Medullary Thyroid Cancer with Paraganglioma-Like Pattern Diagnosed During Pregnancy: A Case Report and Literature Revision

Author(s): Anna De Tullio, Giuseppe Lisco, Loren Duda, Giuseppina Renzulli, Vincenzo Triggiani*.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 20 , Issue 2 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Introduction: Medullary thyroid carcinoma (MTC) is an infrequent thyroid malignancy rarely observed and managed during pregnancy. An accurate diagnostic workup is extremely important in this clinical setting to correctly diagnose and treat the disease, avoiding both maternal and fetal complications.

Objective: We report our experience in managing an MTC incidentally diagnosed during pregnancy in a 28-year female, highlighting critical aspects through the diagnostic workup. Additionally, we provide a literature revision searching on PubMed terms related to “medullary thyroid carcinoma”, “primary thyroid paraganglioma”, “paraganglioma-like medullary thyroid cancer” in relationship with a nodular appearance at neck US, serum CT measurement, cytological and histological findings.

Methods: Specimens for cytological evaluation were stained with the Papanicolaou method while tissue sections were stained with hematoxylin and eosin and Congo red stain. Immunohistochemical evaluation was also performed for thyroid transcription factor-1, enolase, thyroglobulin, cytokeratin, chromogranin A, S-100 protein, glial fibrillary acidic protein, calcitonin and Ki-67.

Results: Serum CT was incidentally found to be elevated in two consecutive venous samples. However, the cytological assessment of the fine needle aspiration (FNAc) showed “cells with round-shaped nuclei and granular chromatin, organized to form nests or syncytial flaps, scattered among histocytes, and immunocytochemical positivity for CT, thyroid transcriptional factor-1, cytokeratin, S-100 protein”, highlighting a suspicion of both MTC and intrathyroidal paraganglioma. MTC was finally supposed after the evidence of a really elevated CT (3,726 pg/ml) measurement in the FNA washout fluid. After a careful discussion about both risks and benefits, the patient decided to postpone the surgery after the delivery.

Conclusion: The histological diagnosis finally confirmed a rare case of paraganglioma-like MTC (T1 N0 Mx), emphasizing the complexity of our differential diagnosis, between an MTC and a thyroidal paraganglioma. In similar cases, due to a relevant impact on surgical timing, patients should be adequately informed about both risk and benefits of the surgery during pregnancy, and a careful management of the disease is required until and after surgery.

Keywords: Medullary thyroid carcinoma, thyroid paraganglioma, paraganglioma-like medullary thyroid cancer, immunocytochemical, immunohistochemical, neck ultrasound.

[1]
Gibelli, B.; Zamperini, P.; Proh, M.; Giugliano, G. Management and follow-up of thyroid cancer in pregnant women. Acta Otorhinolaryngol. Ital., 2011, 31(6), 358-365.
[PMID: 22323846]
[2]
Yasmeen, S.; Cress, R.; Romano, P.S.; Xing, G.; Berger-Chen, S.; Danielsen, B.; Smith, L.H. Thyroid cancer in pregnancy. Int. J. Gynaecol. Obstet., 2005, 91(1), 15-20.
[http://dx.doi.org/10.1016/j.ijgo.2005.06.022] [PMID: 16085061]
[3]
Wells, S.A.J., 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]
[4]
Gilbert, H. Daniels. Screening for Medullary Thyroid Carcinoma with Serum Calcitonin Measurements in Patients with Thyroid Nodules in the United States and Canada. Thyroid, 2011, 21(11), 1199-1207.
[http://dx.doi.org/10.1089/thy.2010.0297] [PMID: 21936671]
[5]
Deftos, L.J. Should serum calcitonin be routinely measured in patients with thyroid nodules--will the law answer before endocrinologists do? J. Clin. Endocrinol. Metab., 2004, 89(9), 4768-4769.
[http://dx.doi.org/10.1210/jc.2004-0314] [PMID: 15356093]
[6]
Valderrabano, P.; Klippenstein, D.L.; Tourtelot, J.B.; Ma, Z.; Thompson, Z.J.; Lilienfeld, H.S.; McIver, B. New American Thyroid Association Sonographic Patterns for Thyroid Nodules Perform Well in Medullary Thyroid Carcinoma: Institutional Experience, Systematic Review, and Meta-Analysis. Thyroid, 2016, 26(8), 1093-1100.
[http://dx.doi.org/10.1089/thy.2016.0196] [PMID: 27267210]
[7]
Woliński, K.; Rewaj-Łosyk, M.; Ruchała, M. Sonographic features of medullary thyroid carcinomas--a systematic review and meta-analysis. Endokrynol. Pol., 2014, 65(4), 314-318.
[PMID: 25185855]
[8]
Liu, M.J.; Liu, Z.F.; Hou, Y.Y.; Men, Y.M.; Zhang, Y.X.; Gao, L.Y.; Liu, H. Ultrasonographic characteristics of medullary thyroid carcinoma: a comparison with papillary thyroid carcinoma. Oncotarget, 2017, 8(16), 27520-27528.
[http://dx.doi.org/10.18632/oncotarget.15897] [PMID: 28460476]
[9]
Lai, X.; Liu, M.; Xia, Y.; Wang, L.; Bi, Y.; Li, X.; Zhang, B.; Yang, M.; Dai, Q.; Jiang, Y. Hypervascularity is more frequent in medullary thyroid carcinoma: Compared with papillary thyroid carcinoma. Medicine (Baltimore), 2016, 95(49)e5502
[http://dx.doi.org/10.1097/MD.0000000000005502] [PMID: 27930537]
[10]
Bao, S.D.; Pang, P.; Zang, L.; Chen, K.; Gu, W.J.; Yang, G.Q.; Du, J.; Tian, W.; Luo, Y.K.; Lü, Z.H.; Dou, J.T.; Mu, Y.M. [Predictive value of sonographic features in preoperative evaluation of medullary thyroid carcinoma. Zhonghua Yi Xue Za Zhi, 2016, 96(31), 2482-2486.
[PMID: 27562047]
[11]
Trimboli, P.; Nasrollah, N.; Amendola, S.; Rossi, F.; Ramacciato, G.; Romanelli, F.; Aurello, P.; Crescenzi, A.; Laurenti, O.; Condorelli, E.; Ventura, C.; Valabrega, S. Should we use ultrasound features associated with papillary thyroid cancer in diagnosing medullary thyroid cancer? Endocr. J., 2012, 59(6), 503-508.
[http://dx.doi.org/10.1507/endocrj.EJ12-0050] [PMID: 22447142]
[12]
Choi, N.; Moon, W.J.; Lee, J.H.; Baek, J.H.; Kim, D.W.; Park, S.W. Ultrasonographic findings of medullary thyroid cancer: differences according to tumor size and correlation with fine needle aspiration results. Acta Radiol., 2011, 52(3), 312-316.
[http://dx.doi.org/10.1258/ar.2010.100247] [PMID: 21498368]
[13]
Cai, S.; Liu, H.; Li, W.B.; Ouyang, Y.S.; Zhang, B.; Li, P.; Wang, X.L.; Zhang, X.Y.; Li, J.C.; Jiang, Y.X. Ultrasonographic features of medullary thyroid carcinoma and their diagnostic values. Chin. Med. J. (Engl.), 2010, 123(21), 3074-3078.
[PMID: 21162958]
[14]
Lee, S.; Shin, J.H.; Han, B.K.; Ko, E.Y. Medullary thyroid carcinoma: comparison with papillary thyroid carcinoma and application of current sonographic criteria. AJR Am. J. Roentgenol., 2010, 194(4), 1090-1094.
[http://dx.doi.org/10.2214/AJR.09.3276] [PMID: 20308516]
[15]
Kim, S.H.; Kim, B.S.; Jung, S.L.; Lee, J.W.; Yang, P.S.; Kang, B.J.; Lim, H.W.; Kim, J.Y.; Whang, I.Y.; Kwon, H.S.; Jung, C.K. Ultrasonographic findings of medullary thyroid carcinoma: a comparison with papillary thyroid carcinoma. Korean J. Radiol., 2009, 10(2), 101-105.
[http://dx.doi.org/10.3348/kjr.2009.10.2.101] [PMID: 19270854]
[16]
Saller, B.; Moeller, L.; Görges, R.; Janssen, O.E.; Mann, K. Role of conventional ultrasound and color Doppler sonography in the diagnosis of medullary thyroid carcinoma. Exp. Clin. Endocrinol. Diabetes, 2002, 110(8), 403-407.
[http://dx.doi.org/10.1055/s-2002-36546] [PMID: 12518251]
[17]
Yu, B.H.; Sheng, W.Q.; Wang, J. Primary paraganglioma of thyroid gland: a clinicopathologic and immunohistochemical analysis of three cases with a review of the literature. Head Neck Pathol., 2013, 7(4), 373-380.
[http://dx.doi.org/10.1007/s12105-013-0467-7] [PMID: 23943066]
[18]
Andrioli, M.; Carzaniga, C.; Persani, L. Standardized Ultrasound Report for Thyroid Nodules: The Endocrinologist’s Viewpoint. Eur. Thyroid J., 2013, 2(1), 37-48.
[http://dx.doi.org/10.1159/000347144] [PMID: 24783037]
[19]
Gharib, H.; Papini, E.; Garber, J.R.; Duick, D.S.; Harrell, R.M.; Hegedüs, L.; Paschke, R.; Valcavi, R.; Vitti, P. AACE/ACE/AME Task Force on Thyroid Nodules. American Association Of Clinical Endocrinologists, American College Of Endocrinology, And Associazione Medici Endocrinologi Medical Guidelines For Clinical Practice For The Diagnosis And Management Of Thyroid Nodules--2016 Update. Endocr. Pract., 2016, 22(5), 622-639.
[http://dx.doi.org/10.4158/EP161208.GL] [PMID: 27167915]
[20]
Deftos, L.J.; Lee, M.R.; Potts, J.T. Jr A radioimmunoassay for thyrocalcitonin. Proc. Natl. Acad. Sci. USA, 1968, 60(1), 293-299.
[http://dx.doi.org/10.1073/pnas.60.1.293] [PMID: 4173038]
[21]
Fugazzola, L. Stimulated calcitonin cut-offs by different tests. Eur. Thyroid J., 2013, 2(1), 49-56.
[PMID: 24783038]
[22]
Elisei, R.; Bottici, V.; Luchetti, F.; Di Coscio, G.; Romei, C.; Grasso, L.; Miccoli, P.; Iacconi, P.; Basolo, F.; Pinchera, A.; Pacini, F. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J. Clin. Endocrinol. Metab., 2004, 89(1), 163-168.
[http://dx.doi.org/10.1210/jc.2003-030550] [PMID: 14715844]
[23]
Bugalho, M.J.; Santos, J.R.; Sobrinho, L. Preoperative diagnosis of medullary thyroid carcinoma: fine needle aspiration cytology as compared with serum calcitonin measurement. J. Surg. Oncol., 2005, 91(1), 56-60.
[http://dx.doi.org/10.1002/jso.20269] [PMID: 15999359]
[24]
Turk, Y.; Makay, O.; Ozdemir, M.; Ertunc, G.; Demir, B.; Icoz, G.; Akyildiz, M.; Yilmaz, M. Routine calcitonin measurement in nodular thyroid disease management: is it worthwhile? Ann. Surg. Treat. Res., 2017, 92(4), 173-178.
[http://dx.doi.org/10.4174/astr.2017.92.4.173] [PMID: 28382288]
[25]
Rosario, P.W.; Calsolari, M.R. Usefulness of Serum Calcitonin in Patients Without a Suspicious History of Medullary Thyroid Carcinoma and with Thyroid Nodules Without an Indication for Fine-Needle Aspiration or with Benign Cytology. Horm. Metab. Res., 2016, 48(6), 372-276.
[http://dx.doi.org/10.1055/s-0042-107246] [PMID: 27203410]
[26]
Costante, G.; Meringolo, D.; Durante, C.; Bianchi, D.; Nocera, M.; Tumino, S.; Crocetti, U.; Attard, M.; Maranghi, M.; Torlontano, M.; Filetti, S. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J. Clin. Endocrinol. Metab., 2007, 92(2), 450-455.
[http://dx.doi.org/10.1210/jc.2006-1590] [PMID: 17119000]
[27]
d’Herbomez, M.; Caron, P.; Bauters, C.; Do Cao, C.; Schlienger, J.L.; Sapin, R.; Baldet, L.; Carnaille, B.; Wémeau, J.L. French Group GTE (Groupe des Tumeurs Endocrines). Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking. Eur. J. Endocrinol., 2007, 157(6), 749-755.
[http://dx.doi.org/10.1530/EJE-07-0566] [PMID: 18057382]
[28]
Cipri, C.; Vescini, F.; Torresan, F.; Pennelli, G.; Pelizzo, M.R.; Triggiani, V.; Guastamacchia, E.; Grimaldi, F. An Unusual Case of Medullary Thyroid Carcinoma and A Revision of Current Literature. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(2), 226-229.
[http://dx.doi.org/10.2174/1871530319666181220165350] [PMID: 30574858]
[29]
Haugen, B.R.; Alexander, E.K.; Bible, K.C.; Doherty, G.M.; Mandel, S.J.; Nikiforov, Y.E.; Pacini, F.; Randolph, G.W.; Sawka, A.M.; Schlumberger, M.; Schuff, K.G.; Sherman, S.I.; Sosa, J.A.; Steward, D.L.; Tuttle, R.M.; Wartofsky, L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 2016, 26(1), 1-133.
[http://dx.doi.org/10.1089/thy.2015.0020] [PMID: 26462967]
[30]
Costante, G.; Filetti, S. Early diagnosis of medullary thyroid carcinoma: is systematic calcitonin screening appropriate in patients with nodular thyroid disease? Oncologist, 2011, 16(1), 49-52.
[http://dx.doi.org/10.1634/theoncologist.2010-0344] [PMID: 21212427]
[31]
Vannucchi, G.; Covelli, D.; Vigo, B.; Perrino, M.; Mondina, L.; Fugazzola, L. Thyroid volume and serum calcitonin changes during pregnancy. J. Endocrinol. Invest., 2017, 40(7), 727-732.
[http://dx.doi.org/10.1007/s40618-017-0622-1] [PMID: 28229359]
[32]
Torres, D.A.; Freitas, M.B.; Gonçalves, R.V. Changes in bone turnover and calcium homeostasis during pregnancy and lactation in mammals: a meta-analysis. Reprod. Fertil. Dev., 2018, 30(5), 681-688.
[http://dx.doi.org/10.1071/RD17163] [PMID: 29136400]
[33]
Papaparaskeva, K.; Nagel, H.; Droese, M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. Diagn. Cytopathol., 2000, 22(6), 351-358.
[http://dx.doi.org/10.1002/(SICI)1097-0339(200006)22:6<351:AID-DC5>3.0.CO;2-T] [PMID: 10820528]
[34]
Kaushal, S.; Iyer, V.K.; Mathur, S.R.; Ray, R. Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases. Cytopathology, 2011, 22(2), 95-105.
[http://dx.doi.org/10.1111/j.1365-2303.2010.00747.x] [PMID: 20518799]
[35]
Trimboli, P.; Treglia, G.; Guidobaldi, L.; Romanelli, F.; Nigri, G.; Valabrega, S.; Sadeghi, R.; Crescenzi, A.; Faquin, W.C.; Bongiovanni, M.; Giovanella, L. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin. Endocrinol. (Oxf.), 2015, 82(2), 280-285.
[http://dx.doi.org/10.1111/cen.12563] [PMID: 25047365]
[36]
Phitayakorn, R.; Faquin, W.; Wei, N.; Barbesino, G.; Stephen, A.E. Thyroid-associated paragangliomas. Thyroid, 2011, 21(7), 725-733.
[http://dx.doi.org/10.1089/thy.2010.0362] [PMID: 21615305]
[37]
Lee, S.M.; Policarpio-Nicolas, M.L.C. Thyroid Paraganglioma. Arch. Pathol. Lab. Med., 2015, 139(8), 1062-1067.
[http://dx.doi.org/10.5858/arpa.2013-0703-RS] [PMID: 26230601]
[38]
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]
[39]
Jayaram, G.; Hayati, J.N.; Yip, C.H.; Ranganathan, S.; Taib, N.A. Cytologic, histologic and immunocytochemical features in fine needle aspiration of paraganglioma-like variant of medullary carcinoma. Acta Cytol., 2008, 52(1), 119-121.
[http://dx.doi.org/10.1159/000325449] [PMID: 18323289]
[40]
Bockhorn, M.; Sheu, S-Y.; Frilling, A.; Molmenti, E.; Schmid, K.W.; Broelsch, C.E. Paraganglioma-like medullary thyroid carcinoma: a rare entity. Thyroid, 2005, 15(12), 1363-1367.
[http://dx.doi.org/10.1089/thy.2005.15.1363] [PMID: 16405409]
[41]
Magro, G.; Grasso, S. Sustentacular cells in sporadic paraganglioma-like medullary thyroid carcinoma: report of a case with diagnostic and histogenetic considerations. Pathol. Res. Pract., 2000, 196(1), 55-59.
[http://dx.doi.org/10.1016/S0344-0338(00)80022-9] [PMID: 10674273]
[42]
Ikeda, T.; Satoh, M.; Azuma, K.; Sawada, N.; Mori, M. Medullary thyroid carcinoma with a paraganglioma-like pattern and melanin production: a case report with ultrastructural and immunohistochemical studies. Arch. Pathol. Lab. Med., 1998, 122(6), 555-558.
[PMID: 9625426]
[43]
Yu, X.; Wang, Y.; Wang, P.; Ji, C.H.; Miao, C.D.; Zheng, S. Primary thyroid paraganglioma mimicking medullary thyroid carcinoma: A case report. Oncol. Lett., 2015, 10(2), 1000-1002.
[http://dx.doi.org/10.3892/ol.2015.3292] [PMID: 26622613]
[44]
Ryska, A.; Cap, J.; Vaclavikova, E.; Dvorakova, S.; Bendlova, B.; Hovorkova, E.; Kohout, A. Paraganglioma-like medullary thyroid carcinoma: fine needle aspiration cytology features with histological correlation. Cytopathology, 2009, 20(3), 188-194.
[http://dx.doi.org/10.1111/j.1365-2303.2008.00580.x] [PMID: 18631354]
[45]
Matias-Guiu, X.; Machin, P.; Pons, C.; Lagarda, E.; De Leiva, A.; Prat, J. Sustentacular cells occur frequently in the familial form of medullary thyroid carcinoma. J. Pathol., 1998, 184(4), 420-423.
[http://dx.doi.org/10.1002/(SICI)1096-9896(199804)184:4<420:AID-PATH1231>3.0.CO;2-R] [PMID: 9664909]
[46]
Trimboli, P.; Guidobaldi, L.; Bongiovanni, M.; Crescenzi, A.; Alevizaki, M.; Giovanella, L. Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: A systematic review. Diagn. Cytopathol., 2016, 44(1), 45-51.
[http://dx.doi.org/10.1002/dc.23375] [PMID: 26481456]
[47]
Diazzi, C.; Madeo, B.; Taliani, E.; Zirilli, L.; Romano, S.; Granata, A.R.; De Santis, M.C.; Simoni, M.; Cioni, K.; Carani, C.; Rochira, V. The diagnostic value of calcitonin measurement in wash-out fluid from fine-needle aspiration of thyroid nodules in the diagnosis of medullary thyroid cancer. Endocr. Pract., 2013, 19(5), 769-779.
[http://dx.doi.org/10.4158/EP12420.OR] [PMID: 23757613]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 2
Year: 2020
Page: [295 - 302]
Pages: 8
DOI: 10.2174/1871530319666190802142634
Price: $65

Article Metrics

PDF: 16
HTML: 3