the study. Seven patients were evaluated as a result of screening, whereas 2 patients, one of whom was MEN2B, were symptomatic. Prophylactic thyroidectomy was performed in 7 cases. Medullary microcarcinoma was found in all, and additional papillary thyroid carcinoma in one. An inoperable tumor was detected in one patient, and sorafenib treatment was applied. A very heterogeneous clinical presentation can be seen in a group of pediatric patients with RET mutation. In rare RET mutations, the genotype-phenotype relationship is still unclear, and different clinical pictures can be seen. Although prophylactic thyroidectomy is life-saving, it can cause iatrogenic hypothyroidism and hypoparathyroidism. Concomitant papillary microcarcinomas may occur in very young children with germline RET mutation.
Identifiants
pubmed: 37526376
doi: 10.1097/MPH.0000000000002728
pii: 00043426-990000000-00269
doi:
Substances chimiques
Proto-Oncogene Proteins c-ret
EC 2.7.10.1
RET protein, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e789-e797Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Parkhurst E, Calonico E, Abboy S. Utilization of genetic testing for RET mutations in patients with medullary thyroid carcinoma: a single-center experience. J Genet Couns. 2018;27:1411–1416.
Opsahl EM, Brauckhoff M, Schlichting E, et al. A nationwide study of multiple endocrine neoplasia type 2A in Norway: predictive and prognostic factors for the clinical course of medullary thyroid carcinoma. Thyroid. 2016;26:1225–1238.
İnce D, Demirağ B, Ataseven E, et al. Child with RET proto-oncogene codon 634 mutation. Turk J Pediatr. 2017;59:590–593.
Wells SA Jr, Asa SL, Dralle H, et al. American Thyroid Association Guidelines task force on medullary thyroid carcinoma. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25:567–610.
Kuhlen M, Frühwald MC, Dunstheimer DPA, et al. Revisiting the genotype-phenotype correlation in children with medullary thyroid carcinoma: a report from the GPOH-MET registry. Pediatr Blood Cancer. 2020;67:e28171.
Qi XP, Zhao JQ, Fang XD, et al. Spectrum of germline RET variants identified by targeted sequencing and associated multiple endocrine neoplasia type 2 susceptibility in China. BMC Cancer. 2021;21:369.
Febrero B, Rodríguez JM, Ríos A, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia 2 (MEN2) patients with the C634Y mutation: a long-term follow-up in a large single-center cohort. Eur J Surg Oncol. 2019;45:625–630.
Machens A, Dralle H. Familial prevalence and age of RET germline mutations: implications for screening. Clin Endocrinol (Oxf). 2008;69:81–87.
Aydoğan Bİ, Yüksel B, Tuna MM, et al. Distribution of RET mutations and evaluation of treatment approaches in hereditary medullary thyroid carcinoma in Turkey. J Clin Res Pediatr Endocrinol. 2016;8:13–20.
Schulte KM, Machens A, Fugazzola L, et al. The clinical spectrum of multiple endocrine neoplasia type 2a caused by the rare intracellular RET mutation S891A. J Clin Endocrinol Metab. 2010;95:E92–E97.
Qi XP, Zhao JQ, Chen ZG, et al. RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D. Oncotarget. 2015;6:33993–34003.
Bim LV, Navarro FCP, Valente FOF, et al. Retroposed copies of RET gene: a somatically acquired event in medullary thyroid carcinoma. BMC Med Genomics. 2019;12:104.
Tanaka A, Uemura H, Morimoto C, et al. Four cases of medullary thyroid carcinomas associated with multiple endocrine neoplasia 2B with rearranged during transfection codon M918T mutation in the same family. Mol Clin Oncol. 2022;16:13.
Machens A, Dralle H. Biological relevance of medullary thyroid microcarcinoma. J Clin Endocrinol Metab. 2012;97:1547–1553.
Tang PY, Khor LY, Takano A. Synchronous papillary thyroid carcinoma and medullary thyroid carcinoma—a pitfall waiting to happen. Malays J Pathol. 2017;39:171–174.
Nangue C, Bron L, Portmann L, et al. Mixed medullary-papillary carcinoma of the thyroid: report of a case and review of the literature. Head Neck. 2009;31:968–974.
Kim WG, Gong G, Kim EY, et al. Concurrent occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma in the same thyroid should be considered as coincidental. Clin Endocrinol (Oxf). 2010;72:256–263.
Dionigi G, Castano P, Bertolini V, et al. Simultaneous medullary and papillary thyroid cancer: two case reports. J Med Case Rep. 2007;1:133.
Cracolici V, Mujacic I, Kadri S, et al. Synchronous and metastatic papillary and follicular thyroid carcinomas with unique molecular signatures. Endocr Pathol. 2018;29:9–14.
Adnan Z, Arad E, Dana J, et al. Simultaneous occurrence of medullary and papillary thyroid microcarcinomas: a case series and review of the literature. J Med Case Rep. 2013;7:26.
Abdelaal A, El Ansari W, Abusabeib A, et al. Simultaneous occurrence of follicular and papillary thyroid carcinomas in same thyroid lobe: a case series of six patients from Qatar. Int J Surg Case Rep. 2020;73:65–70.
Chambers M, Tafe LJ, Gutmann EJ, et al. Cytologic features of a case of mixed medullary and follicular cell-derived thyroid carcinoma with review of the literature. Diagn Cytopathol. 2021;49:E125–E129.
Shah K, Zena M, Adickes ED, et al. Case of concurrent MTC and PTC in a patient with a germline RET mutation. Endocr Pathol. 2015;26:279–283.
Fibbi B, Pinzani P, Salvianti F, et al. Synchronous occurrence of medullary and papillary carcinoma of the thyroid in a patient with cutaneous melanoma: determination of BRAFV600E in peripheral blood and tissues. Report of a case and review of the literature. Endocr Pathol. 2014;25:324–331.
Goyal R, Nada R, Rao KL, et al. Mixed medullary and follicular cell carcinoma of the thyroid with lymph node metastasis in a 7-year-old child. Pathol Int. 2006;56:84–88.
Ilanchezhian M, Khan S, Okafor C, et al. Update on the treatment of medullary thyroid carcinoma in patients with multiple endocrine neoplasia type 2. Horm Metab Res. 2020;52:588–597.
Kocsis J, Szekanecz É, Bassam A, et al. First line sorafenib treatment for metastatic medullary thyroid cancer: efficacy and safety analysis. Exp Clin Endocrinol Diabetes. 2019;127:240–246.
de Castroneves LA, Negrão MV, de Freitas RM, et al. Sorafenib for the treatment of progressive metastatic medullary thyroid cancer: efficacy and safety analysis. Thyroid. 2016;26:414–419.
Wells SA Jr. Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors. Endocr Relat Cancer. 2018;25:T1–T13.