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Compact buds with biphasic differentiation and calcitonin-expressing neuroendocrine cells—previously unrecognized structures of thyroglossal duct unveiled by immunohistochemistry

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Abstract

Immunophenotype of thyroglossal duct (TGD) cysts, including lining epithelium and thyroid remnants, is scarcely addressed in the literature. There is indirect evidence that C cells may be derived from progenitor cells of the midline thyroid primordium. This is supported by the recent concept of the endodermal origin of lateral thyroid anlagen and several case reports. We aimed to search for neuroendocrine cells in TGD cysts and to characterize immunophenotype of the thyroid follicles and epithelial lining of TGD. Out of 98 TGD cysts, 70% contained both cyst-lining epithelium and thyroid follicles, whereas 30% possessed only cyst-lining epithelium. Specimens eligible for immunohistochemistry (n = 61) were stained for thyroid-specific and neuroendocrine markers. Thyroid remnants were positive for thyroid transcription factor 1 (TTF-1) and other thyroid tissue-specific markers and negative for calcitonin. TGD epithelium showed strong p63 positivity. We found that respiratory epithelium in 9.8% of TGDs contained neuroendocrine cells positive for calcitonin, chromogranin A, and synaptophysin but negative for carcinoembryonic antigen. In 44.2% of the cases, we detected compact buds, microscopic structures appearing as nests of epithelial cells with a biphasic population of basal (p63+) and central (TTF-1+) cells. Thyroid remnants in TGD expressed full spectrum of thyroid-specific markers and contained no C cells. Instead, calcitonin-expressing neuroendocrine cells were found among the respiratory epithelium of TGD. These cells can be a potential source of neuroendocrine tumors mimicking medullary carcinoma in median anlage derivatives. We also discovered precursor compact buds with dual immunophenotype and proposed a concept of their morphogenesis.

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References

  1. Allard RH (1982) The thyroglossal cyst. Head Neck Surg 5(2):134–146

    Article  CAS  Google Scholar 

  2. Mondin V, Ferlito A, Muzzi E, Silver CE, Fagan JJ, Devaney KO, Rinaldo A (2008) Thyroglossal duct cyst: personal experience and literature review. Auris Nasus Larynx 35(1):11–25. https://doi.org/10.1016/j.anl.2007.06.001

    Article  PubMed  Google Scholar 

  3. Nilsson M, Fagman H (2013) Mechanisms of thyroid development and dysgenesis: an analysis based on developmental stages and concurrent embryonic anatomy. Curr Top Dev Biol 106:123–170. https://doi.org/10.1016/B978-0-12-416021-7.00004-3

    Article  CAS  PubMed  Google Scholar 

  4. Sugiyama S (1971) The embryology of the human thyroid gland including ultimobranchial body and others related. Ergeb Anat Entwicklungsgesch 44(2):3–111

    CAS  PubMed  Google Scholar 

  5. Katz AD, Hachigian M (1988) Thyroglossal duct cysts. A thirty year experience with emphasis on occurrence in older patients. Am J Surg 155(6):741–744

    Article  CAS  Google Scholar 

  6. Thompson LD, Herrera HB, Lau SK (2016) A clinicopathologic series of 685 thyroglossal duct remnant cysts. Head Neck Pathol 10(4):465–474. https://doi.org/10.1007/s12105-016-0724-7

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ellis PD, van Nostrand AW (1977) The applied anatomy of thyroglossal tract remnants. Laryngoscope 87(5 Pt 1):765–770

    Article  CAS  Google Scholar 

  8. Sprinzl GM, Koebke J, Wimmers-Klick J, Eckel HE, Thumfart WF (2000) Morphology of the human thyroglossal tract: a histologic and macroscopic study in infants and children. Ann Otol Rhinol Laryngol 109(12 Pt 1):1135–1139

    Article  CAS  Google Scholar 

  9. Wei S, LiVolsi VA, Baloch ZW (2015) Pathology of thyroglossal duct: an institutional experience. Endocr Pathol 26(1):75–79. https://doi.org/10.1007/s12022-015-9354-y

    Article  PubMed  Google Scholar 

  10. Kreft A, Hansen T, Kirkpatrick CJ (2005) Thyroid transcription factor 1 expression in cystic lesions of the neck: an immunohistochemical investigation of thyroglossal duct cysts, branchial cleft cysts and metastatic papillary thyroid cancer. Virchows Arch 447(1):9–11. https://doi.org/10.1007/s00428-005-1227-1

    Article  PubMed  Google Scholar 

  11. Ljungberg O (1992) Biopsy pathology of the thyroid and parathyroid. Biopsy pathology series, 1st edn. Chapman & Hall Medical, London, New York

    Google Scholar 

  12. Stein T, Murugan P, Li F, El Hag MI (2018) Can medullary thyroid carcinoma arise in thyroglossal duct cysts? A search for parafollicular C-cells in 41 resected cases. Head Neck Pathol 12(1):71–74. https://doi.org/10.1007/s12105-017-0826-x

    Article  PubMed  Google Scholar 

  13. Yoshida M, Kumamoto H, Ooya K, Mayanagi H (1999) Immunohistochemical study on apoptosis and cell proliferation in the lining epithelium of thyroglossal duct cysts. Oral Med Pathol 4(2):47–54. https://doi.org/10.3353/omp.4.47

    Article  Google Scholar 

  14. Nilsson M, Williams D (2016) On the origin of cells and derivation of thyroid cancer: C cell story revisited. Eur Thyroid J 5(2):79–93. https://doi.org/10.1159/000447333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Burke BA, Johnson D, Gilbert EF, Drut RM, Ludwig J, Wick MR (1987) Thyrocalcitonin-containing cells in the Di George anomaly. Hum Pathol 18(4):355–360

    Article  CAS  Google Scholar 

  16. Palacios J, Gamallo C, Garcia M, Rodriguez JI (1993) Decrease in thyrocalcitonin-containing cells and analysis of other congenital anomalies in 11 patients with DiGeorge anomaly. Am J Med Genet 46(6):641–646. https://doi.org/10.1002/ajmg.1320460608

    Article  CAS  PubMed  Google Scholar 

  17. Pueblitz S, Weinberg AG, Albores-Saavedra J (1993) Thyroid C cells in the DiGeorge anomaly: a quantitative study. Pediatr Pathol 13(4):463–473

    Article  CAS  Google Scholar 

  18. Vandernoot I, Sartelet H, Abu-Khudir R, Chanoine JP, Deladoey J (2012) Evidence for calcitonin-producing cells in human lingual thyroids. J Clin Endocrinol Metab 97(3):951–956. https://doi.org/10.1210/jc.2011-2772

    Article  CAS  PubMed  Google Scholar 

  19. Yaday S, Singh I, Singh J, Aggarwal N (2008) Medullary carcinoma in a lingual thyroid. Singap Med J 49(3):251–253

    CAS  Google Scholar 

  20. Manzoni M, Bono F, Smith A, Cavenaghi G, Garavello W, Pagni F (2016) Thyreoglossal duct cyst with evidence of solid cell nests and atypical thyroid follicles. Endocr Pathol 27(2):175–177. https://doi.org/10.1007/s12022-016-9431-x

    Article  PubMed  Google Scholar 

  21. Bychkov A, Jain D (2018) Multiple sections per slide for immunohistochemistry: a cost-effective alternative for research in resource-limited settings. Anal Quant Cytol Histol 40(4):211–212

    Google Scholar 

  22. Lin F, Shi J, Chen Z, Liu H (2015) Impact of tissue decalcifcation on immunohistochemical detection of select markers for carcinoma of unknown origin. Mod Pathol 28(S2):518A–528A. https://doi.org/10.1038/modpathol.2015.30

    Article  Google Scholar 

  23. Johansson E, Andersson L, Ornros J, Carlsson T, Ingeson-Carlsson C, Liang S, Dahlberg J, Jansson S, Parrillo L, Zoppoli P, Barila GO, Altschuler DL, Padula D, Lickert H, Fagman H, Nilsson M (2015) Revising the embryonic origin of thyroid C cells in mice and humans. Development 142(20):3519–3528. https://doi.org/10.1242/dev.126581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang BY, Gil J, Kaufman D, Gan L, Kohtz DS, Burstein DE (2002) P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Hum Pathol 33(9):921–926

    Article  CAS  Google Scholar 

  25. Preto A, Cameselle-Teijeiro J, Moldes-Boullosa J, Soares P, Cameselle-Teijeiro JF, Silva P, Reis-Filho JS, Reyes-Santias RM, Alfonsin-Barreiro N, Forteza J, Sobrinho-Simoes M (2004) Telomerase expression and proliferative activity suggest a stem cell role for thyroid solid cell nests. Mod Pathol 17(7):819–826. https://doi.org/10.1038/modpathol.3800124

    Article  CAS  PubMed  Google Scholar 

  26. Rios Moreno MJ, Galera-Ruiz H, De Miguel M, Lopez MI, Illanes M, Galera-Davidson H (2011) Immunohistochemical profile of solid cell nest of thyroid gland. Endocr Pathol 22(1):35–39. https://doi.org/10.1007/s12022-010-9145-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gucer H, Mete O (2018) Positivity for GATA3 and TTF-1 (SPT24), and negativity for monoclonal PAX8 expand the biomarker profile of the solid cell nests of the thyroid gland. Endocr Pathol 29(1):49–58. https://doi.org/10.1007/s12022-017-9511-6

    Article  CAS  PubMed  Google Scholar 

  28. Baloch Z, Mete O, Asa SL (2018) Immunohistochemical biomarkers in thyroid pathology. Endocr Pathol 29(2):91–112. https://doi.org/10.1007/s12022-018-9532-9

    Article  CAS  PubMed  Google Scholar 

  29. Nozieres C, Chardon L, Goichot B, Borson-Chazot F, Hervieu V, Chikh K, Lombard-Bohas C, Walter T (2016) Neuroendocrine tumors producing calcitonin: characteristics, prognosis and potential interest of calcitonin monitoring during follow-up. Eur J Endocrinol 174(3):335–341. https://doi.org/10.1530/EJE-15-0917

    Article  CAS  PubMed  Google Scholar 

  30. Larochelle D, Arcand P, Belzile M, Gagnon NB (1979) Ectopic thyroid tissue—a review of the literature. J Otolaryngol 8(6):523–530

    CAS  PubMed  Google Scholar 

  31. Smith JR, Oates E (2004) Radionuclide imaging of the thyroid gland: patterns, pearls, and pitfalls. Clin Nucl Med 29(3):181–193

    Article  Google Scholar 

  32. Barber TW, Cherk MH, Topliss DJ, Serpell JW, Yap KS, Bailey M, Kalff V (2014) The prevalence of thyroglossal tract thyroid tissue on SPECT/CT following (131) I ablation therapy after total thyroidectomy for thyroid cancer. Clin Endocrinol 81(2):266–270. https://doi.org/10.1111/cen.12419

    Article  Google Scholar 

  33. Lee M, Lee YK, Jeon TJ, Chang HS, Kim BW, Lee YS, Park CS, Ryu YH (2015) Frequent visualization of thyroglossal duct remnant on post-ablation 131I-SPECT/CT and its clinical implications. Clin Radiol 70(6):638–643. https://doi.org/10.1016/j.crad.2015.02.018

    Article  CAS  PubMed  Google Scholar 

  34. Abu-Khudir R, Paquette J, Lefort A, Libert F, Chanoine JP, Vassart G, Deladoey J (2010) Transcriptome, methylome and genomic variations analysis of ectopic thyroid glands. PLoS One 5(10):e13420. https://doi.org/10.1371/journal.pone.0013420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Camargo RY, Kanamura CT, Friguglietti CU, Nogueira CR, Iorcansky S, Tincani AJ, Bezerra AK, Brust E, Koyama FC, Camargo AA, Rego FOR, Galante PAF, Medeiros-Neto G, Rubio IGS (2018) Histopathological characterization and whole exome sequencing of ectopic thyroid: fetal architecture in a functional ectopic gland from adult patient. Int J Endocrinol 2018:4682876. https://doi.org/10.1155/2018/4682876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank Otto Ljungberg (Lund University, Sweden) and Paul Scott Thorner (University of Toronto, Canada) for providing access to the rare literature sources and Alyaksandr Nikitski (University of Pittsburg, USA) for the artwork.

Funding

This study received no specific funding.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Somboon Keelawat & Andrey Bychkov

  2. Department of Pathology, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, 296-8602, Japan

    Andrey Bychkov

  3. Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan

    Andrey Bychkov

Authors
  1. Somboon Keelawat
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Contributions

S.K. evaluated samples, analyzed data, and wrote the manuscript.

A.B. conceived and designed the study, evaluated samples, analyzed data, edited the manuscript, and supervised the project.

All authors reviewed the manuscript.

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Correspondence to Andrey Bychkov.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. This study was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University (IRB No. 652/59).

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Supplemental Fig 1

Compact buds and epithelial ribbons in the context of surrounding structures Compact buds lying beneath the epithelial ribbon are not discernible on low power (A). However, immunostaining reveals that the compact buds (yellow arrowhead) produce thyroglobulin (B), in addition to TTF-1 (C) and p63 (D). Epithelial ribbons do not express thyroglobulin (B). Hematoxylin and eosin (A), immunohistochemistry (B–D); ×40; serial sections. (PNG 5320 kb)

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Keelawat, S., Bychkov, A. Compact buds with biphasic differentiation and calcitonin-expressing neuroendocrine cells—previously unrecognized structures of thyroglossal duct unveiled by immunohistochemistry. Virchows Arch 474, 609–617 (2019). https://doi.org/10.1007/s00428-019-02536-6

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