Surgical and clinical strategies in the management of thyroid medullary carcinoma in children with and without ret proto- oncogene mutations

Boybeyi-Türer Ö, Vurallı D, Karnak İ, Gönç N, Yalçın EŞ, Orhan D, Kandemir N, Tanyel FC. Surgical and clinical strategies in the management of thyroid medullary carcinoma in children with and without ret proto-oncogene mutations. Turk J Pediatr 2016; 58: 436-441.Medullary thyroid carcinoma (MTC) may arise sporadically or in familial manner. We presented sporadic and familial cases with MTC in order to raise awareness on management of such patients. Three medullary thyroid carcinoma (MTC) cases were presented. Case 1 had RET634 mutation; managed with total thyroidectomy (TT) and cervical lymph node dissection (CLND). Case 2 had RET804 mutation; managed with prophylactic TT. Case 3 had thyroid nodule; managed with TT and CLND. Case 1 had micro-carcinomatosis foci, Case 2 had normal thyroid tissue in histopathological examination and Case 3 had medullary thyroid carcinoma with tumor negative surgical borders. Case 1 was re-operated for persisting focus of disease. Follow-up of cases were uneventful. Clinicians and surgeons should be aware of critical timing for surgery and various surgical and clinical strategies in the management of MTC in children.

PDF

___

1. Tavares MR, Toledo SP, Montenegro FL, et al. Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2. Clinics (Sao Paulo) 2012; 67: 149-154.

2. Morris LF, Waguespack SG, Edeiken-Monroe BS, et al. Ultrasonography should not guide the timing of thyroidectomy in pediatric patients diagnosed with multiple endocrine neoplasia syndrome 2A through genetic screening. Ann Surg Oncol 2013; 20: 53-59.

3. Romei C, Pardi E, Cetani F, Elisei R. Genetic and clinical features of multiple endocrine neoplasia types 1 and 2. J Oncol 2012: 705036.

4. Kloos RT, Eng C, Evans DB, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009; 19: 565-612.

5. Wiersinga WM. Thyroid cancer in children and adolescents--consequences in later life. J Pediatr Endocrinol Metab 2001; 14: 1289-1296.

6. Spinelli C, Di Giacomo M, Costanzo S, Elisei R, Miccoli P. Role of RET codonic mutations in the surgical management of medullary thyroid carcinoma in pediatric age multiple endocrine neoplasm type 2 syndromes. J Pediatr Surg 2010; 45: 1610-1616.

7. Pacini F, Castagna MG, Cipri C, Schlumberger M. Medullary thyroid carcinoma. Clin Oncol (R Coll Radiol) 2010; 22: 475-485.

8. Marsh DJ, Learoyd DL, Andrew SD, et al. Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma. Clin Endocrinol (Oxf) 1996; 44: 249-257.

9. Elisei R, Romei C, Cosci B, et al. RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab 2007; 92: 4725-4729.

10. Moline J, Eng C. Multiple endocrine neoplasia type 2: an overview. Genet Med 2011; 13: 755-764.

11. Miyauchi A, Futami H, Hai N, et al. Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation. Jpn J Cancer Res 1999; 90: 1-5.

12. Hansford JR, Mulligan LM. Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis. J Med Genet 2000; 37: 817-827.

13. Donis-Keller H, Dou S, Chi D, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet 1993; 2: 851-856.

14. Mulligan LM, Kwok JB, Healey CS, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993; 363: 458- 460.

15. Jarzab B, Szpak-Ulczok S, Wloch J, Czarniecka A, Krajewska J. Timing and criteria for prophylactic thyroidectomy in asymptomatic RET carriers - the role of Ct serum level. Thyroid Res 2013; 6: S9.

16. Salehian B, Samoa R. RET gene abnormalities and thyroid disease: who should be screened and when. J Clin Res Pediatr Endocrinol 2013; 5: 70-78.

17. Elisei R, Romei C, Renzini G, et al. The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center. J Clin Endocrinol Metab 2012; 97: 426-435.

18. Machens A, Dralle H. Prophylactic thyroidectomy in RET carriers at risk for hereditary medullary thyroid cancer. Thyroid 2009; 19: 551-554.

19. Frank-Raue K, Buhr H, Dralle H, et al. Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype. Eur J Endocrinol 2006; 155: 229-236.

20. Marsh DJ, McDowall D, Hyland VJ, et al. The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families. Clin Endocrinol (Oxf) 1996; 44: 213-220.

21. Machens A, Lorenz K, Dralle H. Individualization of lymph node dissection in RET (rearranged during transfection) carriers at risk for medullary thyroid cancer: value of pretherapeutic calcitonin levels. Ann Surg 2009; 250: 305-310.

22. Schreinemakers JM, Vriens MR, Valk GD, et al. Factors predicting outcome of total thyroidectomy in young patients with multiple endocrine neoplasia type 2: a nationwide long-term follow-up study. World J Surg 2010; 34: 852-860.

23. Niederle B, Sebag F, Brauckhoff M. Timing and extent of thyroid surgery for gene carriers of hereditary C cell disease--a consensus statement of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg 2014; 399: 185-197.

24. Grubbs EG, Waguespack SG, Rich TA, et al. Do the recent American Thyroid Association (ATA) Guidelines accurately guide the timing of prophylactic thyroidectomy in MEN2A? Surgery 2010; 148: 1302- 1309.

25. Cohen R, Campos JM, Salaun C, et al. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d'Etudes des Tumeurs a Calcitonine (GETC). J Clin Endocrinol Metab 2000; 85: 919-922.

26. Watson CG, Felling J, Maceachern DG. Objective Draw-a-Person scales: an attempted cross-validation. J Clin Psychol 1967; 23: 382-386.

27. Jimenez C, Hu MI, Gagel RF. Management of medullary thyroid carcinoma. Endocrinol Metab Clin North Am 2008; 37: 481-496.

28. Skinner MA, Moley JA, Dilley WG, Owzar K, Debenedetti MK, Wells SA, Jr. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 2005; 353: 1105-1113.

29. Rodriguez JM, Balsalobre M, Ponce JL, et al. Pheochromocytoma in MEN 2A syndrome. Study of 54 patients. World J Surg 2008; 32: 2520-2526.

30. Nguyen L, Niccoli-Sire P, Caron P, et al. Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study. Eur J Endocrinol 2001; 144: 37-44.