Anna Zelinskaya, Andrey Kvachenyuk, Galina Kulinichenko, Victoria Moroz


Radioiodine refractoriness is the main problem in the diagnosis and treatment of papillary thyroid carcinoma. The aim of the study was to investigate the cytological and immunocytochemical changes of thyrocytes in fine-needle aspiration smears of thyroid papillary cancer metastases in the course of the development of secondary radioiodine resistance. A total of 70 postoperative metastases of thyroid papillary cancer (secondary radioiodine refractory metastases, previously responsive to radioiodine, that eventually loses the ability to radioiodine accumulation, radioiodine-avid metastases, primary radioiodine-refractory metastases), immunohistochemical staining of thyroid peroxidase, thyroglobulin, cytokeratin 17 and cytological analysis were performed. Revealing the presence of specific cellular phenotypes and structures in punctuates, a low percentage of thyroid peroxidase and thyroglobulin-positive thyrocytes allows the development of the method of cytological prediction of the radioiodine therapy effectiveness.


secondary radioiodine refractory metastases; papillary thyroid carcinoma; fine needle aspiration smears; thyroid peroxidase; thyroglobulin

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Bogdanova, T. I., Zurnadzhy, L. Y., Nikiforov, Y. E., Leeman-Neill, R. J., Tronko, M. D., Chanock, S. et. al. (2015). Histopathological features of papillary thyroid carcinomas detected during four screening examinations of a Ukrainian-American cohort. British Journal of Cancer, 113 (11), 1556–1564. doi:

Drozd, V. M., Branovan, I., Shiglik, N., Biko, J., Reiners, C. (2018). Thyroid Cancer Induction: Nitrates as Independent Risk Factors or Risk Modulators after Radiation Exposure, with a Focus on the Chernobyl Accident. European Thyroid Journal, 7 (2), 67–74. doi:

Markovina, S., Grigsby, P. W., Schwarz, J. K., DeWees, T., Moley, J. F., Siegel, B. A., Perkins, S. M. (2014). Treatment Approach, Surveillance, and Outcome of Well-Differentiated Thyroid Cancer in Childhood and Adolescence. Thyroid, 24 (7), 1121–1126. doi:

Haugen, B. R., Alexander, E. K., Bible, K. C., Doherty, G. M., Mandel, S. J., Nikiforov, Y. E. et. al. (2016). 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 26 (1), 1–133. doi:

Busaidy, N. L., Cabanillas, M. E. (2012). Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease. Journal of Thyroid Research, 2012, 1–12. doi:

Pacini, F., Ito, Y., Luster, M., Pitoia, F., Robinson, B., Wirth, L. (2012). Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Review of Endocrinology & Metabolism, 7 (5), 541–554. doi:

Worden, F. (2014). Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Therapeutic Advances in Medical Oncology, 6 (6), 267–279. doi:

Vaisman, F., Carvalho, D. P., Vaisman, M. (2015). A new appraisal of iodine refractory thyroid cancer. Endocrine-Related Cancer, 22 (6), R301–R310. doi:

Deandreis, D., Al Ghuzlan, A., Leboulleux, S., Lacroix, L., Garsi, J. P., Talbot, M. et. al. (2010). Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome? Endocrine Related Cancer, 18 (1), 159–169. doi:

Rivera, M., Ghossein, R. A., Schoder, H., Gomez, D., Larson, S. M., Tuttle, R. M. (2008). Histopathologic characterization of radioactive iodine‐refractory fluorodeoxyglucose‐positron emission tomography‐positive thyroid carcinoma. Cancer, 113 (1), 48–56. doi:

Zelinskaya, A. V. (2019). Cytokeratin 17 and thyroid peroxidase as immunocytochemical markers for reoperative prediction of radioiodine resistance and the effectiveness of radioiodine therapy of papillary thyroid carcinoma. Oncology, 21 (1), 31–35.

Pathology and Genetics of Tumours of Endocrine Organs (2004). WHO Classification of Tumours. IARC Press: Lyon, 320.

Zelinskaya, A. (2019). Immunocytochemical characteristics of thyrocytes in radioiodine refractory metastases of papillary thyroid cancer. Experimental Oncology, 41 (4). doi:

Latza, U., Niedobitek, G., Schwarting, R., Nekarda, H., Stein, H. (1990). Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. Journal of Clinical Pathology, 43 (3), 213–219. doi:

Lastra, R. R., LiVolsi, V. A., Baloch, Z. W. (2014). Aggressive variants of follicular cell-derived thyroid carcinomas: A cytopathologist's perspective. Cancer Cytopathology, 122 (7), 484–503. doi:

Almendro, V., Marusyk, A., Polyak, K. (2013). Cellular Heterogeneity and Molecular Evolution in Cancer. Annual Review of Pathology: Mechanisms of Disease, 8 (1), 277–302. doi:

Studer, H., Gerber, H., Zbaeren, J., Peter, H. J. (1992). Histomorphological and immunohistochemical evidence that human nodular goiters grow by episodic replication of multiple clusters of thyroid follicular cells. The Journal of Clinical Endocrinology & Metabolism, 75 (4), 1151–1158. doi:

Wang, C., Zhang, X., Li, H., Li, X., Lin, Y. (2017). Quantitative thyroglobulin response to radioactive iodine treatment in predicting radioactive iodine-refractory thyroid cancer with pulmonary metastasis. PLOS ONE, 12 (7), e0179664. doi:

Huang, M., Batra, R. K., Kogai, T., Lin, Y. Q., Hershman, J. M., Lichtenstein, A. et. al. (2001). Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non–small cell lung cancer. Cancer Gene Therapy, 8 (8), 612–618. doi:

Ricarte-Filho, J. C., Ryder, M., Chitale, D. A., Rivera, M., Heguy, A., Ladanyi, M. et. al. (2009). Mutational Profile of Advanced Primary and Metastatic Radioactive Iodine-Refractory Thyroid Cancers Reveals Distinct Pathogenetic Roles for BRAF, PIK3CA, and AKT1. Cancer Research, 69(11), 4885–4893. doi:

Liu, Y. Y., Stokkel, M. P., Pereira, A. M., Corssmit, E. P., Morreau, H. A., Romijn, J. A., Smit, J. W. A. (2006). Bexarotene increases uptake of radioiodide in metastases of differentiated thyroid carcinoma. European Journal of Endocrinology, 154 (4), 525–531. doi:

Furuya, F., Shimura, H., Suzuki, H., Taki, K., Ohta, K., Haraguchi, K. et. al. (2004). Histone Deacetylase Inhibitors Restore Radioiodide Uptake and Retention in Poorly Differentiated and Anaplastic Thyroid Cancer Cells by Expression of the Sodium/Iodide Symporter Thyroperoxidase and Thyroglobulin. Endocrinology, 145 (6), 2865–2875. doi:



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