[Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland]. / Skleroziruyushchii mukoepidermoidnyi rak shchitovidnoi zhelezy s eozinofiliei stromy.

Sclerosing mucoepidermoid carcinoma with stromal eosinophilia of thyroid gland is represented less than 100 cases in the world literature. We present a rare case of sclerosing mucoepidermoid carcinona with stromal eosinophilia in a 69-year-old woman who has been observed for multinodular goiter for more than 3 years. Cytological examination revealed a picture most of all corresponding to a malignant neoplasm (Bethesda V). The patient underwent a thyroidectomy. Pathomorphological examination revealed a neoplasm of mixed structure with foci of cribriform structures and squamous metaplasia with areas of keratinization. According to the IHC study, the expression of TTF-1, p63, cytokeratins 5/6 were positive, while there were no expression of thyroglobulin with its positive reaction in the thyroid tissue. Additional histochemical staining with Alcian blue revealed a positive reaction with a homogeneous acellular substance of the tumor. A comprehensive morphological study with the use of additional stains made it possible to accurately establish the diagnosis, which will determine the further tactics of managing the patient.

[Algorithm for morphological diagnosis of neoplasms in the chiasmal-sellar region]. / Algoritm morfologicheskoi diagnostiki novoobrazovanii khiazmal'no-sellyarnoi oblasti.

In the Turkish saddle area, there is a wide variety of pathological processes, the vast majority of which present as tumors of various origins (up to 90%). For a clear morphological verification of the diagnosis, it is proposed to use a diagnostic algorithm that includes the stages of differential diagnosis of normal adenohypophysis and neurohypophysis with tumors in the anterior and posterior lobes of the pituitary gland, non-pituitary origin neoplasms, as well as with non-tumor pathological processes (inflammation, cystic masses, and hyperplasia). For morphological diagnosis, histochemical and immunohistochemical methods are recommended using various staining techniques (silver impregnation, periodic acid Schiff reaction) of tissue specimens and antibody panels (pituitary hormones, low-molecular cytokeratins, pituitary transcription factors, neuroendocrine markers, etc.).

Somatic Mutations in the BRAF, KRAS, NRAS, EIF1AX, and TERT Genes: Diagnostic Value in Thyroid Neoplasms.

The feasibility of using molecular genetic markers associated with thyroid neoplasms and more aggressive course of the disease is now actively studied. We analyzed the diagnostic value of somatic mutations in the hot spots of BRAF, KRAS, KRAS, EIF1AX, and TERT genes in histological material from 153 patients with thyroid gland neoplasms. BRAF mutations (exon 15, codon area 600-601) were found in 54 patients, NRAS mutations (exon 3, codon 61) were detected in 12 patients; mutations KRAS, TERT, and EIF1AX genes were not detected.

[Limitation of possibilities of cytological diagnosis of papillary thyroid cancer at the pre-surgery stage]. / Ogranichenie vozmozhnostei tsitologicheskoi diagnostiki papillyarnogo raka shchitovidnoi zhelezy na dooperatsionnom etape.

AIM OF STUDY: A comparison of papillary cancer variants diagnosed on the basis of cytological findings of pre-surgery puncture biopsies with a histological variant of papillary cancer. MATERIALS AND METHODS: The findings of two experts specializing in cytological diagnostics of thyroid nodules that diagnosed a possible variant of papillary cancer were compared with histological findings based on the study of material from surgically removed neoplasms. RESULTS: It was shown that the cytological examination at the pre-surgery stage has significant limitations in diagnosing the histological variant of the tumor, despite high sensitivity of method in diagnosing papillary cancer in general. The variability of results of the cytological determination of papillary cancer variant between the two experts was not so significant, it concerned small fluctuations in the frequency of the diagnosing og normal, follicular, cystic and Uortino-like variants. Based on the data of cytological method, it is not possible to establish the encapsulated variant and papillary microcarcinoma; there are limitations in the diagnosis of follicular and high tumor cell variants. CONCLUSIONS: Currently, the advisability of the recommendation to determine the variant of papillary cancer using the cytological method is questionable. However, this does not mean that it is necessary to stop the search for reliable cellular and molecular genetic characteristics of clinically aggressive variants of papillary cancer.

[Thyroid follicular cell tumors: cytohistological comparisons in the context of the new international classification]. / Follikuliarno-kletochnye opukholi shchitovidnoi zhelezy: tsitogistologicheskie sopostavleniia v kontekste novoi mezhdunarodnoi klassifikatsii.

OBJECTIVE: To carry out a correlation retrospective analysis of the histological and cytological findings of follicular cell neoplasms over a two-year period after the publication of the new WHO classification of thyroid tumors (2017), which identifies a category of follicular tumors of uncertain malignant potential (T-UMP). MATERIAL AND METHODS: The investigators of the Clinic, National Medical Research Center for Endocrinology, Ministry of Health of Russia, made a cytohistological comparison of morphological findings, by using the material of surgically removed follicular cell neoplasms. RESULTS: The investigation showed the lack of unreasonably common usage of the histological classification category of T-UMP (3.08%). Non-invasive follicular neoplasm with papillary-like nuclei predominantly diagnosed in the T-UMP category was more frequently (83.3) assigned to Diagnostic Category IV of the 2017 Bethesda system for the cytological diagnosis of thyroid tumors. Cytology showed the highest (98.1%) sensitivity, including classic (97.8%), encapsulated (100%), and follicular (97.7%) options in diagnosing papillary cancer, being substantially inferior in diagnosing follicular and Hürthle cell neoplasms, in which diagnostic category IV category was more frequently established for adenomas (81.4%) and carcinomas (69.5%). CONCLUSION: The morphological differential diagnosis of follicular cell neoplasms seems to be a relevant problem.

[Molecular genetic markers and criteria for the prediction of adrenocortical carcinoma]. / Molekuliarno-geneticheskie markery i kriterii prognoza adrenokortikal'nogo raka.

Studies of the last decade have demonstrated that the morphological and immunophenotypic patterns of adrenocortical carcinoma (ACC) have a high heterogeneity in both the occurrence of various tumors and the development of a solitary tumor. Carcinogenesis of ACC, like most neoplastic processes, is associated with mutations in at least 15 driver genes, with a wide range of chromosomal aberrations, epigenomic changes, and alterations of the microRNA profile. According to the literature, isolated genetic damage is also insufficient for the manifestation of the malignant phenotype of adrenocortical cells. Knudson's two-hit hypothesis is implemented in at least germline mutations: the development of ACC requires a second genetic event occurring in somatic cells, which leads to inactivation of the second allele of the gene. ACC is an extremely heterogeneous disease, which determines the complexity of differential diagnosis with benign adrenocortical tumors and that of prediction of the clinical course. Another no less important issue is the lack of valid predictors for the efficacy of mitotane, the use of which may be associated with severe adverse effects.

[Current criteria for the diagnosis of adrenocortical carcinoma]. / Sovremennye kriterii diagnostiki adrenokortikal'nogo raka.

Adrenocortical carcinoma is a rare malignant tumor of the adrenal cortex with an unfavorable prognosis. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) published the 4th edition of the WHO Classification of Tumors of Endocrine Organs. The updated classification reflects a multidisciplinary experience in diagnosing and predicting the course of adrenal cortex tumors, obtained on the basis of current studies. This paper highlights the key provisions of the updated WHO classification for adrenocortical carcinoma.

[Histopatological and molecular genetic characteristics of clinically aggressive variants of papillary thyroid carcinoma]. / Gistologicheskaia i molekuliarno-geneticheskaia kharakteristika klinicheski agressivnykh variantov papilliarnogo raka shchitovidnoi zhelezy.

Papillary carcinoma is the most commonly diagnosed form of well-differentiated thyroid cancer that is generally characterized by a favorable prognosis. However, a number of relatively rare variants of this tumor, such as papillary carcinoma of high cells, papillary carcinoma of columnar cells, a diffuse sclerosing variant and recently described cancer of shoe nail cell type, are characterized by a less favorable clinical course, a high frequency of distant metastasis, and relatively low overall and relapse-free survival rates. In this connection, it is important to recognize these options at the stage of a primary morphological study. This review of the literature considers the morphological, clinical and molecular genetic features of the above variants of papillary thyroid carcinoma.

[Clinical, morphological, and prognostic features of papillary thyroid carcinoma with different BRAF mutational status assessed by immunohistochemistry]. / Klinicheskie, morfologicheskie i prognosticheskie osobennosti papilliarnogo raka shchitovidnoi zhelezy s razlichnym statusom BRAF, ustanovlennym immunogistokhimicheskim metodom.

The somatic mutation in BRAFT1799A (BRAFV600E), the data on the prognostic role of which are contradictory, is one of the most common molecular genetic abnormalities in the cells of papillary thyroid carcinoma (PTC). OBJECTIVE: To investigate the association of the immunoexpression of mutant BRAF in PTC with different morphological characteristics and long-term treatment results in patients. MATERIAL AND METHODS: Information on inpatients with PTC was obtained from the database of the Pathology Department, A.F. Tsyb Medical Radiology Research Center (a branch of the National Medical Radiology Research Center, Ministry of Health of the Russia). The paraffin-embedded blocks of surgically removed primary, metastatic, and recurrent PTC tissues were cut and stained with hematoxylin and eosin and anti-mutant BRAF monoclonal antibodies. The results of immunohistochemical tests were assessed and the frequency of BRAF immunoexpression was analyzed in relation to various clinical and morphological parameters of tumor growth, the pattern and volume of treatment in the patients, by taking into account its long-term results (the presence or absence of tumor recurrence and metastases in the postoperative period). RESULTS: The expression of mutant BRAF (BRAF+) was noted in 29 (39.3%) of the 74 cases of PTC. The BRAF+ group differed from the BRAF group by a higher proportion of male patients, older age, advanced clinical stage of carcinoma, a predominance of papillary structure of tumors, and a higher frequency of their recurrence and/or metastases in the postoperative period. CONCLUSION: The immunohistochemical assessment of BRAF status opens up a possibility to predict local recurrence and metastases in the postoperative period in patients treated for PTC.

[Pituitary lactotroph adenomas resistant to dopamine agonist treatment: histological and immunohistochemical characteristics]. / Laktotrofnye adenomy gipofiza, rezistentnye k lecheniiu agonistami dofamina: gistologicheskaia i immunogistokhimicheskaia kharakteristika.

OBJECTIVE: To present the histological and immunohistochemical characteristics of pituitary lactotroph adenomas (PLAs) resistant to dopamine agonist treatment. SUBJECT AND METHODS: The investigators examined paraffin-embedded blocks and histological sections obtained from 19 patients (13 women, 6 men), whose median age was 29 (19, 38) years, after surgical treatment (adenomectomy) for PLAs resistant to dopamine agonist treatment. Immunohistological examination was performed using antibodies against prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), type 2 dopamine receptors (DR2), estrogen receptors-α (ERα), the proliferation marker Ki-67, and the endothelial cell marker CD34. RESULTS: The expression of PRL by adenoma cells was revealed in all the patients. The coexpression of PRL and GH without clinical and laboratory signs of acromegaly was established in 3 cases. No expression of TSH, ACTH, LH, or FSH was revealed in any cases. Positive immunoreaction using antibodies against DR2 and ERα was detected in 8 and 6 cases, respectively. No expression of any of the studied receptors was found in 6 patients. Ki-67 was more than 3% in 3 patients and higher in patients with supra- or retrosellar growth. There was a positive correlation between the serum level of Ki-67 and that of PRL at the onset of the disease. There were 37 (25, 85) adenoma vessels, as measured by CD34 immunoexpression. It was ascertained that the patients with parasellar adenoma had more tumor vessels than those without parasellar growth of adenoma and that with the latter invading the cavernous vessels, the number of vessels was statistically significantly more. CONCLUSION: PLAs resistant to dopamine agonists in addition to PRL (100%) can express GH in 16% of cases are characterized by the immunoexpression of DR2 (42%) and ERα (32%), a low proliferative activity, increased angiogenesis in the adenomas with parasellar growth and invasion into the cavernous sinus.

[The new international histological classification of thyroid tumors]. / Novaia mezhdunarodnaia gistologicheskaia klassifikatsiia opukholei shchitovidnoi zhelezy.

The International Agency for Research on Cancer (IARC) published the new 4th Edition of the WHO Classification of Tumors of Endocrine Organs in 2017. As the previous 2004 edition, the new classification gives considerable attention to thyroid neoplasms. The nomenclature of thyroid tumors undergone changes based on the clinical, morphological and molecular genetic findings obtained for the expired period, on respective new views of their malignant potential, and on the prognosis of a number of neoplasms that should be taken into consideration by pathologists in their daily diagnostic practice. The aim of this paper is to present the new Edition of Classification of Thyroid Tumors with an emphasis on the changes made.

[Telomerase reverse transcriptase (TERT) promoter mutations in the tumors of human endocrine organs: Biological and prognostic value].

The analysis of the data available in the literature has shown that telomerase reverse transcriptase TERT promoter may serve as promising markers of malignancy, aggressive disease course, and poor prognosis for malignant tumors of endocrine organs. Considering the established association of mutations with tumors having a poor prognosis (high-grade and anaplastic carcinoma of the thyroid), it is reasonable to perform prognostic-value investigations in a group of low-grade thyroid carcinomas that may occasionally recur and may be resistant to radioactive iodine therapy, i.e. can demonstrate a poor course and prognosis. TERT promoter mutations may be a specific marker of the clinically aggressive forms of adrenocortical carcinoma, but the determination of its diagnostic value calls for additional investigations that will have the larger number cases and establish the association with clinical features and survival rates.

Cells of Benign and Borderline Thyroid Tumor Express Malignancy Markers.

We studied expression of malignancy markers galectin-3, cytokeratin-19, HBME-1, fibronectin, and cyclin D1 in cells of benign (n=51), malignant (n=87), and borderline (n=53) tumors. The results indicate that 3.9% benign and 41.5% borderline tumors express malignancy markers (specificity 98-100%). Follow up over 1-10 years after surgical treatment for borderline tumors showed no progression of tumor growth. We conclude that some benign and borderline tumors represent low-grade neoplasms with favorable prognosis.