Surgery Today

, Volume 29, Issue 11, pp 1189–1194 | Cite as

Dedifferentiation of neoplastic cells in medullary thyroid carcinoma: Report of a case

  • Michitoshi Osaka
  • Jun Soga
  • Youichi Tamiya
  • Tsutomu Suzuki
Case Reports


We report herein the unusual case of a man who was diagnosed as having sporadic medullary thyroid carcinoma (MTC) at the age of 29 years, and subsequently followed up for a period of 18 years. A total thyroidectomy with radical neck dissection was initially performed, followed by a stable interval of 16 years with regional metastases. He then developed widely disseminated metastases resulting in death within 2 years at the age of 47 years. While the neoplastic tissue from localized metastases in the soft tissue of the neck expressed strong immunohistochemical positivity to calcitonin (CT), calcitonin gene-related peptide, carcinoembryonic antigen, neuron-specific enolase, and chromogranin A during the stable interval, extremely weakened immunoreactivity to those markers was observed in samples from the disseminated metastases in the subcutaneous tissue after his clinical deterioration. Furthermore, only a few neoplastic cells in specimens obtained at postmortem sampling exhibited a weak response to CT. Ultrastructurally, the characteristic secretory granules in the neoplastic cells decreased remarkably in number, consistent with the immunohistochemical findings. These granules also diminished in diameter and intracytoplasmic small lumina and intercellular clefts with microvilli, interpreted as an attribute of anaplastic thyroid carcinomas, were frequently observed in tissues obtained after his clinical deterioration or at postmortem sampling. These cytological changes might represent dedifferentiation of the neoplastic cells or the anaplastic transformation of MTC.

Key Words

medullary thyroid carcinoma dedifferentiation calcitonin immunohistochemistry ultrastructure 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hazard JB, Hawk WA, Crile G Jr (1959) Medullary (solid) carcinoma of the thyroid. A clinicopathologic entity. J Clin Endocrinol Metab 19:152–161CrossRefPubMedGoogle Scholar
  2. 2.
    Saad MF, Ordóñez NG, Rashid RK, Guido JJ, Hill CS Jr, Hickey RC, Samaan NA (1984) Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 63:319–342Google Scholar
  3. 3.
    Nishiyama RH, Dunn EL, Thompson NW (1972) Anaplastic spindle-cell and giant-cell tumors of the thyroid gland. Cancer 30:113–127CrossRefPubMedGoogle Scholar
  4. 4.
    Zeman V, Němec J, Platil A, Zamrazil V, Pohunková D, Neradilová M (1978) Anaplastic transformation of medullary thyroid cancer. Neoplasma 25:249–255PubMedGoogle Scholar
  5. 5.
    Kakudo K, Miyauchi A, Ogihara T, Takai S, Kitamura H, Kosaki G, Kumahara Y (1978) Medullary carcinoma of the thyroid. Giant cell type. Arch Pathol Lab Med 102:445–447PubMedGoogle Scholar
  6. 6.
    Bussolati G, Monga G (1979) Medullary carcinoma of the thyroid with atypical patterns. Cancer 44:1769–1777CrossRefPubMedGoogle Scholar
  7. 7.
    Mendelsohn G, Baylin SB, Bigner SH, Wells SA Jr, Eggleston JC (1980) Anaplastic variants of medullary thyroid carcinoma. A light-microscopic and immunohistochemical study. Am J Surg Pathol 4:333–341CrossRefPubMedGoogle Scholar
  8. 8.
    Nieuwenhuijzen Kruseman AC, Bosman FT, van Bergen Henegouw JC, Cramer-Knijnenburg G, Brutel de la Riviere G (1982) Medullary differentiation of anaplastic thyroid carcinoma. Am J Clin Pathol 77:541–547PubMedGoogle Scholar
  9. 9.
    Martinelli G, Bazzocchi F, Govoni E, Santini D (1983) Anaplastic type of medullary thyroid carcinoma. An ultrastructural and immunohistochemical study. Virchows Arch A 400:61–67CrossRefGoogle Scholar
  10. 10.
    Nesland JM, Holm R, Sund BS, Johannessen JV (1986) A thyroid tumor in a 57-year-old man. Ultrastruct Pathol 10:197–202CrossRefPubMedGoogle Scholar
  11. 11.
    Kakudo K, Miyauchi A, Katayama S, Watanabe K (1987) Ultrastructural study of poorly differentiated medullary carcinoma of the thyroid. Virchows Arch 410:455–460CrossRefGoogle Scholar
  12. 12.
    Baschieri I, Ronga G, Fiorentino A, Mariani P, Carlei F (1990) Thyroid carcinoma with biphasic clinical course and evolution in medullary carcinoma-follicular variant. A case report and an immunocytochemical demonstration of calcitonin and thyroglobulin in the same neoplastic cells. J Nucl Med Allied Sci 34:71–76PubMedGoogle Scholar
  13. 13.
    Hill CS Jr, Ibanez ML, Samaan NA, Ahearn MJ, Clark RL (1973) Medullary (solid) carcinoma of the thyroid gland: an analysis of the M.D. Anderson Hospital experience with patients with the tumor, its special features, and its histogenesis. Medicine (Baltimore) 52:141–171Google Scholar
  14. 14.
    Williams ED (1966) Histogenesis of medullary carcinoma of the thyroid. J Clin Pathol 19:114–118CrossRefPubMedGoogle Scholar
  15. 15.
    Saad MF, Ordóñez NG, Guido JJ, Samaan NA (1984) The prognostic value of calcitonin immunostaining in medullary carcinoma of the thyroid. J Clin Endocrinol Metab 59:850–856CrossRefPubMedGoogle Scholar
  16. 16.
    Lippman SM, Mendelsohn G, Trump DL, Wells SA Jr, Baylin SB (1982) The prognostic and biological significance of cellular heterogeneity in medullary thyroid carcinoma: a study of calcitonin, L-dopa decarboxylase and histaminase. J Clin Endocrinol Metab 54:233–240CrossRefPubMedGoogle Scholar
  17. 17.
    Ruppert JM, Eggleston JC, deBustros A, Baylin SB (1986) Disseminated calcitonin-poor medullary thyroid carcinoma in a patient with calcitonin-rich primary tumor. Am J Surg Pathol 10:513–518CrossRefPubMedGoogle Scholar
  18. 18.
    Capella C, Bordi C, Monga G, Buffa R, Fontana P, Bonfanti S, Bussolati G, Solcia E (1978) Multiple endocrine cell types in thyroid medullary carcinoma. Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells. Virchows Arch A 377:111–128Google Scholar
  19. 19.
    Sikri KL, Varndell IM, Hamid QA, Wilson BS, Kameya T, Ponder BAJ, Lloyd RV, Bloom SR, Polak JM (1985) Medullary carcinoma of the thyroid. An immunocytochemical and histochemical study of 25 cases using eight separate markers. Cancer 56:2481–2491CrossRefPubMedGoogle Scholar
  20. 20.
    Saad MF, Fritsche HA Jr, Samaan NA (1984) Diagnostic and prognostic values of carcinoembryonic antigen in medullary carcinoma of the thyroid. J Clin Endocrinol Metab 58:889–894CrossRefPubMedGoogle Scholar
  21. 21.
    Miyauchi A, Onishi T, Morimoto S, Takai S, Matsuzuka F, Kuma K, Maeda M, Kumahara Y (1984) Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann Surg 199:461–466CrossRefPubMedGoogle Scholar
  22. 22.
    Takami H, Ito K (1992) Calcitonin gene-related peptide as a tumor marker for medullary thyroid carcinoma. Int Surg 77:181–185PubMedGoogle Scholar
  23. 23.
    Chan AS, Conen PE (1971) Ultrastructural observation on cytodifferentiation of parafollicular cells in the human fetal thyroid. Lab Invest 25:249–259PubMedGoogle Scholar
  24. 24.
    Roediger WEW (1973) A comparative study of the normal human neonatal and the canine thyroid C cell. J Anat 115:255–276PubMedGoogle Scholar
  25. 25.
    Kakudo K, Miyauchi A, Katayama S (1977) Ultrastructural study of thyroid medullary carcinoma. Acta Pathol Jpn 27:605–622PubMedGoogle Scholar
  26. 26.
    Johannessen JV, Gould VE, Jao W (1978) The fine structure of human thyroid cancer. Hum Pathol 9:385–400CrossRefPubMedGoogle Scholar
  27. 27.
    Lampertico P (1993) Anaplastic (sarcomatoid) carcinoma of the thyroid gland. Semin Diagn Pathol 10:159–168PubMedGoogle Scholar
  28. 28.
    Sobrinho-Simões MA, Nesland JM, Holm R, Johannessen JV (1985) Transmission electron microscopy and immunocytochemistry in the diagnosis of thyroid tumors. Ultrastruct Pathol 9:255–275CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • Michitoshi Osaka
    • 1
  • Jun Soga
    • 2
  • Youichi Tamiya
    • 3
  • Tsutomu Suzuki
    • 3
  1. 1.Niigata Red Cross Blood CenterNiigataJapan
  2. 2.College of Biomedical TechnologyNiigata UniversityNiigataJapan
  3. 3.First Department of Surgery, School of MedicineNiigata UniversityNiigataJapan

Personalised recommendations