Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI194810.15789/2220-7619-MHT-1948ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИResearch ArticleMalignant human thyroid neoplasms associated with blood parasitic (haemosporidian) infectionЗлокачественные новообразования щитовидной железы человека как следствие кровепаразитарной (гемоспоридийной) инфекцииTerletskyAlexanderТерлецкийАлександр Витальевич
Russian Federation

PhD (Biology), Researcher, Laboratory of Molecular Genetics

к.б.н., научный сотрудник лаборатории молекулярной генетики

terletsky@mcb.nsc.ruAkhmerovaLarisa G.АхмероваЛариса Григорьевна
Russian Federation

PhD (Biology), Scientific Secretary

к.б.н., ученый секретарь

terletsky@mcb.nsc.ruInstitute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of SciencesИнститут молекулярной и клеточной биологии СО РАН13022023240420231322572741605202212022023Copyright ©; 2023, Terletsky A., Akhmerova L.G.Copyright ©; 2023, Терлецкий А.В., Ахмерова Л.Г.2023Terletsky A., Akhmerova L.G.Терлецкий А.В., Ахмерова Л.Г.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/1948

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.

Исследования архивного цитологического материала, полученного врачами-цитологами в ходе выполнения тонкоигольной аспирационной пункционной биопсии при фолликулярном, папиллярном и медуллярном раках щитовидной железы человека, позволили выявить во всех пробах гемоспоридийную (кровепаразитарную) инфекцию в тироцитах (шизогония), эритроцитах и в виде экзоэритроцитарной стадии развития (микрошизонт). Цитологический материал в условиях медицинских лабораторий был окрашен по Романовскому–Гимзе. Для уточнения локализации ядер (ДНК) тироцитов и гемоспоридий было решено окрасить (перекрасить) оригинальные мазки реактивом Шиффа по Фельгену, где краситель фуксин после гидролиза ДНК соляной кислотой встраивается в ДНК и окрашивает ее в красно-фиолетовый цвет. Специально неокрашенная протоплазма гемоспоридий выявлялась в виде светлой полосы вокруг ядер в эритроцитах. При фолликулярном раке щитовидной железы окрашивание по Фельгену позволило локализовать ядра тироцитов (ДНК) и паразитарную ДНК в виде точечных включений, кольцевых форм и диффузно распределенную в цитоплазме тироцита. Цитоплазма и ядра тироцитов вакуолизированы. Ядра тироцитов деформированы, уплощены и смещены к периферии клетки. Эритроциты содержали ядра (ДНК) гемоспоридий. При папиллярном раке щитовидной железы удалось локализовать ядерную ДНК тироцитов и паразитарную ДНК в виде точечных включений, а также диффузно распределенную в цитоплазме тироцитов. В гиперплазированной цитоплазме могут располагаться эксцентрично два и более полиморфные ядра. Микрошизонты гемоспоридий выявлены в тироцитах приядерно, а также в виде экзоэритроцитарной стадии в крови. При медуллярном раке щитовидной железы в гиперплазированной цитоплазме тироцитов удалось локализовать эксцентрично расположенные ядра (ДНК) тироцитов и мелкие ядра (ДНК) гемоспоридий, которые могли заполнять все пространство тироцита. Выявлены тироциты с вакуолизированной цитоплазмой и выраженым полиморфизмом ядер. Размеры гиперплазированных ядер в несколько раз превышали размеры ядер нормальных тироцитов. Вакуоли цитоплазмы и ядер тироцитов окрашивались светлее, чем окружающие ткани (красно-фиолетовым цветом), что, по всей вероятности, свидетельствует о наличии в них паразитарной ДНК. ДНК гемоспоридий в эритроцитах крови при папиллярном и медуллярном раках представлена полиморфными ядрами, что может свидетельствовать об одновременном присутствии в крови разных видов и/или генераций возбудителя. Появляются многоядерные тироциты с незавершенным цитокинезом. Внутриклеточное паразитирование гемоспоридийной инфекции в тироцитах (шизогония) при трех видах рака щитовидной железы приводит к выраженной гиперплазии цитоплазмы, вакуолизации ее и ядра тироцита. Происходит деформация ядер с уменьшением их в размере, уплощением и смещением на периферию клетки, с высокой вероятностью возникновения мутаций и делеций ДНК пораженных клеток, достигающих неопластического уровня.

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