Diagnosis and treatment of medullary thyroid carcinoma-an update

doi:10.16139/j.1007-9610.2022.03.019

Abstract

Abstract:

Medullary thyroid carcinoma (MTC) arising from the parafollicular cell (C cell) of the thyroid gland, is an aggressive neuroendocrine tumor and a special rare thyroid malignancy. Calcitonin and carcinoembryonic antigen are still commonly used markers now, whose elevation can reliably diagnose MTC. The preoperative value and postoperative doubling time of these markers are of great significance for range of lymph node dissection and evaluation of prognosis. It is recommended that total thyroidectomy and central lymph node dissection would be needed and lateral lymph node dissection would be added when necessary. Routine detection of RET gene is recommended. Targeted therapy is considered for non-operable patients or the patients with distant metastasis. The pathological mechanism of MTC still needs to be paid attention.

Key words: Medullary thyroid carcinoma, Calcitonin, Surgical treatment

CLC Number:

R736.1

CHEN Chengkun, GUO Bomin, DENG Xianzhao, WU Bo, FAN Youben. Diagnosis and treatment of medullary thyroid carcinoma-an update[J]. Journal of Surgery Concepts & Practice, 2022, 27(03): 276-280.

Figures/Tables 1

References 35

[1]	Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma[J]. Thyroid, 2015, 25(6):567-610. doi: 10.1089/thy.2014.0335 URL
[2]	Mathiesen JS, Kroustrup JP, Vestergaard P, et al. Incidence and prevalence of sporadic and hereditary MTC in Denmark 1960-2014: a nationwide study[J]. Endocr Connect, 2018, 7(6):829-839. doi: 10.1530/EC-18-0157 pmid: 29760189
[3]	Torresan F, Mian C, Cavedon E, et al. Cure and survival of sporadic medullary thyroid carcinoma following systematic preoperative calcitonin screening[J]. Langenbecks Arch Surg, 2019, 404(4):411-419. doi: 10.1007/s00423-019-01764-3 URL
[4]	Kihara M, Miyauchi A, Kudo T, et al. Serum calcitonin reference values for calcium stimulation tests by electrochemiluminescence immunoassay in Japanese men with non-medullary thyroid carcinoma[J]. Surg Today, 2018, 48(2):223-228. doi: 10.1007/s00595-017-1578-7 URL
[5]	Giovanella L, Imperiali M, Piccardo A, et al. Procalcitonin measurement to screen medullary thyroid carcinoma: a prospective evaluation in a series of 2 705 patients with thyroid nodules[J]. Eur J Clin Invest, 2018, 48(6):e12934. doi: 10.1111/eci.12934 URL
[6]	Parmer M, Milan S, Torabi A. Calcitonin-negative neuroendocrine tumor of the thyroid[J]. Int J Surg Pathol, 2017, 25(2):191-194. doi: 10.1177/1066896916670989 pmid: 27658647
[7]	Liang X, Zhu J, Cai M, et al. Progrp as a novel biomar-ker for the differential diagnosis of medullary thyroid carcinoma in patients with thyroid nodules[J]. Endocr Pract, 2020, 26(5):514-522. doi: 10.4158/EP-2019-0396 URL
[8]	Turkdogan S, Forest VI, Hier MP, et al. Carcinoembryo-nic antigen levels correlated with advanced disease in medullary thyroid cancer[J]. J Otolaryngol Head Neck Surg, 2018, 47(1):55. doi: 10.1186/s40463-018-0303-x pmid: 30223887
[9]	Parra-Robert M, Orois A, Augé JM, et al. Utility of proGRP as a tumor marker in the medullary thyroid carcinoma[J]. Clin Chem Lab Med, 2017, 55(3):441-446. doi: 10.1515/cclm-2016-0572 pmid: 27754959
[10]	Maleki Z, Abram M, Dell′Aquila M, et al. Insulinoma-associated protein 1 (INSM-1) expression in medullary thy-roid carcinoma FNA: a multi-institutional study[J]. J Am Soc Cytopathol, 2020, 9(3):185-190. doi: S2213-2945(20)30032-6 pmid: 32197966
[11]	Suzuki A, Hirokawa M, Takada N, et al. Fine-needle aspiration cytology for medullary thyroid carcinoma: a single institutional experience in Japan[J]. Endocr J, 2017, 64(11):1099-1104. doi: 10.1507/endocrj.EJ17-0238 pmid: 28883261
[12]	Liu MJ, Liu ZF, Hou YY, et al. Ultrasonographic characteristics of medullary thyroid carcinoma: a comparison with papillary thyroid carcinoma[J]. Oncotarget, 2017, 8(16):27520-27528. doi: 10.18632/oncotarget.15897 URL
[13]	Wang L, Kou H, Chen W, et al. The diagnostic value of ultrasound in medullary thyroid carcinoma: a comparison with computed tomography[J]. Technol Cancer Res Treat, 2020, 19:1533033820905832.
[14]	Kushchayev SV, Kushchayeva YS, Tella SH, et al. Medullary thyroid carcinoma: an update on imaging[J]. J Thyroid Res, 2019, 2019:1893047.
[15]	Yamaga LYI, Cunha ML, Campos Neto GC, et al. ⁶⁸Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion comparison with ¹¹¹In-octreotide SPECT/CT and conventional imaging[J]. Eur J Nucl Med Mol Imaging, 2017, 44(10):1695-1701. doi: 10.1007/s00259-017-3701-9 URL
[16]	Giovanella L, Treglia G, Iakovou I, et al. EANM practice guideline for PET/CT imaging in medullary thyroid carcinoma[J]. Eur J Nucl Med Mol Imaging, 2020, 47(1):61-77. doi: 10.1007/s00259-019-04458-6 URL
[17]	Zhang X, Yan D, Wang J, et al. Is new American Thyroid Association risk classification for hereditary medullary thyroid carcinoma applicable to Chinese patients? a single-center study[J]. Chin J Cancer Res, 2017, 29(3):223-230. doi: 10.21147/j.issn.1000-9604.2017.03.08 URL
[18]	Elisei R, Bottici V, Cappagli V, et al. Clinical utility of genetic diagnosis for sporadic and hereditary medullary thyroid carcinoma[J]. Ann Endocrinol (Paris), 2019, 80(3):187-190. doi: 10.1016/j.ando.2019.04.014 URL
[19]	Kihara M, Miyauchi A, Yoshioka K, et al. Germline RET mutation carriers in Japanese patients with apparently sporadic medullary thyroid carcinoma: a single institution experience[J]. Auris Nasus Larynx, 2016, 43(5):551-555. doi: 10.1016/j.anl.2015.12.016 URL
[20]	Mathiesen JS, Kroustrup JP, Vestergaard P, et al. Completeness of RET testing in patients with medullary thyroid carcinoma in Denmark 1997-2013: a nationwide study[J]. Clin Epidemiol, 2019, 11:93-99. doi: 10.2147/CLEP.S183268 pmid: 30666164
[21]	Essig GF Jr, Porter K, Schneider D, et al. Multifocality in sporadic medullary thyroid carcinoma: an international multicenter study[J]. Thyroid, 2016, 26(11):1563-1572. doi: 10.1089/thy.2016.0255 URL
[22]	de Crea C, Raffaelli M, Milano V, et al. Intraoperative high-dose calcium stimulation test in patients with sporadic medullary thyroid carcinoma is highly accurate in predicting lateral neck metastases[J]. Surgery, 2016, 159(1):70-76. doi: 10.1016/j.surg.2015.08.022 URL
[23]	Filimon S, Payne RJ, Black MJ, et al. Calcitonin secretory index and unsuspected nodal disease in medullary thyroid carcinoma[J]. Endocr Pract, 2018, 24(5):460-467. doi: 10.4158/EP-2017-0236 pmid: 29847167
[24]	Fan W, Xiao C, Wu F. Analysis of risk factors for cervical lymph node metastases in patients with sporadic medullary thyroid carcinoma[J]. J Int Med Res, 2018, 46(5):1982-1989. doi: 10.1177/0300060518762684 URL
[25]	Ye L, Zhou X, Lu J, et al. Combining serum calcitonin, carcinoembryonic antigen, and neuron-specific enolase to predict lateral lymph node metastasis in medullary thyroid carcinoma[J]. J Clin Lab Anal, 2020, 34(7):e23278.
[26]	Wang S, Wang B, Xie C, et al. RET Proto-oncogene gene mutation is related to cervical lymph node metastasis in medullary thyroid carcinoma[J]. Endocr Pathol, 2019, 30(4):297-304. doi: 10.1007/s12022-019-09588-z URL
[27]	史亚飞, 张颖超, 樊友本, 等. 甲状腺髓样癌手术切除范围的研究[J]. 中华普通外科杂志, 2020, 35(11):856-861.
[28]	Werner RA, Schmid JS, Higuchi T, et al. Predictive va-lue of ¹⁸F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib[J]. J Nucl Med, 2018, 59(5):756-761. doi: 10.2967/jnumed.117.199778 URL
[29]	Kocsis J, Szekanecz É, Bassam A, et al. First line sorafenib treatment for metastatic medullary thyroid cancer: efficacy and safety analysis[J]. Exp Clin Endocrinol Diabetes, 2019, 127(4):240-246. doi: 10.1055/s-0044-100378 URL
[30]	Drilon AE, Subbiah V, Oxnard GR, et al. A phase 1 study of LOXO-292, a potent and highly selective RET inhibitor, in patients with RET-altered cancers[J]. J Clin Oncol, 2018, 36:102.
[31]	Gainor JF, Lee DH, Curigliano G, et al. Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients(pts) with advanced RET-fusion+ non-small cell lung cancer(NSCLC)[J]. J Clin Oncol, 2019, 37:9008. doi: 10.1200/JCO.2019.37.15_suppl.9008 URL
[32]	Meng K, Luo H, Chen H, et al. Prognostic value of numbers of metastatic lymph node in medullary thyroid car-cinoma: a population-based study using the SEER 18 database[J]. Medicine (Baltimore), 2019, 98(1):e13884. doi: 10.1097/MD.0000000000013884 URL
[33]	Hassan A, Siddique M, Riaz S, et al. Medullary thyroid carcinoma: prognostic variables and tumour markers affecting survival[J]. J Ayub Med Coll Abbottabad, 2018, 30(Suppl 1)(4):S627-S632.
[34]	Trimboli P, Lauretta R, Barnabei A, et al. Procalcitonin as a postoperative marker in the follow-up of patients affected by medullary thyroid carcinoma[J]. Int J Biol Markers, 2018, 33(2):156-160. doi: 10.1177/1724600817747518 URL
[35]	Chen L, Sun W, Qian K, et al. High ratio of early postoperative calcitonin to preoperative calcitonin could be a novel indicator of poor prognosis in patients with biochemical incomplete responses in sporadic medullary thyroid cancer[J]. Endocr Pract, 2020, 26(7):738-747. doi: 10.4158/EP-2019-0404 URL

风险	密码子突变	手术时间	手术方式（TT±CND）
最高风险	M918TA883F^a）	<1岁	无LNM且PIS或PAT,加CND
高风险	C634A883F	<5岁	Ctn>40 ng/L或LNM,加CND
中风险	其他突变	≥5岁	Ctn↑或LNM,加CND