Multinucleated Giant Cells’ Incidence, Immune Markers, and Significance: A Study of 172 Cases of Papillary Thyroid Carcinoma

  • Erin BrooksEmail author
  • Linda Simmons-Arnold
  • Shelly Naud
  • Mark F. Evans
  • Abdel Elhosseiny
Original Paper


Multinucleated giant cells (MGCs) are often detected in cases of papillary thyroid carcinoma (PTC). Their origin and significance, however, has not been established. One possibility is that they form in response to injury induced by fine needle aspiration biopsy (FNAB). Other hypotheses are that the chemically-altered colloid produced by PTC induces MGCs to act as colloidophages, or else MGCs are a non-specific immune response ingesting neoplastic follicle cells. We assigned 172 cases of PTC a semi-quantitative score for MGCs. Cases with “many” MGCs were immunohistochemically stained for AEI/AEIII, CD68, and CD163 to assess for epithelial vs histiocytic differentiation, and for thyroglobulin and TTF-1 to assess for MGC ingestion of colloid or thyroid follicle cells respectively. Overall, we identified MGCs in 100/172 (58.1%) PTC specimens; in 45 (26.2%), “many” MGCs were found, while in 55 (31.9%) MGCs were “few.” The mean sizes of PTC in cases with many as opposed to rare/no MGCs was 2.50 cm vs 1.8 [P = 0.003]. The cases of PTC with many MGCs had higher multifocality (26/45 vs 51/127 [P = 0.06]), extrathyroidal extension (21/45 vs 36/127 [P = 0.03]), and recurrence (8/45 vs 9/127 [P = 0.08]), than did cases with rare or no MGCs. The majority of patients both with and without numerous MGCs had previous histories of FNA or hemilobectomy: 40/45 and 99/127 respectively (P = 0.062). The majority of MGCs were positive for CD68 (45/45), CD163 (44/45), thyroglobulin (34/45) and negative for AEI/AEIII (44/45) and TTF-1 (44/45). These results indicate that MGCs in PTC are of histiocytic origin. Cases of PTC with many MGCs have a significantly greater likelihood of extrathyroidal extension and greater tumor size than cases with few/no MGCs. MGCs appear to be functioning largely as colloidophages.


Multinucleated giant cells Papillary thyroid carcinoma Thyroglobulin Colloid 



Portions of this work were presented as a platform at the 97th Annual Meeting of the United States and Canadian Academy of Pathology (USCAP) in Denver, Colorado, March 2008.


  1. 1.
    Guiter G, DeLellis R. Multinucleate giant cells in papillary thyroid carcinoma. A morphologic and immunohistochemical study. Am J Clin Pathol. 1996;106:765–8.PubMedGoogle Scholar
  2. 2.
    Tabbara S, Acoury N, Sidawy M. Multinucleated giant cells in thyroid neoplasms. A cytologic, histologic and immunohistochemical study. Acta Cytol. 1996;40:1184–8.PubMedGoogle Scholar
  3. 3.
    Padberg B, Schroder S. Diagnostic relevance of multinucleated giant cells in papillary thyroid cancer. Pathologe. 2003;24:382–6. doi: 10.1007/s00292-003-0619-8. Article in German.PubMedCrossRefGoogle Scholar
  4. 4.
    Stanta G, Carcangiu M, Rosai J. The biochemical and immunohistochemical profile of thyroid neoplasia. Pathol Annu. 1988;23:129–57.PubMedGoogle Scholar
  5. 5.
    Sinadinovic J, Cvejic D, et al. Altered terminal glycosylation of thyroglobulin in papillary thyroid carcinoma. Exp Clin Endocrinol. 1992;100:124–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Shabb NS, Tawil A, Gergeos F, Saleh M, Azar S. Multinucleated giant cells in fine-needle aspirations of thyroid nodules: their diagnostic significance. Diagn Cytopathol. 1999;21:307–12. doi: 10.1002/(SICI)1097-0339(199911)21:5<307::AID-DC2>3.0.CO;2-1.PubMedCrossRefGoogle Scholar
  7. 7.
    LiVolsi VA. Surgical pathology of the thyroid. Philadelphia: WB Saunders Co; 1990.Google Scholar
  8. 8.
    Al-Brahim N, Asa S. Overview of papillary thyroid carcinoma. Arch Pathol Lab Med. 2006;130:1057–62.PubMedGoogle Scholar
  9. 9.
    LiVolsi V, Albores-Saavedra J, Asa S, et al. Papillary carcinoma. In: DeLellis R, Lloyd R, Heitz P, Eng C, editors. World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of the Endocrine Organs. Lyon, France: IARC Press; 2004. p. 57–66.Google Scholar
  10. 10.
    Tsou PL, Hsiao YL, Chang TC. Multinnucleated giant cells in fine needle aspirations. Can they help differentiate papillary thyroid cancer from benign nodular goiter? Acta Cytol. 2002;46:823–7.PubMedGoogle Scholar

Copyright information

© Humana 2009

Authors and Affiliations

  • Erin Brooks
    • 1
    Email author
  • Linda Simmons-Arnold
    • 2
  • Shelly Naud
    • 3
  • Mark F. Evans
    • 2
  • Abdel Elhosseiny
    • 1
  1. 1.Department of PathologyFletcher Allen Health CareBurlingtonUSA
  2. 2.Division of Experimental PathologyUniversity of VermontBurlingtonUSA
  3. 3.Medical Biostatistics and Bioinformatics FacilityUniversity of VermontBurlingtonUSA

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