Malignant human thyroid neoplasms associated with blood parasitic (haemosporidian) infection

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Abstract

A retrospective investigation of archival cytology specimens obtained and verified by a fine-needle aspiration biopsy from patients with follicular, papillary, and medullary human thyroid cancers revealed haemosporidian (blood parasitic) infection in thyrocytes (schizogony) and erythrocytes. The exoerythrocytic stage of infection is represented by finding microschizonts. Cytologic material was stained with Romanowsky–Giemsa dye in medical laboratories. Original specimens were stained (re-stained) with Schiff reagent according to the Feulgen method to clarify location of thyrocyte DNA and hemosporidian pathogens, wherein fuchsine was incorporated into DNA molecules after they were hydrolyzed by hydrochloric acid to stain specimens into red-violet color. An intentionally unstained hemosporidian protoplasm during blood parasitic infection was observed as a light band around erythrocyte nuclei. In follicular thyroid cancer, thyrocyte Feulgen staining revealed nuclear DNA and parasitic DNA (haemosporidium nuclei) as punctate inclusions and rings diffusely distributed in the thyrocyte cytoplasm. The thyrocyte cytoplasm and nuclei were vacuolated, with thyrocyte nuclei being deformed, flattened, and displaced to the cell periphery. The erythrocytes contained haemosporidian nuclei (DNA). In papillary thyroid cancer, we were able to localize the nuclear DNA of thyrocytes and the parasitic DNA as punctate inclusions diffusely distributed in the thyrocyte cytoplasm. Two or more polymorphic nuclei may be positioned eccentrically in the hyperplastic cytoplasm. Haemosporidian microschizonts were found circumnuclearly in thyrocytes as well as an exoerythrocytic stage in the blood. In medullary thyroid cancer, the hyperplastic cytoplasm of thyrocytes contained eccentrically located nuclei (DNA) of thyrocytes and small haemosporidian nuclei (DNA), which may occupy the whole thyrocyte. There were thyrocytes with vacuolated cytoplasm and prominent nuclear polymorphism. The size of hyperplastic nuclei was several times larger than that of normal thyrocyte nuclei. The color of stained thyrocyte cytoplasmic and nuclear vacuoles was less red-violet compared with that of surrounding tissues, which potentially indicates the presence of parasitic DNA inside them. The intra-erythrocyte nuclear haemosporidian material of varying sizes in papillary and medullary cancers may evidence about various species and/or pathogen generation. Intracellular parasitism of haemosporidian infection in thyrocytes (schizogony) associated with three thyroid cancer types leads to marked thyrocyte cytoplasmic hyperplasia, cytoplasmic vacuolization, and nuclear vacuolization. Multinucleated thyrocytes with incomplete cytokinesis emerge. Nuclear deformation occurs, which leads to decreased nucleus size, flattening and displacement to the cell periphery, with high risk of DNA mutations and deletions in affected cells, reaching a neoplastic level.

About the authors

Alexander Terletsky

Institute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: terletsky@mcb.nsc.ru

PhD (Biology), Researcher, Laboratory of Molecular Genetics

Russian Federation, Novosibirsk

Larisa G. Akhmerova

Institute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of Sciences

Email: terletsky@mcb.nsc.ru

PhD (Biology), Scientific Secretary
Russian Federation, Novosibirsk

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2. Figure 1. Follicular cancer. The thyrocyte cytoplasm is filled with basophilic inclusions with an area of increased optical density adjacent to the nucleus (schizogony). Vacuoles in the cytoplasm and nucleus. RBCs contain endoglobular inclusions. Romanovsky–Giemsa staining

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3. Figure 2. Follicular cancer. Binuclear thyrocyte with basophilic inclusions in the cytoplasm and nuclei, with two areas of increased optical density (schizogony), vacuoles in the cytoplasm. RBCs contain endoglobular inclusions. Romanovsky–Giemsa staining

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4. Figure 3. Follicular cancer. Cytoadhesive erythrocytes with endoglobular inclusions. Romanovsky–Giemsa staining

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5. Figure 4. Papillary cancer. The cytoplasm of thyrocytes is filled with basophilic inclusions with an area of increased optical density of about 5 μm, located near the thyrocyte nucleus (schizogony). Romanovsky–Giemsa staining

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6. Figure 5. Papillary cancer. Basophilic granularity is found in the thyrocyte cytoplasm and nucleus. Endoglobular inclusions of similar optical density are present in erythrocytes. Romanovsky–Giemsa staining

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7. Figure 6. Papillary cancer. A binuclear thyrocyte with fine basophilic granularity in the cytoplasm and an area of increased nuclear optical density. Incomplete cytokinesis. Romanovsky–Giemsa staining

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8. Figure 7. Papillary cancer. Thyrocyte polymorphic nuclei with vacuoles. A tiny basophilic granularity is observed in the cytoplasm. Areas of increased optical density (schizogony) are closely adjacent to the nuclei. Romanovsky–Giemsa staining

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9. Figure 8. Papillary cancer. Vacuolized and cytoadhesive erythrocytes with endoglobular inclusions. Romanovsky–Giemsa staining

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10. Figure 9. Papillary cancer. Vacuolized and cytoadhesive erythrocytes with large endoglobular inclusions. Romanovsky–Giemsa staining

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11. Figure 10. Papillary cancer. Cytoadhesive erythrocytes with multiple endoglobular inclusions. Romanovsky–Giemsa staining

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12. Figure 11. Papillary cancer. Prominent erythrocyte cytoadhesion with endoglobular inclusions. Romanovsky–Giemsa staining

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13. Figure 12. Medullary carcinoma. Fusiform thyrocytes with polymorphic nuclei, the cytoplasm is filled with small basophilic inclusions. The foci of increased optical density of basophilic granularity are concentrated on one of the thyrocyte poles close to the nucleus. Romanovsky–Giemsa staining

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14. Figure 13. Medullary carcinoma. Thyrocytes with small dusty pinkish granularity in the cytoplasm and an area of increased optical density adjacent to the nucleus (schizogony). Romanovsky–Giemsa staining

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15. Figure 14. Medullary carcinoma. The thyrocyte cytoplasm is filled with fine blue-pink dusty granules. Large basophilic inclusions in the cytoplasm are identical in optical density to erythrocyte endoglobular inclusions. Romanovsky–Giemsa staining

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16. Figure 15. Medullary carcinoma. Thyrocyte polymorphic nuclei and a round haemosporidian microschizont. Romanovsky–Giemsa staining

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17. Figure 16. Medullary carcinoma. Polymorphonuclear thyrocytes with vacuoles in nuclei and cytoplasm. Romanovsky–Giemsa staining

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18. Figure 17. Medullary carcinoma. Binuclear and quadrinuclear thyrocytes with large basophilic granularity in the cytoplasm. Vacuoles in the cytoplasm correspond in size to basophilic inclusions. Romanovsky–Giemsa staining

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19. Figure 18. Medullary carcinoma. Cytoadhesion of erythrocytes with multiple small endoglobular inclusions in erythrocytes. Romanovsky–Giemsa staining

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20. Figure 19. Follicular cancer. Nuclei (DNA) of haemosporidia in hyperplastic thyrocyte cytoplasm and on its nucleus. The thyrocyte nucleus is displaced to the cell periphery. Feulgen staining

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21. Figure 20. Follicular cancer. A spherical thyrocyte with a nucleus displaced to the cell periphery. Nuclei (DNA) of haemosporidia of lilac color in the thyrocyte cytoplasm. Feulgen staining

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22. Figure 21. Follicular cancer. The nuclei (DNA) of thyrocytes are vacuolated, like the cytoplasm, and are displaced to the cell periphery or deformed (compressed). The nuclei (DNA) of haemosporidia are located in the cytoplasm of thyrocytes and erythrocytes. Feulgen staining

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23. Figure 22. Follicular cancer. Small nuclei (DNA) of haemosporidia inside and along the periphery of erythrocytes. Feulgen staining

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24. Figure 23. Follicular cancer. Cytoadhesive erythrocytes with polymorphic nuclei (DNA) of haemosporidia. Feulgen staining

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25. Figure 24. Papillary cancer. Polymorphic nuclei in thyrocytes. Haemosporidian DNA is found as small nucleoli on thyrocyte nuclei and diffusely in the cytoplasm. Feulgen staining

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26. Figure 25. Papillary cancer. Polymorphic nuclei of thyrocytes. At the edges of the groove in the nucleus haemosporidian DNA is found. Haemosporidian microschizonts are located near the nuclei of thyrocytes. Feulgen staining

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27. Figure 26. Papillary cancer. Microschizont — “Koch’ s body” or “pomegranate body” — of haemosporidia among erythrocytes. Polymorphic nuclei (DNA) of haemosporidia in erythrocytes. Feulgen staining

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28. Figure 27. Papillary cancer. Cytoadhesion of blood erythrocytes with polymorphic nuclei (DNA) of haemosporidia, large nuclei of which (6–8 μm), together with their protoplasm, can occupy the entire erythrocyte. Feulgen staining

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29. Figure 28. Papillary cancer. Haemosporidian nuclei are polymorphic. Severe haemosporidian damage to erythrocytes. Feulgen staining

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30. Figure 29. Medullary carcinoma. The nuclei of thyrocytes are vacuolized and located eccentrically in the hyperplastic spherical cytoplasm. The nuclei (DNA) of haemosporidia are contoured or diffusely located in the cytoplasm of the thyrocyte. Feulgen staining

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31. Figure 30. Medullary carcinoma. Thyrocyte vacuolized nucleus and cytoplasm after the development of a haemosporidia infection in it. Feulgen staining

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32. Figure 31. Medullary carcinoma. One- and two-nuclear thyrocytes. The cytoplasm of thyrocytes is filled with haemosporidian DNA in the form of contoured nuclei or diffusely. Feulgen staining

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33. Figure 32. Medullary carcinoma. Hyperplastic nuclei of thyrocytes. In the cytoplasm and on the nuclei, rounded areas of haemosporidian DNA are observed. Feulgen staining

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34. Figure 33. Medullary carcinoma. Vacuolized and cytoadhered erythrocytes with nuclei (DNA) of haemosporidia. Feulgen staining

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Copyright (c) 2023 Terletsky A., Akhmerova L.G.

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