Arkhiv patologii最新文献

Pathomorphological changes in preeclampsia develop in all elements of the functional system "mother-placenta-fetus" and play a leading role in the course and outcome of pregnancy.

Objective: To identify morphological markers of mitochondrial dysfunction of the basal plate cytotrophoblast of the placenta in women with preeclampsia of varying severity.

Material and methods: Comprehensive morphological examination of placentas from women with uncomplicated pregnancy (30), moderate (30) and severe (30) preeclampsia included overview histology, morphometry, immunohistochemistry and transmission electron microscopy.

Results: Regardless of the severity of preeclampsia, a leading place in the pathomorphological change in the placenta is occupied by a violation of uteroplacental circulation due to a violation of cytotrophoblast invasion. Immunohistochemical parameters of mitochondrial dysfunction of cytotrophoblast cells of the basal lamina have been determined. A significant decrease in the expression of mtDNA transcription and replication proteins (TFAM, POLG) and a violation of the structure of the respiratory chain (NADH+, cytochrome C) were revealed. These changes were combined with ultrastructural rearrangement of mitochondria, which are the basis of ATP synthesis. In moderate preeclampsia, a decrease in the number of mitochondria was revealed, the ratio of oval and rounded forms of mitochondria associated with swelling of the central parts of the crist changes. In severe preeclampsia, the structural basis of the connection of energy metabolism between mitochondria and the granular endoplasmic reticulum is interrupted. The progressive destruction of mitochondrial crysts with the formation of pseudovesicles ends with total necrosis of ultrastructures.

Conclusion: In pregnant women with preeclampsia, mitochondrial dysfunction of the cytotrophoblast cells of the basal lamina was diagnosed, characterized by a decrease in the expression of mtDNA transcription and replication proteins in combination with a violation of the I-III enzymatic complexes of the respiratory chain. The identified immunohistochemical markers are pathogenetically associated with ultrastructural rearrangement of mitochondria in preeclampsia of varying severity.

Disorders of sex development or hermaphroditism are a condition associated with a discrepancy between genetic, gonadal, and phenotypic sex. Persistent Müllerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism. Typical features are cryptorchidism and the presence of underdeveloped fallopian tubes, uterus or upper vagina in a male with karyotype 46, XY. Over the past 50 years, about 200 cases of persistent Müllerian duct syndrome have been reported. The article describes an observation of a 33-year-old patient with bilateral cryptorchidism, testicular neoplasm, and false hermaphroditism revealed during the examination of surgical material. Macroscopic and microscopic pictures are presented, including those using immunohistochemical methods. The results of a molecular genetic study of the surgical material are given. After all the examinations, the patient was diagnosed with: Typical seminoma of the right undescended testicle, pT2. False hermaphroditism.

Objective: To evaluate the impact of combined anti-PD-1 immunotherapy on the cellular composition of the tumor microenvironment in patients with gastric cancer.

Material and methods: The study included 9 patients with morphologically confirmed gastric adenocarcinoma (stages T2-4N0-1M0) and positive PD-L1 status (CPS >1). All patients received 8 courses of preoperative chemotherapy according to the FLOT regimen, combined with additional immunotherapy using pembrolizumab (400 mg every 6 weeks). Changes in the tumor microenvironment were assessed using multicolor immunofluorescence followed by quantitative analysis of the proportions of CD8⁺ cytotoxic T-lymphocytes, CD20⁺ B-lymphocytes, CD163⁺ macrophages, and FoxP3⁺ regulatory T-cells.

Results: A statistically significant increase in the number of CD8⁺ T-lymphocytes (from 3.18% to 6.23%, p=0.0391) and, in particular, their PD-1-expressing subpopulation (from 0.00% to 0.22%, p=0.0156) was observed, while the numbers of CD20⁺, CD163⁺, and FoxP3⁺ cells remained unchanged. As a result, the CD8⁺/FoxP3⁺ cell ratio significantly increased during combined anti-PD-1 immunotherapy (from 0.69 to 3.22, p=0.0039). Additionally, associations were identified between immune parameters and clinicopathological characteristics, suggesting that gender and tumor stage may influence the immune response.

Conclusion: The obtained data indicate a remodeling of the tumor microenvironment under the influence of anti-PD-1 therapy, which potentially enhances the antitumor immune response and opens prospects for further optimization of gastric cancer treatment.

Neuroendocrine neoplasms (NENs) are heterogeneous tumors with a common phenotype. There are two fundamentally different groups of NENs: well differentiated with a low proliferative index, called neuroendocrine tumors (NETs) and poorly differentiated with a high proliferative index, called neuroendocrine carcinoma (NEC). Extrahepatic bile duct NETs (EBNETs) account for 0.2% to 2% of all gastrointestinal NETs and up to 2% of all malignant neoplasms of the extrahepatic bile ducts. To date, 114 cases of EBNETs have been described, with disease-free survival ranging from 2 to 240 months. In most cases, the tumors expressed Chromogranin A, Synaptophysin, CD56, and NSE. This report presents a rare case of an EBNET in a 61-year-old patient following resection of the extrahepatic bile ducts. The description includes data from radiological and ultrasound diagnostic methods, macro- and microscopic characteristics of the tumor, and immunohistochemical profile.

Germ cell tumors are rare testicular neoplasms that occur in young men, and their proportion is 2%. Pathological changes in the immune landscape of seminoma - the interaction of mast cells, T-, B-lymphocytes and macrophages with atypical spermatogenic cells, possibly impart a certain uniqueness to seminoma, and their number determines the stage of tumor growth. At the same time, the question of the participation of mast cells in the progression of seminoma remains debatable.

Objective: Immunophenotypic analysis of mast cells in non-metastatic seminoma.

Material and methods: According to anamnestic and clinical-morphological data, the following groups were formed: Group I (n=73; age 20-53 years) - seminomas, according to the pTNM classification: subgroup Ia - T1N0M0 (n=31); Ib subgroup - T2N0M0 (n=42). II group - comparison (n=21, age 20-53 years) - intact testicles. Histochemical (Toluidine blue) and immunohistochemical (antibodies to Tryptase, Chymase and CPA3) research methods were used.

Results: Based on the conducted histochemical reactions, it was found that mature mast cells predominate in seminoma, and their number is directly proportional to the pTNM stage. In immunohistochemical analysis of mast cells, we also observed a quantitative change in specific proteases, especially Tryptase, depending on the pTNM stage of seminoma, towards their decrease.

Conclusion: Immunophenotypic distribution of secretome granules indicates a decrease in the number of Tryptase-, Chymase- and CPA3-mast cells, which is inversely proportional to the pTNM stage of non-metastatic seminoma.

Undifferentiated small round cell sarcoma of bone and soft tissue are rare, malignant neoplasms, often presenting diagnostic challenges due to its overlapping features with other conditions such as osteomyelitis and Brodie abscess. Accurate diagnosis requires a combination of imaging studies, histopathology, and genetic testing. Delayed or misdiagnosis can impact the prognosis and treatment outcomes. We present the case of a 34-year-old female who initially presented with persistent left upper thigh pain. Initial imaging raised suspicion of chronic osteomyelitis, with subsequent MRIs showing abnormal bone marrow edema and a lytic lesion in the left femoral diaphysis. Despite undergoing multiple biopsies, results remained inconclusive, with differential diagnoses including Brodie's abscess. The patient experienced temporary improvement, but her symptoms recurred, prompting further investigations. A repeat MRI showed the progression of intramedullary lesions and the appearance of new focal lesions. A biopsy eventually confirmed the presence of a malignant round cell tumor, identified as Ewing sarcoma through immunohistochemical evaluation and detection of EWSR1 gene rearrangement on FISH analysis and further NGS confirming EWSR1-NFATC2 fusion, diagnostic of the rare entity - round cell sarcoma with EWSR1-NFATC2 fusion. This case highlights the diagnostic complexities of round cell sarcoma of bone, which can mimic other benign bone lesions. It underscores the importance of multidisciplinary evaluation, genetic testing, and timely oncological intervention to improve patient outcomes.

Neuroblastoma is a disease characterized by clinical, histological and genetic heterogeneity. The morphological type, immunohistochemical expression of proteins (MYCN, MYC) and molecular genetic characteristics of the tumor (the status of the MYCN gene and chromosomal regions 1p and 11q) are key to predicting the course of the disease and choosing therapy.

Objective: Estimate the prevalence of the most clinically significant genetic events in different histological groups and among neuroblastomas in general and to demonstrate rarer genetic findings.

Material and methods: A total of 233 cases of patients with neuroblastoma, for whom the histological conclusion and the results of cytogenetic examination by FISH (the status of the MYCN gene and chromosomal regions 1p and 11q) were known, were analyzed. Based on these data, the cases were divided into favorable and unfavorable histological groups, in each of which the presence of genetic abnormalities was analyzed. Also, 28 cases of patients with large cell neuroblastoma were analyzed, for whom the histological conclusion, MYCN gene status, immunohistochemical expression of MYC protein and the results of cytogenetic study of MYC gene status by FISH were known.

Results: MYCN gene amplification, 1p deletion/imbalance and 11q deletion/imbalance are more common in tumors from the unfavorable morphological group. Aberrations of the chromosomal region 1p and MYCN amplification are events that often occur together, while 11q aberrations, on the contrary, have an inverse correlation with MYCN amplification. 11q deletion/imbalance is more often detected in tumors with MYCN gain. In 4 cases, 1p and 11q chromosomal aberrations were detected in the same tumor, all in the unfavorable histological group. Two cases with chromosomal aberrations in stromal cells were also identified. Expression of MYC protein was detected in 5 cases, of which 2 showed amplification of the MYC gene.

The prevalence of chronic spontaneous urticaria (CSU) in the population is 0.5%-1%. According to modern guidelines for the management of patients with urticaria, the diagnosis of CSU does not require histological examination. However, in controversial clinical setting requiring differential diagnosis with urticarial vasculitis (UV), pathologists discover a wide range of pathomorphological changes in skin preparations in the absence of generally accepted differential diagnostic criteria. In this connection, it is of interest to study the spectrum of morphological changes in chronic spontaneous urticaria and urticarial vasculitis.

Objective: To analyze morphological changes in CSU and UV to improve differential diagnosis in clinical practice.

Material and methods: The material of 15 patients with urticarial rashes was analyzed. Comparative analysis of the number of neutrophils and mast cells in skin samples from patients with chronic spontaneous urticaria and urticarial vasculitis was performed.

Results: The material of 15 patients with urticarial rashes was analyzed. The group of patients with CSU (n=5) was characterized by the absence of signs of leukocytoclastic vasculitis; endothelial cells and mild of moderate swelling were visualized in all samples, the perivascular infiltrate was located in the upper layer of the dermis and was sparse. And when stained with toluidine blue, a large number of mast cells were noted. In the group of patients with UV (n=10), signs of leukocytoclastic vasculitis of varying severity, dense and deep perivascular neutrophilic infiltrates with a small number of mast cells were visualized.

Conclusion: Considering the wide range of morphological changes in the skin in CSU and UV, for the differential diagnosis of diseases, a comprehensive histological examination of preparations in combination with an assessment of the number of mast cells in the dermis and an assessment of the composition of the cellular infiltrate for the number of neutrophils can be recommended.

Gastric cancer (GC) is a heterogeneous tumor with various molecular changes. An active search for molecular markers is crucial to determine the effectiveness of drug treatment and prognosis of the disease. Several biomarkers have the greatest clinical significance: HER2, MSI / dMMR, PD-L1 (CPS), EBV and Claudin 18.

Objective: To study the frequency of HER2, MSI / dMMR and PD-L1 (CPS) in patients with operable GC depending on the tumor type according to P. Lauren.

Material and methods: The study included 600 patients with GC who underwent radical surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology from 2018 to 2023.

Results: In the study, the proportion of diffuse GC was 21.5% (120/600). HER2 overexpression was found in 5.2% (5/96) of cases with diffuse GC, 20.4% (37/181) of cases with intestinal GC, 10.1% (7/69) of cases with mixed GC (p=0.0029). The incidence of MSI was 3.3% (4/120) of cases with diffuse GC, 11.2% (28/251) of cases with intestinal GC, 7.3% (7/97) of cases with mixed GC (p=0.0378). PD-L1 expression (CPS> 1) was found in 42.3% (11/26) of cases with diffuse GC, 59.4% (35/59) of cases with intestinal GC, 27.3% (9/33) of cases with mixed GC (p=0.006). In poorly cohesive/signet ring cell cancer MSI occurred in 2.5% (2/79) of cases; HER2 overexpression - in 2.9% (2/68) of cases; PD-L1 (CPS> 1) - in 42.1% (8/19) of cases.

Conclusion: Our study demonstrated that in diffuse and poorly cohesive/signet ring cell GC the frequency of occurrence of the above clinically significant tumor biomarkers is lower compared to intestinal/mixed GC.

Endometriosis-associated fibrosis is a complex phenomenon, and the underlying mechanisms are still not fully understood. Fibrosis is invariably present in all forms of the disease and contributes to the classic endometriosis-associated symptoms such as chronic pelvic pain and infertility. The purpose of this literature review was to study the role of various cell populations, biological mechanisms and signaling pathways in inducing fibrogenesis of endometriosis lesions. PubMed and MEDLINE searched for studies published in English over the past 5 years that studied fibrosis in ovarian endometriosis.