Arkhiv patologii最新文献

{"title":"[Spectrum of morphological changes in chronic spontaneous urticaria and urticarial vasculitis].","authors":"V A Smolyannikova, O Yu Olisova, K S Teplyakova, A V Filatov, N A Larin","doi":"10.17116/patol20258702130","DOIUrl":"https://doi.org/10.17116/patol20258702130","url":null,"abstract":"<p><p>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.</p><p><strong>Objective: </strong>To analyze morphological changes in CSU and UV to improve differential diagnosis in clinical practice.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Results: </strong>The material of 15 patients with urticarial rashes was analyzed. The group of patients with CSU (<i>n</i>=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 (<i>n</i>=10), signs of leukocytoclastic vasculitis of varying severity, dense and deep perivascular neutrophilic infiltrates with a small number of mast cells were visualized.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 2","pages":"30-36"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Frequency of MSI, PD-L1 (CPS), HER2 in poorly cohesive gastric carcinomas].","authors":"S N Nered, R O Torosyan, N A Kozlov, H Sun, I G Avdyukhin, P V Kononets, I S Stilidi","doi":"10.17116/patol20258702111","DOIUrl":"https://doi.org/10.17116/patol20258702111","url":null,"abstract":"<p><p>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Results: </strong>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 (<i>p</i>=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 (<i>p</i>=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 (<i>p</i>=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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 2","pages":"11-17"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Pathogenesis of fibrosis development in ovarian endometriosis].","authors":"O I Patsap, O V Bratchikova, A V Babkina, M B Khabarova, S A Mikhalev, L M Mikhaleva","doi":"10.17116/patol20258702173","DOIUrl":"https://doi.org/10.17116/patol20258702173","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 2","pages":"73-78"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Microsatellite instability as a possible diagnostic marker of the gastric mucosa dysplasia].","authors":"A V Kononov, V A Rubtsov, M N Parygina, E V Demidova, S I Mozgovoi, E G Pomorgailo, A G Shimanskaya, M V Markelova","doi":"10.17116/patol2025870315","DOIUrl":"https://doi.org/10.17116/patol2025870315","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the MMR system proteins and the MSI status of regenerative (indefinite for dysplasia) and pronounced (epithelial dysplasia) gastric mucosa precancerous lesions in the comparison with cancer to determine their possible potential as a diagnostic markers of gastric mucosa dysplasia.</p><p><strong>Material and methods: </strong>The study included 2 groups of gastric mucosa specimens: (1) 150 biopsy gastric mucosa specimens: 43 with low-grade dysplasia, 32 with high-grade dysplasia, 75 - indefinite for dysplasia; (2) 155 cancer tissue specimens from resected stomachs. Gastric mucosa specimens were examined histologically, immunohistochemically using mouse monoclonal antibodies to the MMR system proteins: MLH-1, MSH2, MSH6, PMS2 (Diagnostic BioSystems, USA). MSI was studied with multiplex PCR evaluation of DNA microsatellites (NR-21, NR-24, NR-27, BAT-25, BAT-26) from paraffin sections, their analysis with capillary electrophoresis. The obtained data were processed with the Statistica 10.0 (StatSoft, USA), presented using descriptive, analytical statistics.</p><p><strong>Results: </strong>MSI was detected by immunohistochemistry in 8% (<i>n</i>=6) of the studied cases of low/high grade dysplasia, which does not have statistically significant differences from the distribution of MSI in the gastric cancer group (12% of microsatellite-unstable cases (<i>n</i>=18)) (<i>p</i>=0.49). MSI was not detected in any indefinite for dysplasia case.</p><p><strong>Conclusion: </strong>Detection of microsatellite instability in gastric mucosa dysplasia indicates the likelihood of its occurrence at the early stages of the carcinogenesis cascade and makes it possible to use it to assess the risk of gastric cancer associated with microsatellite instability. The absence of instability in cases indefinite for dysplasia determines the possibility of its use for differential diagnosis of truly neoplastic and regenerative/reactive changes in the gastric mucosa.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 3","pages":"5-16"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Pathomorphological characteristics of inflammatory and hereditary myopathies].","authors":"I S Limaev, N S Gladyshev, A M Emelin, Yu A Vetrova, S N Bardakov, R V Deev","doi":"10.17116/patol20258704131","DOIUrl":"10.17116/patol20258704131","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the immunophenotypic features of the inflammatory infiltrate cell composition and the morphometric features of muscle fibers in skeletal muscle biopsies from patients with hereditary and inflammatory myopathies, and to develop an integral coefficient to aid in the differential diagnosis of these conditions.</p><p><strong>Material and methods: </strong>The material is represented by biopsy specimens of m. tibialis anterior, m. vastus lateralis, m. gastrocnemius med, m. peroneus longus et brevis, m. deltoideus, m. biceps femoris and m. latissimus dorsi of patients with polymyositis (<i>n</i>=7), dermatomyositis (<i>n</i>=3), dysferlinopathy (<i>n</i>=10) and calpainopathy (<i>n</i>=3), established on the basis of molecular-genetic, clinical-instrumental and morphological data. All biopsies underwent pathohistological and immunohistochemical examination.</p><p><strong>Results: </strong>The number of necrotic muscle fibers was significantly higher in polymyositis compared to dermatomyositis (<i>p</i>=0.008), dysferlinopathy (<i>p</i>=0.003), and calpainopathy (<i>p</i>=0.009), showing a diffuse pattern. In dermatomyositis, necrotic muscle fibers were predominantly perifascicular. In dysferlinopathy, a positive correlation between CD68⁺-macrophages and CD4⁺-T-helpers in the perimysium (<i>p</i>=0.04) were observed. The number of CD8⁺-T-killer cells invading muscle fibers was higher in polymyositis compared to dysferlinopathy (<i>p</i>=0.034). Increased numbers of CD138⁺-plasma cells was also noted in polymyositis. The <i>MICE</i> coefficient was lower in hereditary myopathies.</p><p><strong>Conclusion: </strong>Immunophenotyping of the inflammatory infiltrate and quantitative morphometry using the integral <i>MICE</i> coefficient provide criteria for the differential diagnosis of myopathies of different origins. The established differences in the cellular composition of the infiltrate (particularly, the predominance of invasion by CD8⁺-T-killers in polymyositis) and in the degree of morphological homogeneity of muscle fibers (higher in hereditary forms) represent objective differential diagnostic criteria. Thus, the integrated application of these approaches can significantly improve the accuracy of verifying the differential diagnosis in myopathies of various origins.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 4","pages":"31-39"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Pathomorphological quality assessment of complete mesocolonectomy in right colon cancer].","authors":"I P Reznik, V A Avdeenko, A A Nevolskikh, R F Zibirov, V N Grinevich, S A Ivanov, A D Kaprin","doi":"10.17116/patol20258703162","DOIUrl":"https://doi.org/10.17116/patol20258703162","url":null,"abstract":"<p><p>Complete mesocolonectomy (CME) is the current standard of treatment for colon cancer patients. At the same time, there are currently no clear standards for the pathomorphological assessment of CME quality, allowing for a comprehensive and independent assessment of the quality of surgical treatment.</p><p><strong>Objective: </strong>Creation of a standardized system of pathomorphological assessment of the quality of TMCE based on the developed set of universal criteria.</p><p><strong>Material and methods: </strong>The prospective study included the results of treatment of patients with adenocarcinomas of the right half of the colon, who underwent surgical interventions in the volume of right-sided hemicolectomy (RSHE) in the period from 2022 to 2024. The method of pathomorphological examination included mandatory photo documentation, as well as mesocolonectomy quality assessment using the classification of N. West et al., visual assessment of CME quality using the classification of S. Benz et al., standard microscopic examination to determine the presence of metastatic lymph nodes (LN) lesions, dividing them into groups according to the Japanese classification.</p><p><strong>Results: </strong>The study included 142 patients, 116 (81.7%) of whom underwent laparoscopic interventions, while 105 (73.9%) had D3 lymphodissection. According to the pathomorphological study, the most common (65 cases - 45.8%) tumors were located in the ascending section of the transverse colon, multicentric tumor growth within the colon was detected in 3 (2.1%) cases. The overwhelming majority of patients had stage III (92 patients - 64.9%) and IV (25 patients - 17.6%) clinical stages of the disease.</p><p><p>The median of the studied LN was 48 (12-225), affected - 3 (1-51) LN. LN lesion was detected in 79 patients (55.6%). Damage to the apical LN was found in 9 (6.3%) cases. Unfavorable prognosis factors (perineural growth, lympho- and angiovascular invasion, the presence of tumor deposits and metastases in the lung) were identified in 92 (64.7%) patients.</p><p><p>Good quality of mesocolic fascia isolation (Grade 3) according to West was found in 101 cases (71.1%), true CME (Type 0 according to Benz) was performed in 74 cases (52.1%).</p><p><strong>Conclusion: </strong>The quality assessment of the removed specimen after RSHE should be based on a detailed examination of all removed lymph nodes with division into groups in accordance with the Japanese Clinical Classification, assessment of the plane of intestinal resection according to N. West and the quality of CME according to S. Benz.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 3","pages":"62-70"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Correlation of tumor budding with DNA mismatch repair system and PD-L1-status in gastric cancer].","authors":"T V Polushkina, D V Kalinin, N V Danilova","doi":"10.17116/patol2025870415","DOIUrl":"10.17116/patol2025870415","url":null,"abstract":"<p><strong>Objective: </strong>To detect the presence or absence of correlations between the degree of tumor budding (TB) and pMMR/dMMR (proficient Mismatch Repair System/deficient Mismatch Repair System) and PD-L1 status in gastric cancer (GC).</p><p><strong>Material and methods: </strong>Surgical material from 173 patients with verified gastric cancer of the tubular histological subtype, where the invasive edge of the carcinoma was examined, tumor budding were identified and counted by three methods: H. Ueno, L. Wang and, E. Karamitopolou. Patients with GC were divided into two groups - with low and high degree of tumor budding (LG-TB and HG-TB). dMMR and PD-L1 status were identified by immunohistochemical staining.</p><p><strong>Results: </strong>Using the H. Ueno method, a predominance of low-grade TB was found in the group of dMMR carcinomas (90.5% of dMMR cases were associated with LG-TB, <i>p</i>=0.035). According to the L. Wang method, 85.7% of dMMR cases were identified that were associated with LG-TB, <i>p</i>=0.028. According to the E. Karamitopolou method, it was found that 76.2% of dMMR cases were associated with LG-TB, <i>p</i>=0.106. When analyzing the relationship between tumor budding and PD-L1 expression, no statistically significant differences were found (<i>p</i>>0.05).</p><p><strong>Conclusion: </strong>The low degree of tumor budding, estimated by the methods of H. Ueno and L. Wang, correlates with the dMMR status of tumor tissue. No statistically significant association was found when counting tumor budding using the E. Karamitopolou method. The degree of tumor budding determined by any of the methods does not correlate with the PD-L1 status of GC.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 4","pages":"5-12"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Gastric tumors with GLI1 gene alterations (plexiform fibromyxoma and gastroblastoma). Case report and literature review].","authors":"I V Sidorov, A S Sharlai, D M Konovalov","doi":"10.17116/patol20258701137","DOIUrl":"10.17116/patol20258701137","url":null,"abstract":"<p><p>Plexiform fibromyxoma (PFM) and gastroblastoma (GB) are rare gastric tumors with a specific <i>MALAT1::GLI1</i> rearrangement, included in the conditional spectrum of neoplasms with alterations of the <i>GLI1</i> gene. The article presents a clinical case of PFM in a 6-year-old girl and a literature review highlighting current data on the morphology, immunophenotype and molecular genetic characteristics of PFM and GB. Despite the common genetic anomaly, differences in the morphology and clinical course of these tumors indicate the need for further research to clarify their relationship and potential reclassification in the light of new data on tumors with <i>GLI1</i> gene abnormalities. Integrating the accumulated knowledge about tumors with <i>GLI1</i> gene alterations into diagnostic algorithms and therapeutic approaches will help improve the treatment outcomes of patients with these rare neoplasms.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 1","pages":"37-40"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Immunohistochemical method of megakaryocytic lineage staining in bone marrow biopsy specimens as an additional pathomorphological differential diagnostic sign of primary myelofibrosis and essential thrombocythemia].","authors":"Z P Asaulenko, Yu A Krivolapov","doi":"10.17116/patol20258701122","DOIUrl":"10.17116/patol20258701122","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate and compare morphometric and histotopographic characteristics of megakaryocytic lineage in preparations stained with H&E or antibodies to CD42b in diagnostic trepanobioptates of bone marrow of patients with primary myelofibrosis and essential thrombocythemia with <i>JAK2</i> or <i>CALR</i> mutation. Analyze the dimensions and quantity of CD42b-positive megakaryocytes in 1 mm² area of section and assess suitability of these parameters as an additional differential pathomorphological criterion.</p><p><strong>Material and methods: </strong>108 trephine biopsies of the bone marrow from patients with primary myelofibrosis (N=53) and essential thrombocythemia (N=55) with <i>JAK2</i> or <i>CALR</i> mutation were selected. Digitized bone marrow slides stained with H&E or antibodies to CD42b (clone EP409) were the object of study. In every sample the average values of perimeter and area of megakaryocytes were analyzed, as well as the average number of megakaryocytes in 1 mm² area of myeloid tissue section. Logistic regression analysis was used to describe the relationship between CD42b-positive megakaryocyte characteristics and disease (primary myelofibrosis or essential thrombocythemia).</p><p><strong>Results: </strong>Immunohistochemical examination of bone marrow biopsy specimens using antibodies to CD42b in comparison with H&E staining allows to multiply the number of identifiable megakaryocytes in myeloid tissue by 3.5-4 times (<i>p</i><0.0001). Statistically significant differences in the mean values of the number of megakaryocytes in 1 mm² of the section area and megakaryocyte perimeter in patients with primary myelofibrosis and essential thrombocythemia have been demonstrated. ROC analysis (AUC=0.84, 95% CI 0.7782-0.9199) justifies the inclusion of the average perimeter size of CD42b-positive megakaryocytes and their number in 1 mm² of the section area in the differential diagnostic panel as an additional pathomorphological criterion.</p><p><strong>Conclusion: </strong>The revealed statistically significant differences in quantitative and geometric characteristics of megakaryocytes allowed to calculate differential threshold values of characteristics of megakaryocytic lineage of myeloid tissue in diagnostic trepanobioptates of bone marrow from patients with primary myelofibrosis and essential thrombocythemia. Counting the number of CD42b-positive megakaryocytes in one field of view at a magnification of 400 times was proposed as an additional pathomorphological differential-diagnostic sign.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 1","pages":"22-27"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Ultrastructural changes of skeletal muscle tissue of patients with dysferlinopathy].","authors":"I A Chekmareva, S N Bardakov, I S Limaev, A M Emelin, R V Deev","doi":"10.17116/patol20258701128","DOIUrl":"10.17116/patol20258701128","url":null,"abstract":"<p><p>Dysferlinopathy represents an orphan disease within the spectrum of progressive muscular dystrophies, occurring at a frequency of 1 to 9 cases per 1.000.000 individuals (Orphanet, 2024). It arises from mutations in the <i>DYSF</i> gene (OMIM 603009, 2p13, NM_003494.4), which is responsible for coding the transmembrane protein dysferlin. Dysferlin plays a critical role in the repair of muscle fiber membranes and the cellular processes of skeletal muscle regeneration. Although the molecular mechanisms of dysferlin-mediated repair are under active investigation, reports on the ultrastructural alterations in human skeletal muscles due to dysferlin deficiency are sparse.</p><p><strong>Objective: </strong>To identify the ultrastructural pathomorphological features of skeletal muscles in 6 patients with dysferlinopathy.</p><p><strong>Material and methods: </strong>This study presents pathomorphological, immunohistochemical, and ultrastructural data from skeletal muscle biopsies of 6 patients with molecularly confirmed dysferlinopathy.</p><p><strong>Results: </strong>Examination of paraffin-embedded sections of the anterior tibialis and vastus lateralis muscles, stained with hematoxylin and eosin, identified a primarily myopathic pattern of skeletal muscle injury. Immunohistochemical staining with dysferlin antibodies revealed the absence of the protein in muscle tissue compared to the positive control. Transmission electron microscopy has revealed ultrastructural alterations characteristic of dysferlinopathy, although not specific, including thickening and fragmentation of the basal membrane, thinning and lysis of myofibrils, folding and disruptions of the sarcolemma, destruction of mitochondria, and, newly described in this disease, necrosis of myosatellite cells and telocytes in skeletal muscles.</p><p><strong>Conclusion: </strong>Despite the non-specificity of the identified ultrastructural alterations, electron microscopy of skeletal muscle biopsies in dysferlinopathy can provide additional information about the mechanisms underlying the disease development. The finding of myosatellite cell and telocyte necrosis indicates the impairment of skeletal muscle regenerative capacity, which may be a novel link in the pathogenesis of dysferlinopathy.</p>","PeriodicalId":8548,"journal":{"name":"Arkhiv patologii","volume":"87 1","pages":"28-36"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}