Skip to main content

Advertisement

SpringerLink
Log in

Metachronous appearance of second malignancies in medullary thyroid carcinoma (MTC) patients: a diagnostic challenge and brief review of the literature

  • Mini Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Medullary thyroid carcinoma (MTC) is a rare tumour which frequently occurs in the context of the multiple endocrine neoplasia syndromes, where it coexists with other usually benign tumours. The clinical picture varies and distant metastases are frequently present at diagnosis. Calcitonin levels are elevated in the presence of metastatic disease. Two MTC cases are presented, which had elevated postoperative calcitonin levels. Imaging revealed lung lesions which were originally attributed to metastatic disease from the MTC. However, at follow-up, these cases presented unusual features. The rapid increase in the lung lesions and the development of hypercalcaemia in the first patient suggested a second unrelated tumour. Biopsy of the lung lesion was compatible with lung adenocarcinoma. In the second patient, the appearance of a liver mass, although calcitonin levels remained stable, led to biopsy of the lesion: this was negative for calcitonin and compatible with metastatic lung adenocarcinoma. These MTC cases show that further malignancies may coexist with MTC and may obscure the clinical picture and influence the therapeutic decisions, especially in the case of metastatic disease. Features such as unusual imaging characteristics and the development of hypercalcemia, never encountered in MTC outside the MEN2 syndromes, as well as ‘disproportionately’ low calcitonin levels, incompatible with extensive metastatic disease, were the factors that led to further work-up. Both the cases subsequently proved to carry an unsuspected second malignancy. It is crucial to discriminate the metastatic lesion attributed to MTC from another coexisting primary malignancy, because different therapeutic strategies are needed for each setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. S. Leboulleux, E. Baudin, J.P. Travagli, M. Schlumberger, Medullary thyroid carcinoma. Clin. Endocrinol. (Oxf). 61(3), 299–310 (2004). doi:10.1111/j.1365-2265.2004.02037.x

    Article  PubMed  Google Scholar 

  2. E. Modigliani, R. Cohen, J.M. Campos, B. Conte-Devolx, B. Maes, A. Boneu, M. Schlumberger, J.C. Bigorgne, P. Dumontier, L. Leclerc, B. Corcuff, I. Guilhem, Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin. Endocrinol. (Oxf). 48(3), 265–273 (1998)

    Article  PubMed  CAS  Google Scholar 

  3. E. Kebebew, P.H. Ituarte, A.E. Siperstein, Q.Y. Duh, O.H. Clark, Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer 88(5), 1139–1148 (2000). doi:10.1002/(SICI)1097-0142(20000301)88:5<1139:AID-CNCR26>3.0.CO;2-Z

    Article  PubMed  CAS  Google Scholar 

  4. M. Alevizaki, K. Saltiki, G. Rentziou, A. Papathoma, L. Sarika, V. Vasileiou, E. Anastasiou, Medullary thyroid carcinoma: the influence of policy changing in clinical characteristics and disease progression. Eur. J. Endocrinol. 167(6), 799–808 (2012). doi:10.1530/EJE-12-0388

    Article  PubMed  CAS  Google Scholar 

  5. R.T. Kloos, C. Eng, D.B. Evans, G.L. Francis, R.F. Gagel, H. Gharib, J.F. Moley, F. Pacini, M.D. Ringel, M. Schlumberger, S.A. Wells Jr, Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19(6), 565–612 (2009). doi:10.1089/thy.2008.0403

    Article  PubMed  Google Scholar 

  6. S. Hasani-Ranjbar, M.M. Amoli, Mutation screening of RET proto-oncogene in a family with medullary thyroid carcinoma, marfanoid habitus and pheochromocytoma; from clinically MEN2B to genetically MEN2A syndrome. Endocrine (2012). doi:10.1007/s12020-012-9610-6

    Google Scholar 

  7. S. Mastroianno, M. Torlontano, A. Scillitani, L. D’Aloiso, A. Verrienti, N. Bonfitto, A. De Bonis, L. D’Agruma, L.A. Muscarella, V. Guarnieri, F. Dicembrino, M. Maranghi, C. Durante, S. Filetti, Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family. Endocrine 40(3), 481–485 (2011). doi:10.1007/s12020-011-9501-2

    Article  PubMed  CAS  Google Scholar 

  8. W.G. Kim, G. Gong, E.Y. Kim, T.Y. Kim, S.J. Hong, W.B. Kim, Y.K. Shong, Concurrent occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma in the same thyroid should be considered as coincidental. Clin. Endocrinol. (Oxf). 72(2), 256–263 (2010). doi:10.1111/j.1365-2265.2009.03622.x

    Article  PubMed  Google Scholar 

  9. R.L. Wong, H.S. Kazaure, S.A. Roman, J.A. Sosa, Simultaneous medullary and differentiated thyroid cancer: a population-level analysis of an increasingly common entity. Ann. Surg. Oncol. 19(8), 2635–2642 (2012). doi:10.1245/s10434-012-2357-8

    Article  PubMed  Google Scholar 

  10. A. Machens, H. Dralle, Simultaneous medullary and papillary thyroid cancer: a novel entity? Ann. Surg. Oncol. 19(1), 37–44 (2012). doi:10.1245/s10434-011-1795-z

    Article  PubMed  Google Scholar 

  11. S. Rossi, L. Fugazzola, L. De Pasquale, P. Braidotti, V. Cirello, P. Beck-Peccoz, S. Bosari, A. Bastagli, Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumour: report of three cases with molecular analysis and review of the literature. Endocr. Relat. Cancer 12(2), 281–289 (2005). doi:10.1677/erc.1.00901

    Article  PubMed  CAS  Google Scholar 

  12. R.P. Biscolla, C. Ugolini, M. Sculli, V. Bottici, M.G. Castagna, C. Romei, B. Cosci, E. Molinaro, P. Faviana, F. Basolo, P. Miccoli, F. Pacini, A. Pinchera, R. Elisei, Medullary and papillary tumours are frequently associated in the same thyroid gland without evidence of reciprocal influence in their biologic behavior. Thyroid 14(11), 946–952 (2004). doi:10.1089/thy.2004.14.946

    Article  PubMed  Google Scholar 

  13. F. Bertagna, G. Treglia, A. Piccardo, E. Giovannini, G. Bosio, G. Biasiotto, E.K. Bahij, R. Maroldi, R. Giubbini, F18-FDG-PET/CT thyroid incidentalomas: a wide retrospective analysis in three Italian centres on the significance of focal uptake and SUV value. Endocrine (2012). doi:10.1007/s12020-012-9837-2

    PubMed  Google Scholar 

  14. A. Bocian, J. Kopczynski, P. Rieske, S. Piaskowski, J. Sluszniak, D. Kupnicka, S. Gozdz, A. Kowalska, J. Sygut, Simultaneous occurrence of medullary and papillary carcinomas of the thyroid gland with metastases of papillary carcinoma to the cervical lymph nodes and the coinciding small B-cell lymphocytic lymphoma of the lymph nodes: a case report. Pol. J. Pathol. 55(3), 23–30 (2004)

    PubMed  Google Scholar 

  15. M.F. Saad, N.G. Ordonez, R.K. Rashid, J.J. Guido, C.S. Hill Jr, R.C. Hickey, N.A. Samaan, Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 63(6), 319–342 (1984)

    CAS  Google Scholar 

  16. T. Papajik, M. Myslivecek, Z. Sedova, E. Buriankova, V. Prochazka, L. Raida, Z. Kubova, C. Neoral, D. Starostka, P. Mikula, B. Melichar, L. Kucerova, M. Tichy, K. Indrak, Synchronous second primary neoplasms detected by initial staging F-18 FDG PET/CT examination in patients with non-Hodgkin lymphoma. Clin. Nucl. Med. 36(7), 509–512 (2011). doi:10.1097/RLU.0b013e318217541d

    Article  PubMed  Google Scholar 

  17. L.B. Travis, C.S. Rabkin, L.M. Brown, J.M. Allan, B.P. Alter, C.B. Ambrosone, C.B. Begg, N. Caporaso, S. Chanock, A. DeMichele, W.D. Figg, M.K. Gospodarowicz, E.J. Hall, M. Hisada, P. Inskip, R. Kleinerman, J.B. Little, D. Malkin, A.K. Ng, K. Offit, C.H. Pui, L.L. Robison, N. Rothman, P.G. Shields, L. Strong, T. Taniguchi, M.A. Tucker, M.H. Greene, Cancer survivorship: genetic susceptibility and second primary cancers: research strategies and recommendations. J. Natl Cancer Inst. 98(1), 15–25 (2006). doi:10.1093/jnci/djj001

    Article  PubMed  Google Scholar 

  18. S.A. Wells Jr, B.G. Robinson, R.F. Gagel, H. Dralle, J.A. Fagin, M. Santoro, E. Baudin, R. Elisei, B. Jarzab, J.R. Vasselli, J. Read, P. Langmuir, A.J. Ryan, M.J. Schlumberger, Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J. Clin. Oncol. 30(2), 134–141 (2012). doi:10.1200/JCO.2011.35.5040

    Article  PubMed  CAS  Google Scholar 

  19. K.I. Alexandraki, G. Kaltsas, Gastroenteropancreatic neuroendocrine tumours: new insights in the diagnosis and therapy. Endocrine 41(1), 40–52 (2012). doi:10.1007/s12020-011-9562-2

    Article  PubMed  CAS  Google Scholar 

  20. H.L. Sarika, A. Papathoma, M. Garofalaki, V. Vasileiou, B. Vlassopoulou, E. Anastasiou, M. Alevizaki, High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece. Clin. Endocrinol. (Oxf). 77(6), 857–862 (2012). doi:10.1111/j.1365-2265.2012.04462.x

    Article  PubMed  CAS  Google Scholar 

  21. A.C. Antoniou, D.F. Easton, Models of genetic susceptibility to breast cancer. Oncogene 25(43), 5898–5905 (2006). doi:10.1038/sj.onc.1209879

    Article  PubMed  CAS  Google Scholar 

  22. P. Lichtenstein, N.V. Holm, P.K. Verkasalo, A. Iliadou, J. Kaprio, M. Koskenvuo, E. Pukkala, A. Skytthe, K. Hemminki, Environmental and heritable factors in the causation of cancer: analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343(2), 78–85 (2000). doi:10.1056/NEJM200007133430201

    Article  PubMed  CAS  Google Scholar 

  23. R.F. Gagel, M.F. Robinson, D.T. Donovan, B.R. Alford, Clinical review 44: medullary thyroid carcinoma: recent progress. J. Clin. Endocrinol. Metab. 76(4), 809–814 (1993)

    Article  PubMed  CAS  Google Scholar 

  24. J.W. de Groot, J.T. Plukker, B.H. Wolffenbuttel, T. Wiggers, W.J. Sluiter, T.P. Links, Determinants of life expectancy in medullary thyroid cancer: age does not matter. Clin. Endocrinol. (Oxf). 65(6), 729–736 (2006). doi:10.1111/j.1365-2265.2006.02659.x

    Article  PubMed  Google Scholar 

  25. D.P. Bradly, V. Reddy, R.A. Prinz, P. Gattuso, Incidental papillary carcinoma in patients treated surgically for benign thyroid diseases. Surgery 146(6), 1099–1104 (2009). doi:10.1016/j.surg.2009.09.025

    Article  PubMed  Google Scholar 

  26. M. Brauckhoff, O. Gimm, R. Hinze, J. Ukkat, K. Brauckhoff, H. Dralle, Papillary thyroid carcinoma in patients with RET proto-oncogene germline mutation. Thyroid 12(7), 557–561 (2002). doi:10.1089/105072502320288393

    Article  PubMed  CAS  Google Scholar 

  27. A.L. Shifrin, J.B. Ogilvie, M.T. Stang, A.M. Fay, Y.H. Kuo, T. Matulewicz, C.Z. Xenachis, J.J. Vernick, Single nucleotide polymorphisms act as modifiers and correlate with the development of medullary and simultaneous medullary/papillary thyroid carcinomas in 2 large, non-related families with the RET V804 M proto-oncogene mutation. Surgery 148(6), 1274–1280 (2010). doi:10.1016/j.surg.2010.09.004. discussion 1280–1271

    Article  PubMed  Google Scholar 

  28. G. Treglia, P. Castaldi, G. Rindi, A. Giordano, V. Rufini, Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine 42(1), 80–87 (2012). doi:10.1007/s12020-012-9631-1

    Article  PubMed  CAS  Google Scholar 

  29. G. Treglia, M.F. Villani, A. Giordano, V. Rufini, Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 fluorodeoxyglucose positron emission tomography: a meta-analysis. Endocrine 42(3), 535–545 (2012). doi:10.1007/s12020-012-9671-6

    Article  PubMed  CAS  Google Scholar 

  30. W.W. Hung, C.S. Wang, K.B. Tsai, F. Ou-Yang, S.J. Shin, P.J. Hsiao, Medullary thyroid carcinoma with poor differentiation and atypical radiographic pattern of metastasis. Pathol. Int. 59(9), 660–663 (2009). doi:10.1111/j.1440-1827.2009.02423.x

    Article  PubMed  Google Scholar 

  31. M. Zabel, J. Grzeszkowiak, Characterisation of thyroid medullary carcinoma TT cell line. Histol. Histopathol. 12(1), 283–289 (1997)

    PubMed  CAS  Google Scholar 

  32. A. Machens, K. Lorenz, H. Dralle, Peak incidence of pheochromocytoma and primary hyperparathyroidism in multiple endocrine neoplasia 2: need for age-adjusted biochemical screening. J. Clin. Endocrinol. Metab. 98(2), E336–E345 (2013). doi:10.1210/jc.2012-3192

    Article  PubMed  CAS  Google Scholar 

  33. D.V. Alapat, K.B. Ain, D.A. Sloan, K.G. Monaghan, R.G. Karabakhtsian, Disparity between tissue and serum calcitonin and carcinoembryonic antigen in a patient with medullary thyroid carcinoma. Endocrine 39(2), 148–152 (2011). doi:10.1007/s12020-010-9433-2

    Article  PubMed  CAS  Google Scholar 

  34. D.R. Clarke, L.A. Smallman, P.H. Rhys-Evans, Triple primary malignant neoplasms in the head and neck. J. R. Soc. Med. 79(11), 676–677 (1986)

    PubMed  CAS  Google Scholar 

  35. T.K. Lee, R.T. Myers, M. Scharyj, R.B. Marshall, Multiple primary malignant tumours (MPMT): study of 68 autopsy cases (1963–1980). J. Am. Geriatr. Soc. 30(12), 744–753 (1982)

    PubMed  CAS  Google Scholar 

  36. T.C. Sandeep, M.W. Strachan, R.M. Reynolds, D.H. Brewster, G. Scelo, E. Pukkala, K. Hemminki, A. Anderson, E. Tracey, S. Friis, M.L. McBride, C. Kee-Seng, V. Pompe-Kirn, E.V. Kliewer, J.M. Tonita, J.G. Jonasson, C. Martos, P. Boffetta, P. Brennan, Second primary cancers in thyroid cancer patients: a multinational record linkage study. J. Clin. Endocrinol. Metab. 91(5), 1819–1825 (2006). doi:10.1210/jc.2005-2009

    Article  PubMed  CAS  Google Scholar 

  37. R.F. Gagel, A.H. Tashjian Jr, T. Cummings, N. Papathanasopoulos, M.M. Kaplan, R.A. DeLellis, H.J. Wolfe, S. Reichlin, The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. N. Engl. J. Med. 318(8), 478–484 (1988). doi:10.1056/NEJM198802253180804

    Article  PubMed  CAS  Google Scholar 

  38. M. Alevizaki, P. Papapetrou, P. Georgouli, C.C. Alevizaki, H. Papadodima, A. Souvatzoglou, D. Koutras, Increased incidence of medullary carcinoma of the thyroid in rural regions in Greece. J. Endocrinol. Investig. 18(3), 220–223 (1995)

    CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that there is no any financial or other potential conflict of interest.

Author information

Authors and Affiliations

  1. Endocrine Unit, Department of Medical Therapeutics, Alexandra Hospital, Athens University School of Medicine, 80, Vas Sofias ave, 11528, Athens, Greece

    Maria Alevizaki, Elena Kyratzoglou & Katerina Saltiki

  2. Oncology Unit, Department of Medical Therapeutics, Alexandra Hospital, Athens University School of Medicine, Athens, Greece

    Aristoteles Bamias & Meletios A. Dimopoulos

  3. Department of Endocrinology, “Evangelismos” Hospital, Athens, Greece

    Marinella Tzanela

Authors
  1. Maria Alevizaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Kyratzoglou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aristoteles Bamias
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marinella Tzanela
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Meletios A. Dimopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Katerina Saltiki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katerina Saltiki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alevizaki, M., Kyratzoglou, E., Bamias, A. et al. Metachronous appearance of second malignancies in medullary thyroid carcinoma (MTC) patients: a diagnostic challenge and brief review of the literature. Endocrine 44, 610–615 (2013). https://doi.org/10.1007/s12020-013-9961-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-013-9961-7

Keywords

Search

Navigation