[Precancers of the oral mucosa: clinic, diagnostics]. / Predraki slizistoi obolochki rta: klinika i diagnostika.

OBJECTIVE: The aim of the study. Improving the efficiency of diagnosis and detailing the features of the clinic of «potentially malignant¼ diseases of the oral mucosa. MATERIALS AND METHODS: Clinical and laboratory examination of 124 patients of the department of oral mucosa diseases aged 35 to 80 years, among whom there were 75 women and 49 men, with diseases such as erythroplakia - 12 patients, verrucous leukoplakia - 52 patients, erosive form of leukoplakia - 35 patients, cheilitis Manganotti - 25 patients. Histological and immunohistochemical methods of investigation were used as diagnostics. To assess the proliferative activity of epithelial cells, the determination of the Ki-67 index was used. The synthesis of keratin 15 (K15) in epithelial layers was determined as a diagnostic criterion for the severity of neoplasia. The expression of human papillomavirus type 16 (HPV 16) antigens and p16INK4a protein in epithelial cells was studied, as well as the expression of p53 protein. RESULTS: A high prevalence of p53 mutations was observed in patients with erythroplakia. In leukoplakia, the expression of the Ki-67 protein was detected in the cell nuclei in both the basal and parabasal layers of the multilayer squamous epithelium, in 77% of cases, the expression of the p16INK4a protein in the epithelial nuclei with varying degrees of dysplastic changes was noted, and a positive reaction to HPV16 was also observed in the cell nuclei and cytoplasm of epithelial cells in the basal, parabasal and spiny epithelial layers. The appearance of K15 in the cytoplasm of cells above the basal layer with abrasive precancerous cheilitis was found in 48% of cases. CONCLUSION: To diagnose early manifestations of neoplastic processes in «potentially malignant¼ diseases of the oral mucosa, it is necessary to use both classical histological and immunohistochemical methods of investigation with various markers.

[A clinical case of piloleiomyoma]. / Klinicheskii sluchai piloleiomiomy.

The article describes a clinical case of a benign tumor from smooth muscle cells - piloleiomyoma. The incidence of leiomyoma in the skin is 3-5% of all leiomyomas. A 27-year-old patient applied to a medical institution with complaints about an intradermal formation in the ear region that occurred repeatedly within 5 months after surgical treatment. After the first surgical intervention, the patient was consulted in various medical organizations, where the following diagnoses were made: «nodular fasciitis¼, «smooth muscle tumor without signs of malignancy¼ and «non-epithelial spindle cell neoplasm¼. According to ultrasound examination, the formation with dimensions of 11×9×5 mm reached the mastoid process of the temporal bone and was characterized by increased internal blood flow. After surgical removal of the neoplasm, taking into account the difficulties of differential diagnosis, an immunohistochemical study was conducted. An accumulation of smooth muscle cells was detected in the surface layers of the dermis under the epidermis by the immunohistochemical study with the use of the marker SMA. A study on CD34 protein revealed a high density of blood capillaries and the absence of its expression in smooth muscle cells. The proliferative index (Ki-67) and mitotic activity (PHH-3) of cells was also studied. The index of proliferative activity was less than 2%, mitoses were isolated. Thus, the results of immunohistochemical study proved the conclusion of piloleiomyoma.

[Features of molecular genetic diagnosis of verrucous leukoplakia]. / Osobennosti molekulyarno-geneticheskoi diagnostiki verrukoznoi leikoplakii.

OBJECTIVE: To evaluate the initial molecular genetic signs of malignancy of verrucous leukoplakia (VL). MATERIALS AND METHODS: The study of VL was carried out on biopsies of 21 patients with the diagnoses of verrucous hyperplasia (VH) (15 cases - 71.4%) and verrucous carcinoma (VC) (6 cases - 28.5%). Tissue antigens were determined using mouse monoclonal antibodies to the Ki-67 protein (MM1, Diagnostic Biosystems). Telomerase activity was determined using rabbit immunoglobulin (TRT, Abbiotec). The amplification of the TERC (Telomerase RNA Component) portion of the RNA of the third chromosome was studied by the FISH method. RESULTS: In the studied groups, high cell proliferation and significant differences between HC and VC were revealed. The amplification of TERC by the FISH method made it possible to carry out differential diagnostics between VG and VC. According to the results of the study, the amplification of the TERC gene was detected in 100% in VC and in 20% in VG. CONCLUSION: The FISH method makes it possible to detect VL malignancy at an early stage. Amplification of the TERC gene is characteristic of malignant transformation of epithelial cells in VC. In IG, as a rule, there was no amplification, which can serve as evidence of the benign nature of the pathology of COP.

[Molecular and genetic studies of polymorphic adenocarcinoma of the salivary gland: literature review and description of a clinical case]. / Molekulyarno-geneticheskie issledovaniya polimorfnoi adenokartsinomy slyunnoi zhelezy: obzor literatury i opisanie klinicheskogo sluchaya.

The article summarizes the literature data on the results of clinical, histological and molecular genetic studies of polymorphic adenocarcinoma. It is shown that the diagnosis of polymorphic adenocarcinoma presents difficulties due to the variety of morphological structure of its various components, which may correspond to the characteristics of other tumors of the salivary glands, such as pleomorphic adenoma and adenoid cystic carcinoma. Immunohistochemical markers characteristic of this pathology of the salivary glands are described. The article presents a rare clinical case of a male patient with polymorphic adenocarcinoma. Histological examination revealed perineural invasion and a characteristic immunohistochemical profile of tumor cells: low cell proliferative activity for the Ki-67 protein, a positive reaction to antigens: S100, SOX10, P63 and reverse transcriptase TERT. A study conducted by the FISH method revealed the amplification of the TERC gene, which indicates the malignant nature of this neoplasm. Conducting molecular genetic studies is of paramount importance for the diagnosis of polymorphic adenocarcinoma.

[Features of expression of GLUT-1 and Ki-67 proteins in various components of mixed variants of ameloblastoma]. / Osobennosti ekspressii belkov GLUT-1 i Ki-67 v razlichnykh komponentakh smeshannykh variantov ameloblastomy.

THE AIM OF THE STUDY: The aim was to study the metabolic and proliferative activity of the components of ameloblastoma of mixed histological structure. To assess the impact of individual components of mixed variants of ameloblastoma on treatment results and the risk of relapse. MATERIAL AND METHODS: The study included 21 histological specimens of mixed ameloblastoma. To study proliferative and metabolic activity, histological preparations were immunohistochemically stained. To assess the proliferation of tumor components, histological preparations were stained for the presence of antigens to Ki-67, and the level of metabolic activity was assessed by the expression level of the glucose transporter GLUT-1. Statistical analysis was performed using the Mann-Whitney test, statistical significance was determined using the Chi-square test, and correlation analysis was performed using Spearman's. RESULTS: Among the samples of mixed ameloblastoma included in the study, a non-uniform distribution of proliferation and intensity of metabolic activity among the components was obtained. So, among all the components, the plexiform and basal cell variants are distinguished by the greatest proliferative activity. The metabolic activity of these components of mixed ameloblastoma is also increased. CONCLUSIONS: The data obtained allow us to conclude that it is necessary to take into account plexiform and basal cell components of mixed ameloblastoma, as this can affect the effectiveness of treatment and the risk of relapse.

[Optimization of the diagnosis of precancerous diseases of the oral mucosa and lips (Manganotti's abrasive precancerous cheilitis and erythroplakia)]. / Optimizatsiya diagnostiki predrakovykh zabolevanii slizistoi obolochki rta i krasnoi kaimy gub (abrazivnyi prekantseroznyi kheilit Manganotti i eritroplakiya).

OBJECTIVE: To optimize the identification of precancerous diseases of the oral mucosa, such as Manganotti's abrasive precancerous cheilitis and erythroplakia of the oral mucosa using markers Ki-67 and keratin 15. MATERIAL AND METHODS: The study group included 17 patients with Manganotti's abrasive precancerous cheilitis and 8 with erythroplakia of the oral mucosa. A histological analysis was carried out to scrutinize the biopsy material of the oral mucosa of the patients. Ki-67 protein and keratin 15 were used to assess the proliferative activity of epithelial cells and the severity of neoplasia. Results. Thirteen patients with Manganotti's cheilitis had dysplasia of varying degrees, and 4 had signs of malignancy. A high proliferative activity of the Ki-67 protein was found in the stratum basal and stratum spinosum of the epithelium. In 5 patients with erythroplakia, according to histological examination, grade 2-3 intraepithelial neoplasia was revealed and 3 patients had cancer in situ. The expression of keratin 15 in all patients with Manganotti's abrasive precancerous cheilitis and erythroplakia in the basal layer tended to decrease with an increase in the degree of dysplasia, however, the appearance of keratin 15 in the cytoplasm of cells located above the basal layer was discovered. CONCLUSION: The use of Ki-67 protein and keratin 15 as immunohistochemical markers in the study of diseases such as Manganotti's abrasive precancerous cheilitis and erythroplakia of the oral mucosa makes it possible to identify the initial signs of malignancy more accurately in the epithelium.

[Treatment features of odontogenic cystic formations of the mandible using cystotomy]. / Osobennosti lecheniya odontogennykh kistoznykh obrazovanii nizhnei chelyusti metodom tsistotomii.

AIM: The aim of the study was to improve the types of surgical intervention when performing biopsy of large-sized cystic formations of the lower jaw by cystotomy. MATERIAL AND METHODS: 44 patients were examined and surgeries were performed: 12 patients with ameloblastoma, 14 - with keratoxystone tumor, 18 - with dentigerous cyst. All patients had a retained tooth in the cyst cavity. RESULTS: For histological verification of cystic formations of large sized it is necessary to perform cystotomy-typed biopsy with bone tissue and shell fragment collection, using epithelialized flap method. CONCLUSION: Cystotomy-typed biopsy using the method of epithelialized flap can significantly reduce the rehabilitation period and allows to decide on the choice of further method of surgical treatment.

[Organ changes found by postmortem examination in COVID-19 patients]. / Izmeneniya organov, vyyavlennye pri posmertnom issledovanii patsientov s COVID-19.

The postmortem study results presented in 20 sources of literature on 186 COVID-19 patients were analyzed. Pathological changes were noted in multiple organs, by involving predominantly the respiratory, circulatory, and excretory systems. The changes in the lungs were characterized by an increase in organ weight (59.3%), a dark red color of the parenchyma (47.4%), compaction of lung tissue (56%), and signs of lung congestion (37.3%). The histological characteristics found during postmortem lung tissue examination, which were indicative of diffuse alveolar damage, were proliferation of type II alveolocytes in 65.2% of cases, the appearance of hyaline membranes lining the alveoli in 64.4%, and interstitial edema in 54.2%. In the analyzed sources, 22% of cases were noticed to have severe thrombosis and pulmonary artery branch embolism that was associated with lower extremity deep vein thrombosis. In all the sources of literature, acute tubular necrosis, tubular luminal dilatation, and interstitial edema were detected in the kidneys.

[Immunohistochemical diagnosis of necrotizing sialometaplasia]. / Immunogistokhimicheskaya diagnostika nekroticheskoi sialometaplazii.

The article presents a clinical case of an immunohistochemical study of a rare disease: necrotizing sialometaplasia in the hard palate. Due to the complexity of the differential diagnosis between necrotizing sialometaplasia and squamous cell carcinoma, an immunohistochemical method was used with antibodies to proteins Ki-67, P53, P63 and cytokeratins-7 and Immunohistochemical study established low proliferative activity of glandular cells in excretory ducts and metaplastic squamous epithelium for Ki-67 protein, significant expression of protein P63 was detected both in the ductal epithelium nuclei and in metaplastic areas and expression of the mutant protein P53 was approximately absent. Marked expression of cytokeratin-7 in the ducts cells and weak expression in necrotic acini of the glands and metaplastic epithelium was noted. It was shown that cytokeratin-15 homogeneously stains the peripheral zone of metaplastic epithelium, which is characteristic of a benign lesion. Thus, the panel of antibodies to proteins Ki-67, P53 and cytokeratins-7 and 15 allows to verify necrotizing sialometaplasia.

[Immunohistochemical study of Ki-67, p53 and Notch1 expressions in prostate cancer of different grades]. / Immunogistokhimicheskoe issledovanie ekspressii Ki-67, p53 i Notch1 v adenokartsinomakh predstatel'noi zhelezy razlichnoi stepeni zlokachestvennosti.

OBJECTIVE: To determine the prognostic value of the expression of Ki-67, p53, and Notch1 in the diagnosis of prostate cancer. MATERIAL AND METHODS: Surgical and diagnostic materials obtained from patients with benign prostatic hyperplasia, prostate intraepithelial neoplasia, and prostate cancer of different grades underwent studies; a total of 98 patients were examined. Cell antigens were determined using rabbit anti-Ki-67 monoclonal antibodies (Clone SP6), mouse anti-p53 monoclonal antibodies (Clone Y5), and recombinant anti-Notch1 antibodies (Clone EP1238Y). RESULTS: Comparing Ki-67, p53, and Notch1 expression indices revealed statistically significant differences. There was a significant direct correlation between Ki-67 and p53 expression indices and prostate cancer grade groups based on the morphological Gleason grading system (rs=0.736; p<0.001; rs=0.682; p=0.035, respectively) and a strong inverse correlation between Notch1 expression and prostate cancer grade groups (rs= -0.425, p<0.001). CONCLUSION: Notch1 expression in conjunction with the low proliferative activity of cells and the absence of p53 (Y5) protein may suggest that the mechanism of apoptosis is preserved in tumor cells, which expands indications for medical treatment of prostate cancer.

[Immunomorphology of bullous lesions of the oral mucosa]. / Immunomorfologiya puzyrnykh porazhenii slizistoi obolochki rta.

The article is devoted to the study of immunohistochemical parameters in patients with bullous lesions of the oral mucosa. The biopsy samples of the oral mucosa were studied in 57 patients, including patients with pemphigoid bullosa (38 people) and pemphigus vulgaris (19 people). The results of immunohistochemical studies indicate the cellular mechanisms of damage to the epithelium, in which IL-1, IL-6 and HPV16 are involved.

[To the question of proliferative verrucous leukoplakia malignant potential]. / K voprosu o zlokachestvennom potentsiale proliferiruyushchei verrukoznoi leikoplakii.

AIM OF STUDY: To study of neoplastic transformation of the epithelial cells of the oral mucosa with verrucous hyperortokeratosis, verrucous carcinoma and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Oral mucous membrane biopsies of 33 patients with clinical diagnosis of proliferative verrucous leukoplakia were investigated. Histologically in 19 cases (57.6%) was revealed verrucous hyperorthokeratosis, in 8 cases (24.2%) - verrucous carcinoma and in 6 cases (18.2%) - oral squamous cell carcinoma. Tissue antigens were determined using mouse monoclonal antibodies to Ki-67 and mouse monoclonal antibodies to cytokeratin 15. RESULTS OF THE STUDY: In comparison with the proliferative activity of epithelial cells in the malpighian layer in verrucous hyperorthokeratosis (17.2±8.1%) was detected increasingof cell proliferation in epithelial growth zone in verrucous carcinoma (33.8±8.1%) and in peripheral zone of solid areas in oral squamous cell carcinoma (51.2±35.7%). A significant decrease in the expression of cytokeratin 15 in the cytoplasm of tumor cells was noted inverrucous carcinoma and oral squamous cell carcinoma in comparison with verrucous hyperorthokeratosis. CONCLUSION: The obtained results proclaim that there is no stage of epithelial dysplasia during tumor transformation of proliferative verrucous leukoplakia into verrucous carcinoma and oral squamous cell carcinoma. Verrucous carcinoma by the nature of proliferative activity, cell atypia and expression of cytokeratin 15 corresponds to carcinoma in situ.

[Immunohistochemical study of Ki-67, PHH3, and CK15 protein expression in oral epithelial malignancy]. / Immunogistokhimicheskoe issledovanie ékspressii belkov Ki-67, PHH3 i CK15 pri malignizatsii épiteliia slizistoi obolochki rta.

OBJECTIVE: To investigate the expression of Ki-67, phosphohistone H-3 (PHH3), and cytokeratin 15 (CK15) proteins in the cells of the oral mucosa (OM) according to the degree of its malignant transformation. MATERIAL AND METHODS: OM biopsy specimens from 69 patients diagnosed with focal epithelial hyperplasia, intraepithelial squamous cell neoplasia, cancer in situ, and squamous cell carcinoma were examined. Tissue antigens were determined using mouse Ki-67 monoclonal antibodies, rabbit PHH3 polyclonal antibodies, and mouse CK15 monoclonal antibodies. RESULTS: There was an increase in epithelial proliferative and mitotic activities in squamous cell carcinoma and a sharp decrease in the expression of CK15 in the cytoplasm in cancer in situ and squamous cell carcinoma of the OM. CONCLUSION: The protein CK15 can be used for the differential diagnosis between high-grade dysplasia and OM epithelial malignancy at the stage of carcinoma in situ and squamous cell carcinoma.

[Oral manifestations of KID syndrome: rare clinical case]. / Stomatologicheskie proiavleniia KID-sindroma: redkii klinicheskii sluchai.

The paper presents a rare clinical case of an infant with KID (Keratitis, Ichthyosis, Deafness) syndrome (about 100 patients reported so far) admitted for histological verification of oral mucosa lesions. Disease pathogenesis defines inadequate reparation and skin and mucosa innate immunity defect leading to higher incidence of bacterial and fungal infections, so the 4-years old girl received treatment for vegetating candidiasis of the oral mucosa for several weeks with no clinical improvement. Initial examination showed that the oral lesions resulted from sharp edges of severely affected carious teeth. Histological study of multifocal biopsy revealed pyogenic granulomas and no signs of SCC. Teeth extraction and symptomatic treatment leaded to significant clinical improvement and some remained mucosal changes may be attributed to syndrome manifestations.

[Determination of the lesions volume in patients with radionecrosis of the jaws]. / Opredelenie ob''ema porazheniia tkanei cheliustno-litsevoi oblasti u patsientov s osteoradionekrozom cheliustei.

The extent of manifestation of the osteonecrotic process after radiation therapy of malignant neoplasms of the head and neck is currently unknown and little studied. The same can be said about the choice of methods and surgical techniques in this category of patients. We believe that the choice of method is based on the determination of the true size of the defect, the search for the optimal source of complete blood supply as well as the presence of restrictions on the general somatic status. In osteoradionecrosis clinically significant changes occur in the facial vessels, which is reflected both in the bone tissue and in soft tissue structures that correspond not only to irradiation area but also to compromised blood supply area. The study identified histopathological changes in the irradiated vessels, soft tissues and bones of the facial skeleton in 20 of patients. Biopsy findings were correlated with ultrasound and tomographic examination data. Based on the findings summary the methods are proposed for examining patients and choosing the best surgical treatment methods for maximal possible rehabilitation.

[Biocompatibility and osteoinductive properties of collagen and fibronectin hydrogel impregnated with rhBMP-2]. / Biosovmestimost' i osteogennye svoistva kollagen-fibronektinovogo gidrogelya, impregnirovannogo BMP-2.

The study aimed to demonstrate the biocompatibility and osteoinductive properties of a hydrogel based on highly purified collagen and fibronectin impregnated with rhBMP-2. In vitro and in vivo experiments have shown that the minimum effective dosage of rhBMP-2 is 10 µg/ml. The cytocompatibility of the collagen-fibronectin gel was determined using MTT test and staining with PKH-26. There was no inflammation reaction when the material was subcutaneously implanted in rats (n=30) in vivo. The collagen-fibronectin hydrogel containing 10 µg/ml rhBMP-2 showed high osteogenic properties. By the end of 28 days 8±4% of its volume was replaced by newly formed bone tissue in case of subcutaneous implantation, 17±10% in intramuscular implantation and 26±11% in intraosseous implantation in the calvarial critical-size. The optimal combination of biocompatible and osteogenic properties of collagen-fibronectin hydrogel impregnated with BMP-2 allows us to consider it as a promising basis for creating the new generation of osteoplastic materials for dentistry.

[Cytokeratin 15 as a diagnostic marker for oral epithelial malignization]. / Tsitokeratin 15 kak diagnosticheskii marker nachala malignizatsii épiteliia slizistoi obolochki rta.

The paper presents an example of an immunohistochemical study of malignancy in oral epithelial hyperplasia. In the described case in view of the difficulty in determining the onset of the epithelial malignancy with the usual histological technique, an immunohistochemical method was used with antibodies to proteins Ki-67, human papillomavirus (HPV) type 16 and cytokeratin 15. The results of immunohistochemical study indicated increased proliferative activity of epithelial cells, presence of papillomavirus HPV16 in their cytoplasm and synthesis of cytokeratin 15 in all layers of the epithelium. These characteristics of squamous intraepithelial neoplasia may be a diagnostic criterion for the beginning of oral epithelial malignization.

[The role of Sonic Hedgehog signaling pathway in the development of oral squamous cell carcinoma]. / Rol' signal'nogo puti Sonic Hedgehog v formirovanii ploskokletochnogo raka slizistoi obolochki rta.

The research of the Sonic Hedgehog signaling pathway activity was carried out on biopsy specimens of 43 patients with oral hyperplasia, squamous intraepithelial neoplasia and oral squamous cell carcinoma. Tissue antigens were determined using a mouse monoclonal antibody to Ki-67 protein and rabbit monoclonal antibody to Gli-1 protein. In squamous intraepithelial neoplasia and oral squamous cell carcinoma specimens Gli-1 was detected in the cytoplasm of cells only. The correlation was found between the proliferative activity of epithelial cells and Gli-1 distribution. Protein Gli-1 can be used for early diagnosis of malignant transformation of oral stratified squamous epithelium.

[The role of Wnt/ß-catenin signaling pathway in ameloblastoma formation]. / Rol' Wnt/ß-kateninsignal'nogo puti v formirovanii ameloblastomy.

The aim of the study was to assess the role of the canonical Wnt/ß-catenin signaling pathway in the formation and clinical course of various histological variants of ameloblastoma. MATERIAL AND METHODS: 76 cases of ameloblastoma were investigated, the average age of the patients was 46 years. There were 49 (64.5%) cases of recurrence of the disease. Tissue antigens were determined using monoclonal rabbit antibodies to Ki-67 and ß-catenin. RESULTS: it was found correlation between the proliferative activity of ameloblastoma cells and the intranuclear localization of ß-catenin, indicating the activation of the Wnt/ß-catenin-signaling pathway. It was shown that the nuclear localization of ß-catenin is positively correlated with the recurrence. CONCLUSION: The Wnt/ß-catenin signaling pathway is involved in a formation and progression of ameloblastoma.

[The proliferative activity of tumor cells and the distribution of SOX2+ pluripotent stem cells in various histological types of ameloblastoma]. / Proliferativnaia aktivnost' kletok opukholi i raspredelenie SOX2+ pliuripotentnykh stvolovykh kletok v razlichnykh gistologicheskikh variantakh ameloblastomy.

AIM: to investigate the proliferative activity and distribution of pluripotent stem cells in various histological types of amelobrastoma. MATERIAL AND METHODS: The surgical and archival materials of 76 patients with ameloblastoma from the Central Research Institute of Dentistry and Oral Surgery, Ministry of Health of the Russian Federation, were used. Tissue antigens were determined using a rabbit monoclonal antibody against to Ki-67 and SOX2. RESULTS: Proliferating (Ki-67) and pluripotent (SOX2) cells were identified in various histological types of ameloblastoma. A weak significant correlation was found between tumor size, pluripotent stem cells, and cellular proliferative activity. Enhanced cell proliferative activity and extensive bone tissue destruction significantly correlated with the development of recurrent ameloblastoma. CONCLUSION: The presence of pluripotent stem cells, the proliferative activity of ameloblastoma cells, and the extensiveness of bone tissue destruction allow basal-cell and plexiform options to be considered as the most aggressive indicators.