OBJECTIVES:To study the predictive role of tumor-associated neutrophils in early luminal HER2-negative breast cancer. MATERIALS AND METHODS:This is a retrospective study conducted on 60 women cases aged from 31 to 79 years underwent surgery for luminal HER2-negative ductal breast cancer in tertiary care cancer centre. We first estimated basic morphological signs: tumor size, tumor grade (by Nottingham Histologic Score), tumor infiltrating lymphocytes (TILs), Lymphovascular invasion, hormonal receptors status, proliferative index, and regional lymph nodes metastasis. The expression of intratumoral neutrophils was studied by CD15 immunohistochemistry which was performed using tissue microarrays. The total number of intratumoral neutrophils, were counted in 5 high-power fields. RESULTS:According to the Nottingham histologic score system, grade I cases were detected in 10 cases (16%), grade II in 34 cases (57%), and grade III in 16 cases (27%). Lymphovascular invasion was determined in 23 cases (38%), and perineural invasion in 14 cases (23%). Number of TILs varied from 0 to 14 (counted in 5 HPF) and averaged 4.2±0.5. Luminal A tumor phenotype was detected in 35 cases (58%), and luminal B HER2-negative in 25 cases (42%). Nineteen (32%) women had metastases in regional lymph nodes (N+). The number of tumor microenvironment neutrophils in luminal HER2-negative breast carcinomas ranged from 1 to 10 (counted in 5 HPF) with an average value of 2.7±0.4. High tumor-associated neutrophils concentration significantly correlated with tumor size (<5mm and >20mm) with p=0.05, high grade (p=0.01), high proliferative index ((r=0.67; p=0.05), TILs (p=0.05), Lymphovascular space invasion (p=0.01)and positive regional lymph nodes metastasis (p=0.001), but not perineural invasion (p=0.1) and also, did not correlate with the expression of estrogen (r=0.18) and progesterone (r=0.14) receptors. CONCLUSION:Tumor-associated neutrophils strongly predict a worse prognosis in early luminal HER2-negative breast cancer.

According to world Health Organization, breast cancer (BC) ranks first among cancer diseases in women in many developed countries of the world and in the Russian Federation. Over the past 20 years, the incidence of breast cancer in the world has increased and continues to increase. This phenomenon dictates the need for a more in-depth molecular biological, genetic and immunological study of the mechanisms of development and progression of this heterogeneous malignant tumor.Recently, there has been increasing interest in the world not on lyin the direct causes of tumor development, but also in factors contributing to its progression, such as the cellular microenvironment of the tumor, the composition of which has a great influence on cancer development, treatment and prognosis. In the cellular microenvironment of the tumor, mononuclear cells are assessed, the proportion of which determines the severity and direction of the immuneresponse. Their importance for choosing the priority type of drug therapy and assessing its effectiveness is shown. The article provide scurrent data on subpopulations of T cells (CD8+, CD4+), B cells (CD20+), and natural killer. Their role in the development and progression of breast cancer is discussed depending on their phenotype. Modern research pays attention to a minor subpopulation of T lymphocytes – TCR-Vδ1+ cells. This subpopulation is represented predominantly in tumor tissue and has an immunosuppressive effect on T-effectors. At the present stage, inflammatory cells – macrophages and neutrophils – are of no less interest. Their role in tumor progression is widely debated. It is known that the differentiation of macrophages into M1 or M2 phenotypes is determined by the tumor microenvironment. The predominance of macrophages with protumor activity promotes tumor progression and cancer metastasis. Additionally, macrophages can stimulate the migration of neutrophils, which, in turn, support the metastasis of breast cancer through the production of matrix metalloproteinases. Matrix metalloproteinase 9 has been reported to promote the formation of vascular endothelial growth factor, which explains the protumor properties of neutrophils. In the context of growing tumor immunotherapy, assessment of tumor microenvironmental factors is promising both in relation to monitoring the effectiveness of breast cancer therapy and in relation to the search for potential therapeutic targets. The review systematizes and summarizes information on this issue to date.

Aim: to study the relationship between clinical and morphological parameters of skin melanoma and the BRAF status of the tumor in patients with stage I of the disease. Materials and methods. The study was retrospective and included 200 patients with stage I skin melanoma (pT1-2aN0M0), of which BRAF status was assessed in 88 patients. All patients underwent clinical data analysis, an extended morphological study and a molecular genetic study to determine the BRAF V600E mutation in the primary tumor. Results. The median age of patients in the total sample was 61.5 years. Mutation in the BRAF V600E gene was detected in 25 patients (28.4%). Patient age, tumor location and Breslow thickness were recognized as independent predictors of BRAF status of stage I skin melanoma. With an increase in the patient's age by 1 year, the chance of having a BRAF V600E mutation decreased by 3.4% or 1.04 times (OR = 0.966; 95% CI = 0.935–0.999; p = 0.045). When melanoma was localized in the lumbar region, the chance of having a BRAF V600E mutation increased by 15.311 times (95% CI = 1.239–189.142; p = 0.033). With a tumor thickness according to Breslow of more than 0.7 mm, the chance of having a BRAF V600E mutation increased by 2.939 times (95% CI = 1.031-8.376; p = 0.044). With a threshold value of the logistic function of 50%, the sensitivity and specificity of the proposed model were 28.0% and 93.7%, respectively. When the threshold function value is reduced to 25.3%, the sensitivity of the model increases to 68% with a simultaneous drop in specificity to 61.9%. Conclusion. Younger age, greater tumor thickness according to Breslow, and tumor localization in the lumbar region in patients with stage I skin melanoma increase the chance of having a BRAF V600E mutation, while other morphological parameters of the tumor are not associated with BRAF status. However, moderate sensitivity does not allow for a sufficiently accurate determination of the presence of a mutation, thereby strengthening the belief in the need for molecular genetic testing.

Inroduction . Polymorbidity significantly increases the risk of complications in the early postoperative period, especially in patients with colorectal cancer, taking into account the initial nutritional status disorder. At present, several scales of postoperative complications risk assessment (POSSUM, RCRI, MUST) are used, but they do not fully meet the needs of modern oncosurgery, so we consider it necessary to compare their effectiveness and propose a new integrated scale. Aim . To establish the most significant factors influencing the outcome of surgical treatment and length of hospitalization in comorbid patients with colon cancer with the development of a surgical risk assessment scale that is most adapted for this group of patients. Materials and methods . We analyzed the data of hospital charts of patients undergo surgery for colorectal cancer in the oncoproctologic department of the S. P. Botkin State Clinical Hospital of the Moscow Healthcare Department in the period from 2019 to 2022. Inclusion criteria: histologically verified colorectal adenocarcinoma; colorectal cancer in stage cT4, cN0, cM0 or cT1–4, cN1–2, cM0; presence of one or more concomitant diseases in the patient. Exclusion criteria: presence of distant metastases of colorectal cancer; absence of confirmed comorbidities; early forms of colorectal cancer (cT1–2, cN0). All patients were assessed for risk of perioperative complications using ASA, POSSUM, MUST, and RCRI scales. The study endpoints were number of days in intensive care, number of days of hospitalization, and 30-day mortality. An Excel database with POSSUM, RCRI, and MUST scale calculators was created for the study. The evaluation of parameters influencing the outcome of hospitalization was performed using ROC analysis and correlation analysis using Pearson’s criterion. To identify the most sensitive parameters affecting the outcome of hospitalization, commonly used calculators were studied in detail. Results . 200 patient records were analyzed. The results of treatment were compared with the data obtained using the postoperative risk scales POSSUM, MUST, RCRI. A comparative analysis of the scales presented above with our proposed integral scale of postoperative complications risk assessment was carried out. It was found that the parameters of our proposed integral scale showed the highest sensitivity (Se >70 %) and specificity (Sp >70 %) to the risk of postoperative complications. Our proposed integral scale showed a moderate correlation with the age of patients (r = 0.475, p = 0.01) and preoperative weight loss (r = 0.592, p = 0.01), as well as a high correlation with POSSUM (r = 0.649, p = 0.01; r = 0.852, p = 0.01) and MUST (r = 0.655, p = 0.01). Conclusion. The developed scale for assessment of surgical risk in comorbid patients with colorectal cancer showed a higher correlation with the outcome of surgical treatment than similar known scales, which indicates its effectiveness and possibility of application in clinical practice after its validation in prospective studies.

This review evaluates the role of the tumor microenvironment of breast cancer focusing on the evidence showing that tumor-associated macrophages, neutrophils, and mast cells directly participate in tumor initiation, proliferation, and metastasizing. This study also describes microenvironment cells pathologic assessment relevant for prognostication and treatment decision. Tumor-associated macrophages stimulate breast tumor progression, including tumor cell growth, invasion and metastasizing. Tumor-associated neutrophils are more prevalent in patients with severe disease or resistance to treatment and it can be explained by their pro-tumor / immunosuppressive characteristics. The contribution of mast cells to tumor development and progression appears to be a controversial area of research. The ability of mast cells to promote angiogenesis is viewed as a key process in promoting tumor development. However, elevated level of mast cells at tumor sites seems to be connected with improved outcomes.

Diffuse midline glioma of the brain is a rare but very aggressive and resistant glial tumor. This pathology is characterized by impossibility of radical surgical treatment, radioresistance, resistance to drug treatment, high morbidity in children, low quality of life of the patients, frequent complications in the form of neurologic deficit, and unfavorable prognosis. The absence of effective treatment scheme for diffuse midline glioma requires identification of other methods (oncolytic virus therapy, immunotherapy) but there is not enough data on this topic leading to the necessity of its further investigation.

Background. Skin melanoma (SM) is a malignant non-epithelial tumor of transformed melanocytes with predominant localization on the skin (more than 90 % of cases). According to statistics for 2021, SM in Russia accounted for 1.82 % of all malignant neoplasms of the adult population and 12.65 % of all skin tumors. There has been a steady and annual increase in the incidence of SM throughout the world, especially in countries with a predominantly Caucasian population. In Russia, over the past 10 years, mortality from SM has increased by 17.6 %. SM is a heterogeneous tumor with a high metastatic potential, because in addition to standard clinical and pathomorphological prognostic factors, the identification of additional factors of progression and unfavorable prognosis of the disease remains an urgent and unresolved problem of modern oncology.Aim. To determine the role of spontaneous tumor regression in the occurrence of SM progression based on the analysis of literature data and their systematization.Results. This literature review reflects various global research data on the role of spontaneous regression of SM in progression. Spontaneous regression of SM is an immunological process in which the disappearance of tumor cells is observed, which leads to the division of the tumor into separate islands with intermediate areas of non-tumor tissue. The mechanism of spontaneous regression of primary SM, as well as its prognostic significance, is not well understood and studied. Of course, most researchers primarily associate the occurrence of spontaneous regression of melanoma with an immune response, since lymphocytic infiltration of the tumor was noted in all cases of regression. The presence of lymphoid infiltration, as well as the quantitative and qualitative ratio of its cells, are important in the development of the tumor process, affect the effectiveness of immunotherapy and is to a greater extent a factor in a favorable prognosis.Conclusion. The prognostic role of spontaneous melanoma regression is still an unresolved and controversial issue. Interestingly, a number of studies demonstrate that regression is an independent predictor of the progression of SM.

Introduction. Melanoma is one of the most aggressive skin tumors, which occurs against the background of malignant transformation and proliferation of melanocytes. Risk factors for the development of cutaneous melanoma are solar radiation and duration of exposure, old age, individual patient characteristics (light skin, a large number of nevi, including atypical ones, family history) and others. Research in recent years shows that this disease is associated with a number of genetic changes, both congenital and acquired.Aim. To study the frequency of occurrence and prognostic significance of the V600E mutation in the BRAF gene in stage I skin melanoma.Materials and methods. The study was retrospective in nature and included 88 patients with stage I cutaneous melanoma (pT1–2aN0M0). All patients underwent a sentinel lymph node biopsy and no metastases were detected in it (pN0). All patients underwent molecular genetic analysis of the tumor to identify the V600E mutation in the BRAF gene with further assessment of the effect on the progression of early skin melanoma in cases of its detection.Results. The median follow-up time for patients was 32.5 (12–214) months. In 25 (28.4 %) patients of the total sample, the V600E mutation in the BRAF gene was detected. Melanoma progression during follow-up occurred in 23.9 % of patients: 44 % with the V600E mutation in the BRAF gene and 15.9 % without it (p = 0.012). In patients with this mutation, regional metastasis was more often observed, with a predominant localization of distant metastases in the bones. Survival rates were significantly higher in patients without a mutation in the BRAF gene: 1-year disease-free survival of patients without a mutation in this gene was 95 %, 3-year – 87%, 5-year – 65 %, in patients with this mutation – 84, 57 and 37 % respectively. According to the results of Cox regression analysis, in the presence of a mutation in the BRAF gene, there was an increase in the risk of progression to stage I cutaneous melanoma by 2.973 times (p = 0.016).Conclusion. The V600E mutation in the BRAF gene occurs in 28.4 % of patients with stage I cutaneous melanoma and is an unfavorable prognostic factor for disease progression.

Skin cancer from sebaceous glands is a rare and aggressive malignant tumor developing from skin appendages. The etiology of this tumor is still unclear and requires further investigation. Furthermore, strict guidelines on management of patients with this pathology have not been formulated. The article presents a clinical case of diagnosis and treatment of skin cancer from sebaceous glands.

Introduction. Merkel’s carcinoma is a neuroendocrine malignant epithelial skin tumor, rapidly progressive, prone to local recurrence and metastasis to regional lymph nodes and internal organs. The etiology and pathogenesis of Merkel’s carcinoma are still an insufficiently studied issue. Because of its rare occurrence, only single observations of Merkel’s carcinoma metastasis without an identified primary focus, most often with regional lymph node involvement, have been described in the world literature.Clinical case. This article presents a clinical case of metastatic lesion of inguinal lymph nodes with microinvasion into femoral artery in Merkel’s carcinoma without identified primary focus. After a comprehensive examination and onco-consilium the patient underwent surgical treatment in the scope of cytoreductive excision of the inguinal lymph node conglomerate on the right side and artery prosthesis with an autovenous graft. According to the routine postoperative pathomorphologic and immunohistochemical studies, the diagnosis of Merkel’s carcinoma metastasis was finally confirmed.Conclusion. Identification and description of such clinical cases are practically significant and can serve for formation of certain algorithms for treatment of Merkel’s carcinoma both with local manifestations and in progressive forms. Patients with Merkel’s carcinoma should be discussed in oncological consiliums, as treatment may include surgical stage, including biopsy of sentinel lymph nodes, adjuvant radiotherapy, chemotherapy and immunotherapy in case of tumor dissemination.

Modern diagnostic methods with more accurate staging of the tumor process and effective high-tech treatment of breast cancer are very relevant, since this disease ranks first in the structure of cancer morbidity and mortality among women. Mapping of the signal lymph node is an alternative to axillary lymphatic dissection in patients with clinically intact regional lymph nodes (cN0). This allows patients to avoid such formidable, often and disabling complications of lymphatic dissection as prolonged postoperative lymphorrhea and lymphatic swelling of the upper extremity (lymphostasis). Radioisotope is the standard method of performing lymph node mapping, but recent years there have been more and more scientific studies and publications on the effectiveness of the non-toxic and non-radioisotope method in oncosurgery – fluorescent lymphography with indocyanine green.This article analyzes the experience and results of performing a mapping signal lymph node by a fluorescent method with indocyanine green at an early staged breast cancer in the Botkin Hospital, Moscow.

Relevance. The study of pigmented melanoma of the skin is an urgent problem today, because this pathology has an aggressive course, frequent localization on the skin, rare occurrence – no more than 2-8% among other malignant neoplasms of the skin, while it is difficult to diagnose clinically, pathohistologically. The purpose of the study: to study the clinical, dermatoscopic and pathomorphological diagnosis of pigmented and pigmented melanoma of the skin. As tasks, the possibilities of diagnosing pigmented and pigmentless melanoma of the skin at the stage of consultation, as well as the features of the use of light microscopy and immunohistochemical examination by pathologists were studied. Material and technical base: Delta Heine 20 dermatoscope, Carl Zeiss Axio Scope A2 light microscope, evaluation of results according to clinical recommendations. As a result of the study, it was revealed that the diagnosis of pigmented, unlike pigmented, melanoma of the skin is difficult due to the lack of characteristic signs. It was concluded that it is advisable to use digital dermatoscopy at the clinical stage; an immunohistochemical examination should be used by a pathologist; if there is doubt about the goodness of the process, an incisional biopsy of the neoplasm with a pathohistological examination is required.

The review covers reduced kidney function in the context of renal cell carcinoma. According to international studies, some patients already have chronic kidney disease at time of disease onset. Surgical treatment leads to a decrease in the total number of functioning nephrons. Drug therapy causes several adverse events including nephrotoxicity. The review discusses the problem of using combination regimens in patients with solitary kidney.

За последние 10 лет произошел существенный прорыв в лечении меланомы кожи, связанный с разработкой и применением таргетных препаратов. Долгое время единственными таргетными препаратами в лечении меланомы кожи являлись BRAF/МЕК и c-KIT-ингибиторы, а также препараты иммунотерапии. Трижды негативные опухоли с отсутствием стандартных мутаций BRAF, NRAS и с-KIT составляют, по разным данным, до 40%. Для этой группы отсутствуют какие-либо эффективные способы лечения после отрицательной динамики на фоне имммунотерапии. Поэтому последние годы ведется активный поиск новых точек приложения лекарственных препаратов в ДНК опухоли, ее белках и микроокружении. Ведутся исследования как драйверных мутаций, так и соматических, обладающих онкогенными свойствами. Однако на данный момент для лечения меланомы с редкими генетическими изменениями FDA (Food and Drug Administration) одобрила только ингибиторы NTRK. В данном обзоре рассмотрены некоторые редкие молекулярно-генетические особенности опухолевых клеток, которые в перспективе могут быть использованы в клинической практике.

Introduction . Cutaneous melanoma is one of the most aggressive malignant tumors, and its nodular form with vertical growth is characterized by unfavorable prognosis. However, in the recent years due to advances in basic oncology, a breakthrough in drug therapy of this pathology was made. To a great extent, it is linked to implementation of new therapy with checkpoint inhibitors. The best and longest response rates of cutaneous melanoma to this treatment were achieved compared to other oncological diseases. This fact can be explained by immunogenicity of cutaneous melanoma, high mutational load, as well as features of its tumor microenvironment, where in most cases high infiltration by immunocompetent cell is observed. However, immune cells vary by their composition and functions. Some of them can even promote tumor growth. Therefore, study of cell composition, degree and distribution of immune infiltration in the tumor can help identify potential factors of favorable and unfavorable prognosis for cutaneous melanoma which is important in clinical practice. Aim . To determine the frequency of CD3 + -, CD4 + -, CD8 + -T-lymphocytes, CD163, BCL6 and SOX10 expression in patients with primary nodular cutaneous melanoma, as well as correlation of these markers with each other and standard morphological parameters for this non-epithelial malignant tumor. Materials and methods. In the study, the expression frequency of CD3 + -, CD4 + -, CD8 + -T-lymphocytes, CD163, BCL6 and SOX10 in the postoperative material of 20 patients with true primary nodular cutaneous melanoma was measured using immunohistological analysis. The correlation of these markers with each other and standard morphological parameters was determined. Results . In most cases of nodular cutaneous melanoma, moderate and marked lymphocytic (immune) infiltration (grade II–III) was observed with no correlation with Breslow tumor thickness. Study of the ratio between CD4-positive T helpers and CD8-positive cytotoxic T lymphocytes in the tumor microenvironment showed that the number of the latter increased the higher was the degree of immune infiltrate. Markedness of macrophage infiltration directly correlated with markedness of lymphocytic infiltration. BCL6 expression in lymphocytes was observed in all cases of infiltration. Conclusion . Immune infiltrate in nodular cutaneous melanoma is a multicomponent, dynamic microenvironment containing both antitumor and tumor-promoting components with balance shifting to one or other side. Their qualitative, quantitative and, possibly, topographic ratios in the primary lesion of cutaneous melanoma affect the effectiveness of drugs and disease prognosis. Knowledge on the predominance of components negatively affecting tumor growth in the primary lesion can help an oncologist in selection of correct treatment tactics and disease observation.

Timely diagnosis and treatment of cutaneous melanoma are important problems as mortality for this pathology exceeds 70 % of all skin tumors, and in Russia this disease is diagnosed at stage I only in 35.7 % of cases. Correctly selected therapy offers good results, but effective treatment requires accurate staging involving detection of metastases in the sentinel lymph nodes which cannot be identified clinically. This review analyzes study data showing the effectiveness of detection of the sentinel lymph nodes using indocyanine green fluorescence method.

Pancreatic cancer (PC) is a malignant highly aggressive tumor that arises and grows under conditions of inflammation and tissue hypoxia. In PC, one of the key processes in progression is epithelial-mesenchymal transition, which leads to early dissemination and rapid realization of metastatic disease, which accounts for low overall survival rates. The tumor, by releasing a wide range of different molecules (circulating DNA, exosomes, proteins and lipids), allows to identify and use them as potential, diagnostic and prognostic biomarkers. This review introduces readers to the liquid biopsy technique. The main applications of the technique in patients with ductal adenocarcinoma of the pancreas are shown. Liquid biopsy is a modern diagnostic method of molecular oncology, the principle of which is to detect circulating tumor cells, DNA, exosomes in biological fluids. Publications evaluating the potential of the method to assess minimal residual disease, evaluate tumor response to systemic therapy, and determine prognosis are discussed. Liquid biopsy is particularly relevant in cases of malignant tumors of difficult localization, in particular, PC. Modern methods of morphological verification of pancreatic tumors (fine needle biopsy under endosonographic control and percutaneous biopsy) have essential disadvantages: low information value, multiple repeated interventions, postmanipulative complications (pancreatitis, bleeding, etc.). Taking into consideration obvious advantages and perspectives of this method over traditional methods of morphological verification, liquid biopsy seems to be a promising diagnostic tool in personalized oncology for pancreatic cancer.