Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Case Report

Multiple Endocrine Neoplasia Type 2B Associated Mixed Medullary and Follicular Thyroid Carcinoma in A Chinese Patient with RET M918T Germline Mutation

Author(s): Xiao-Ping Qi, Guo-Bing Lin, Bo Chen, Feng Li, Zhi-Lie Cao, Wei-Hui Zheng and Jian-Qiang Zhao*

Volume 21, Issue 3, 2021

Published on: 13 July, 2020

Page: [554 - 560] Pages: 7

DOI: 10.2174/1871530320666200713092633

Price: $65

Abstract

Background: Mixed medullary and follicular thyroid carcinoma (MMFC) displays heterogeneous morphological components and immunophenotypical features intermingled within the same lesion, which is rare and most described in the sporadic form. We report herein a Chinese patient with multiple endocrine neoplasia type 2B (MEN2B) harboring germline RET M918T and associated MMFC.

Methods: A case of a 39-year-old male patient with MEN2B presented palpable neck masses in both thyroid lobes (maximum sizes: left, 3.9 cm; right, 5.4 cm) and a definitive phenotype. Serum levels of calcitonin (Ctn; >2000pg/mL), carcinoembryonic antigen (CEA; 719.27ng/mL), and thyroglobulin (Tg; 98.54ng/mL) were high. Fine-needle aspiration cytology showed features positive for malignancy, suggesting the possibility of medullary thyroid carcinoma (MTC). Total thyroidectomy, along with extending bilateral neck lymph nodes dissection, and subsequently, genetics family screening were performed.

Results: The histopathological examination yielded a diagnosis of MMFC that showed immunohistochemical characteristic patterns of the component of MTC positive for Ctn and CEA, chromogranin A, and the follicular carcinoma components were positive for Tg. Lymph node metastasis was observed showing medullary tumoral cells positive for Ctn and follicular-like structures lacking tumor cells positive for Tg staining (T4bN1bM0). Genetics screening confirmed RET M918T (c.2753T>C) mutation manifested in the patient but was not detected in other family members. Follow up showed that the serum Ctn, CEA and Tg levels respectively dropped to 54.38pg/ml, 4.16ng/mL and 0.04ng/mL 16 months after the surgery.

Conclusion: Particular and diverse patterns of MMFC should be recognized with immunostaining features. MMFC occurring in a patient with MEN2B harboring RET M918T may be unique biological behavior and the treatment is mostly radical surgery.

Keywords: Thyroid neoplasm, medullary thyroid carcinoma, mixed medullary-follicular carcinoma, multiple endocrine neoplasia type 2B, RET proto-oncogene, M918T mutation.

« Previous Next »
Graphical Abstract

[1]
Wells, S.A., Jr; Asa, S.L.; Dralle, H.; Elisei, R.; Evans, D.B.; Gagel, R.F.; Lee, N.; Machens, A.; Moley, J.F.; Pacini, F.; Raue, F.; Frank-Raue, K.; Robinson, B.; Rosenthal, M.S.; Santoro, M.; Schlumberger, M.; Shah, M.; Waguespack, S.G. 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(6), 567-610.
[http://dx.doi.org/10.1089/thy.2014.0335] [PMID: 25810047]
[2]
Elisei, R.; Alevizaki, M.; Conte-Devolx, B.; Frank-Raue, K.; Leite, V.; Williams, G.R. 2012 European thyroid association guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur. Thyroid J., 2013, 1(4), 216-231.
[http://dx.doi.org/10.1159/000346174] [PMID: 24783025]
[3]
Brauckhoff, M.; Machens, A.; Lorenz, K.; Bjøro, T.; Varhaug, J.E.; Dralle, H. Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective. Ann. Surg., 2014, 259(4), 800-806.
[http://dx.doi.org/10.1097/SLA.0b013e3182a6f43a] [PMID: 23979292]
[4]
Raue, F.; Dralle, H.; Machens, A.; Bruckner, T.; Frank-Raue, K. Long-term survivorship in multiple endocrine neoplasia type 2B diagnosed before and in the new millennium. J. Clin. Endocrinol. Metab., 2018, 103(1), 235-243.
[http://dx.doi.org/10.1210/jc.2017-01884] [PMID: 29077903]
[5]
Tohidi, M.; Pourbehi, G.; Bahmanyar, M.; Eghbali, S.S.; Kalantar Hormozi, M.; Nabipour, I. Mixed medullary-follicular carcinoma of the thyroid. Case Rep. Endocrinol., 2013.2013571692
[http://dx.doi.org/10.1155/2013/571692] [PMID: 24288632]
[6]
Ben Salah, R.; Mekni, A.; Doghri, R.; Kchir, N.; Haouet, S.; Besbes, G.; Bouchoucha, S.; Zitouna, M. A mixed medullary-follicular thyroid carcinoma discovered by fine needle aspiration. Tunis. Med., 2012, 90(6), 488-490.
[PMID: 22693094]
[7]
Hanna, A.N.; Michael, C.W.; Jing, X. Mixed medullary-follicular carcinoma of the thyroid: diagnostic dilemmas in fine-needle aspiration cytology. Diagn. Cytopathol., 2011, 39(11), 862-865.
[http://dx.doi.org/10.1002/dc.21560] [PMID: 21994201]
[8]
Qi, X.P.; Chen, X.L.; Ma, J.M.; Du, Z.F.; Fei, J.; Yang, C.P.; Cheng, J.; Song, Q.Z.; Han, J.S.; Jin, H.Y.; Chen, Z.G.; Wang, J.Q.; Yang, Y.P.; Ying, R.B.; Liu, W.T.; Zhao, Y.; Chen, C.Y.; Jiang, H.L.; Ke, H.P.; Zhang, X.N. RET proto-oncogene genetic screening of families with multiple endocrine neoplasia type 2 optimizes diagnostic and clinical management in China. Thyroid, 2012, 22(12), 1257-1265.
[http://dx.doi.org/10.1089/thy.2012.0134] [PMID: 23210566]
[9]
Qi, X.P.; Ying, R.B.; Ma, J.M.; Liu, W.T.; Du, Z.F.; Fei, J.; Yang, C.P.; Song, Q.Z.; Jin, H.Y.; Chen, Z.G.; Han, J.S.; Wang, J.Q.; Chen, X.L.; Zhao, Y.; Lu, J.J.; Zhang, X.N. Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma. Fam. Cancer, 2012, 11(1), 131-136.
[http://dx.doi.org/10.1007/s10689-011-9487-1] [PMID: 22068382]
[10]
Volante, M.; Papotti, M.; Roth, J.; Saremaslani, P.; Speel, E.J.; Lloyd, R.V.; Carney, J.A.; Heitz, P.U.; Bussolati, G.; Komminoth, P. Mixed medullary-follicular thyroid carcinoma. Molecular evidence for a dual origin of tumor components. Am. J. Pathol., 1999, 155(5), 1499-1509.
[http://dx.doi.org/10.1016/S0002-9440(10)65465-X] [PMID: 10550306]
[11]
Frank-Raue, K.; Döhring, J.; Scheumann, G.; Rondot, S.; Lorenz, A.; Schulze, E.; Dralle, H.; Raue, F.; Leidig-Bruckner, G. New mutations in the RET protooncogene-L881V - associated with medullary thyroid carcinoma and -R770Q - in a patient with mixed medullar/follicular thyroid tumour. Exp. Clin. Endocrinol. Diabetes, 2010, 118(8), 550-553.
[http://dx.doi.org/10.1055/s-0029-1241851] [PMID: 20013610]
[12]
Orlandi, F.; Chiefari, E.; Caraci, P.; Mussa, A.; Gonzatto, I.; De Giuli, P.; Giuffrida, D.; Angeli, A.; Filetti, S. RET proto-oncogene mutation in a mixed medullary-follicular thyroid carcinoma. J. Endocrinol. Invest., 2001, 24(1), 51-55.
[http://dx.doi.org/10.1007/BF03343809] [PMID: 11227733]
[13]
Ueki, I.; Ando, T.; Haraguchi, A.; Horie, I.; Imaizumi, M.; Hayashi, T.; Uga, T.; Usa, T.; Kawakami, A. A case of mixed medullary and follicular cell carcinoma of the thyroid. Intern. Med., 2011, 50(12), 1313-1316.
[http://dx.doi.org/10.2169/internalmedicine.50.4749] [PMID: 21673468]
[14]
Shimizu, M.; Hirokawa, M. LiVolsi, V.A.; Mizukami, Y.; Harada, T.; Itoh, T.; Manabe, T. Combined “mixed medullary-follicular” and “papillary” carcinoma of the thyroid with lymph node metastasis. Endocr. Pathol., 2000, 11(4), 353-358.
[http://dx.doi.org/10.1385/EP:11:4:353] [PMID: 12114759]
[15]
Hewavisenthi, S.J.; Ariyarathne, J.; Gunawardena, P.A. Mixed medullary follicular carcinoma--an unusual thyroid neoplasm. Ceylon Med. J., 2000, 45(1), 34-35.
[http://dx.doi.org/10.4038/cmj.v45i1.7955] [PMID: 11006619]
[16]
Kostoglou-Athanassiou, I.; Athanassiou, P.; Vecchini, G.; Gogou, L.; Kaldrymides, P. Mixed medullary-follicular thyroid carcinoma. Report of a case and review of the literature. Horm. Res., 2004, 61(6), 300-304.
[http://dx.doi.org/10.1159/000078576] [PMID: 15153799]
[17]
Bhatnagar, P.; Bhatnagar, A.; Kishan, S.; Bal, C.S.; Saran, R.K.; Sinha, S.; Kashyap, R. Unusual widespread metastatic presentation of mixed medullary-follicular thyroid carcinoma. Clin. Nucl. Med., 2004, 29(5), 303-305.
[http://dx.doi.org/10.1097/01.rlu.0000122802.64681.2d] [PMID: 15069329]
[18]
Maruna, P.; Duskova, J.; Limanova, Z.; Dvoraková, S.; Vaclavikova, E.; Bendlova, B. Mixed medullary and follicular cell carcinoma of the thyroid in a 71-year-old man with history of malignant melanoma. Med. Sci. Monit., 2008, 14(4), CS31-CS36.
[PMID: 18376354]
[19]
Sadow, P.M.; Hunt, J.L. Mixed Medullary-follicular-derived carcinomas of the thyroid gland. Adv. Anat. Pathol., 2010, 17(4), 282-285.
[http://dx.doi.org/10.1097/PAP.0b013e3181e4ab3e] [PMID: 20574174]
[20]
Hsieh, M.H.; Lin, M.C.; Shun, C.T.; Chang, T.C. Fine needle aspiration cytology of mixed medullary-follicular thyroid carcinoma: a case report. Acta Cytol., 2008, 52(3), 361-365.
[http://dx.doi.org/10.1159/000325524] [PMID: 18540307]
[21]
Cakir, M.; Altunbas, H.; Balci, M.K.; Karayalcin, U.; Karpuzoglu, G. Medullary thyroid carcinoma, follicular variant. Endocr. Pathol., 2002, 13(1), 75-79.
[http://dx.doi.org/10.1385/EP:13:1:75] [PMID: 12114753]
[22]
Dusková, J.; Janotová, D.; Svobodová, E.; Novák, Z.; Tretiník, P. Fine needle aspiration biopsy of mixed medullary-follicular thyroid carcinoma. A report of two cases. Acta Cytol., 2003, 47(1), 71-77.
[http://dx.doi.org/10.1159/000326478] [PMID: 12585034]
[23]
Mizukami, Y.; Michigishi, T.; Nonomura, A.; Nakamura, S.; Noguchi, M.; Hashimoto, T.; Itoh, N. Mixed medullary-follicular carcinoma of the thyroid occurring in familial form. Histopathology, 1993, 22(3), 284-287.
[http://dx.doi.org/10.1111/j.1365-2559.1993.tb00123.x] [PMID: 8495962]
[24]
Kovacs, C.S.; Masé, R.M.; Kovacs, K.; Nguyen, G.K.; Chik, C.L. Thyroid medullary carcinoma with thyroglobulin immunoreactivity in sporadic multiple endocrine neoplasia type 2-B. Cancer, 1994, 74(3), 928-932.
[http://dx.doi.org/10.1002/1097-0142(19940801)74:3<928:AID-CNCR2820740321>3.0.CO;2-E] [PMID: 7913660]
[25]
Papotti, M.; Volante, M.; Komminoth, P.; Sobrinho-Simões, M.; Bussolati, G. Thyroid carcinomas with mixed follicular and C-cell differentiation patterns. Semin. Diagn. Pathol., 2000, 17(2), 109-119.
[PMID: 10839611]
[26]
Papotti, M.; Negro, F.; Carney, J.A.; Bussolati, G.; Lloyd, R.V. Mixed medullary-follicular carcinoma of the thyroid. A morphological, immunohistochemical and in situ hybridization analysis of 11 cases. Virchows Arch., 1997, 430(5), 397-405.
[http://dx.doi.org/10.1007/s004280050049] [PMID: 9174630]
[27]
Noel, M.; Delehaye, M.C.; Segond, N.; Lasmoles, F.; Caillou, B.; Gardet, P.; Fragu, P.; Moukhtar, M.S. Study of calcitonin and thyroglobulin gene expression in human mixed follicular and medullary thyroid carcinoma. Thyroid, 1991, 1(3), 249-256.
[http://dx.doi.org/10.1089/thy.1991.1.249] [PMID: 1824340]
[28]
Lloyd, R.V.; Osamura, R.Y.; Klöppel, G.; Rosai, J. WHO Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs; IARC Press: Lyon, 2017.
[29]
Erhamamci, S.; Reyhan, M.; Kocer, N.E.; Nursal, G.N.; Torun, N.; Yapar, A.F. Simultaneous occurrence of medullary and differentiated thyroid carcinomas. Report of 4 cases and brief review of the literature. Hell. J. Nucl. Med., 2014, 17(2), 148-152.
[http://dx.doi.org/10.1967/s002449910137] [PMID: 24997082]
[30]
Tanaka, T.; Yoshimi, N.; Kanai, N.; Mori, H.; Nagai, K.; Fujii, A.; Sakata, S.; Tokimitsu, N. Simultaneous occurrence of medullary and follicular carcinoma in the same thyroid lobe. Hum. Pathol., 1989, 20(1), 83-86.
[http://dx.doi.org/10.1016/0046-8177(89)90208-6] [PMID: 2912879]
[31]
Nangue, C.; Bron, L.; Portmann, L.; Volante, M.; Ris, H.B.; Monnier, P.; Andrejevic-Blant, S. Mixed medullary-papillary carcinoma of the thyroid: report of a case and review of the literature. Head Neck, 2009, 31(7), 968-974.
[http://dx.doi.org/10.1002/hed.20984] [PMID: 19260112]
[32]
Wong, R.L.; Kazaure, H.S.; Roman, S.A.; Sosa, J.A. Simultaneous medullary and differentiated thyroid cancer: a population-level analysis of an increasingly common entity. Ann. Surg. Oncol., 2012, 19(8), 2635-2642.
[http://dx.doi.org/10.1245/s10434-012-2357-8] [PMID: 22526904]
[33]
Liu, Y.; Yuan, L.; Yang, D.; Jin, Y. Serum calcitonin negative mixed medullary-follicular carcinoma initially diagnosed as medullary thyroid carcinoma by fine-needle aspiration cytology: A case report and review of the literatures. Diagn. Cytopathol., 2018, 46(8), 690-693.
[http://dx.doi.org/10.1002/dc.23924] [PMID: 29524315]
[34]
Lebeault, M.; Pinson, S.; Guillaud-Bataille, M.; Gimenez-Roqueplo, A.P.; Carrie, A.; Barbu, V.; Pigny, P.; Bezieau, S.; Rey, J.M.; Delvincourt, C.; Giraud, S.; Veyrat-Durebex, C.; Saulnier, P.; Bouzamondo, N.; Chabbert, M.; Blin, J.; Mohamed, A.; Romanet, P.; Borson-Chazot, F.; Rohmer, V.; Barlier, A.; Mirebeau-Prunier, D. Nationwide French study of RET variants detected from 2003 to 2013 suggests a possible influence of polymorphisms as modifiers. Thyroid, 2017, 27(12), 1511-1522.
[http://dx.doi.org/10.1089/thy.2016.0399] [PMID: 28946813]
[35]
Wells, S.A., Jr; Pacini, F.; Robinson, B.G.; Santoro, M. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J. Clin. Endocrinol. Metab., 2013, 98(8), 3149-3164.
[http://dx.doi.org/10.1210/jc.2013-1204] [PMID: 23744408]
[36]
Castinetti, F.; Waguespack, S.G.; Machens, A.; Uchino, S.; Hasse-Lazar, K.; Sanso, G.; Else, T.; Dvorakova, S.; Qi, X.P.; Elisei, R.; Maia, A.L.; Glod, J.; Lourenço, D.M., Jr; Valdes, N.; Mathiesen, J.; Wohllk, N.; Bandgar, T.R.; Drui, D.; Korbonits, M.; Druce, M.R.; Brain, C.; Kurzawinski, T.; Patocs, A.; Bugalho, M.J.; Lacroix, A.; Caron, P.; Fainstein-Day, P.; Borson Chazot, F.; Klein, M.; Links, T.P.; Letizia, C.; Fugazzola, L.; Chabre, O.; Canu, L.; Cohen, R.; Tabarin, A.; Spehar Uroic, A.; Maiter, D.; Laboureau, S.; Mian, C.; Peczkowska, M.; Sebag, F.; Brue, T.; Mirebeau-Prunier, D.; Leclerc, L.; Bausch, B.; Berdelou, A.; Sukurai, A.; Vlcek, P.; Krajewska, J.; Barontini, M.; Vaz Ferreira Vargas, C.; Valerio, L.; Ceolin, L.; Akshintala, S.; Hoff, A.; Godballe, C.; Jarzab, B.; Jimenez, C.; Eng, C.; Imai, T.; Schlumberger, M.; Grubbs, E.; Dralle, H.; Neumann, H.P.; Baudin, E. Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study. Lancet Diabetes Endocrinol., 2019, 7(3), 213-220.
[http://dx.doi.org/10.1016/S2213-8587(18)30336-X] [PMID: 30660595]
[37]
Qi, X.P.; Jin, B.Y.; Li, P.F.; Wang, S.; Zhao, Y.H.; Cao, Z.L.; Yu, X.H.; Cheng, J.; Fang, X.D.; Zhao, J.Q. RET S409Y Germline mutation and associated medullary thyroid carcinoma. Thyroid, 2019, 29(10), 1447-1456.
[http://dx.doi.org/10.1089/thy.2018.0385] [PMID: 31364476]

Rights & Permissions Print Cite
Article Metrics
39
1
© 2024 Bentham Science Publishers | Privacy Policy