Compact buds with biphasic differentiation and calcitonin-expressing neuroendocrine cells—previously unrecognized structures of thyroglossal duct unveiled by immunohistochemistry
- 19 Downloads
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.
KeywordsThyroglossal 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.
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.
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 was obtained from all individual participants included in the study.
- 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 CrossRefGoogle Scholar
- 4.Sugiyama S (1971) The embryology of the human thyroid gland including ultimobranchial body and others related. Ergeb Anat Entwicklungsgesch 44(2):3–111Google 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 CrossRefGoogle Scholar
- 11.Ljungberg O (1992) Biopsy pathology of the thyroid and parathyroid. Biopsy pathology series, 1st edn. Chapman & Hall Medical, London, New YorkGoogle Scholar
- 19.Yaday S, Singh I, Singh J, Aggarwal N (2008) Medullary carcinoma in a lingual thyroid. Singap Med J 49(3):251–253Google 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):211–212Google 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle Scholar
- 30.Larochelle D, Arcand P, Belzile M, Gagnon NB (1979) Ectopic thyroid tissue—a review of the literature. J Otolaryngol 8(6):523–530Google 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 CrossRefGoogle 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 CrossRefGoogle Scholar