Immunohistochemically detectable thyroglobulin expression in extrathyroidal cancer is 100% specific for thyroidal tumor origin

Thyroglobulin is a secreted 660 kDa glycoprotein produced by thyroid follicular cells used in diagnostic pathology to secure or exclude a thyroidal origin of metastases of unknown primary tumors. This study was performed to estimate specificity of thyroglobulin immunohistochemistry. 9974 tumor sampl...

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Bibliographic Details
Published in:	Annals of diagnostic pathology 2021-10, Vol.54, p.151793-151793, Article 151793
Main Authors:	Steurer, Stefan, Schneider, Jana, Büscheck, Franziska, Luebke, Andreas M., Kluth, Martina, Hube-Magg, Claudia, Hinsch, Andrea, Höflmayer, Doris, Weidemann, Sören, Fraune, Christoph, Möller, Katharina, Menz, Anne, Bernreuther, Christian, Lebok, Patrick, Sauter, Guido, Simon, Ronald, Jacobsen, Frank, Uhlig, Ria, Wilczak, Waldemar, Minner, Sarah, Burandt, Eike, Krech, Rainer H., Dum, David, Krech, Till, Marx, Andreas H., Clauditz, Till S.
Format:	Article
Language:	eng
Subjects:	Carcinoma, Neuroendocrine - metabolism Carcinoma, Neuroendocrine - pathology Female Humans Immunoenzyme Techniques Immunohistochemistry Immunohistochemistry - methods Specificity Thyroglobulin Thyroglobulin - analysis Thyroglobulin - metabolism Thyroid Gland - pathology Thyroid Neoplasms - metabolism Thyroid Neoplasms - pathology Tissue micro array
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Summary:	Thyroglobulin is a secreted 660 kDa glycoprotein produced by thyroid follicular cells used in diagnostic pathology to secure or exclude a thyroidal origin of metastases of unknown primary tumors. This study was performed to estimate specificity of thyroglobulin immunohistochemistry. 9974 tumor samples from 109 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. Thyroglobulin was strongly expressed in all normal thyroid samples but not in any other normal tissues. Thyroglobulin immunostaining was detected in 99.1% of 106 thyroid adenomas, 98.1% of 364 papillary, 95.2% of 147 follicular, and 7.5% of 40 anaplastic thyroid cancers. Twelve of 15 thyroid samples that were thyroglobulin negative on TMAs showed at least a weak focal thyroglobulin positivity in corresponding large sections, suggesting higher sensitivity of large section analysis. Thyroglobulin positivity in one diffuse large B-cell lymphoma of the thyroid, one chondrosarcoma metastasis to the thyroid, and 42.4% of 92 medullary thyroid cancers was considered to be caused by diffusion of thyroidal colloid from destroyed or even intact adjacent follicles. Thyroglobulin positivity was, however, not seen in 6403 extrathyroidal tumors from 104 different tumor types and subtypes. Our data demonstrate a complete specificity of positive thyroglobulin immunostaining for thyroid origin in tumor tissues obtained from extrathyroidal locations. However, for all tumors located within the thyroid, false positivity can occur as a result of tissue contamination by thyroglobulin rich thyroid colloid from adjacent normal tissue. •More than 9,000 tissue samples from 109 different tumor types and 76 non-neoplastic tissues were evaluated.•Thyroglobulin was strongly expressed in all normal thyroid samples but not in any other normal tissue type.•Positive thyroglobulin immunostaining is highly specific for a thyroid origin of tumor cells.
ISSN:	1092-9134 1532-8198