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

  • Somboon Keelawat
  • Andrey BychkovEmail author
Original Article


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.


Thyroglossal duct Thyroglossal duct cyst Immunohistochemistry Calcitonin Neuroendocrine cells 



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.

Authors’ 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.


This study received no specific funding.

Compliance with ethical standards

Conflict of interest

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).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

428_2019_2536_Fig7_ESM.png (5.2 mb)
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)

428_2019_2536_MOESM1_ESM.tif (5.6 mb)
High Resolution Image (TIF 5779 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pathology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  2. 2.Department of Pathology, Kameda Medical CenterChibaJapan
  3. 3.Department of PathologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan

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