Arkhiv patologii最新文献

Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) is an essential enzyme capable of degrading asymmetric dimethylarginine, which is an endogenous inhibitor of nitric oxide synthase. Increased expression of DDAH1 and subsequent increased NO production are associated with carcinogenesis. In particular, DDAH1 is involved in the creation of a vascular network by tumor cells, vasculogenic mimicry, which is closely associated with tumor progression and poor patient prognosis. This is the reason why DDAH1 may be a potential therapeutic target for the treatment of cancer.

Sex cord tumor with annular tubules is a rare type of ovarian tumor, which seems to arise from Sertoli cells. Most tumors are associated with Peutz-Jeghers syndrome and have a benign course and favorable prognosis; however, about 20% of sporadic sex cord tumors with annular tubules have a high risk of developing metastases. We present a case report about 18-year-old patient who presented with irregular menstruation and abdominal pain. Based on the histological features and immunohistochemical results, the diagnosis of a sex cord tumor with annular tubules was confirmed. The above-described ovarian tumor is rare in childhood and adolescence compared to the general population, which, combined with nonspecific clinical manifestations, can result certain diagnostic difficulties in this age group of patients.

Sinonasal papillomas are a group of benign, relatively rare tumors of the sinonasal tract with varying clinical courses. In the modern WHO classification, it is customary to distinguish three subtypes of sinonasal papillomas: the most common inverted type (ISP), oncocytic type (OSP) and exophytic type (ESP). Recently, the concept has emerged that the different types of sinonasal papillomas may not be variants of a single tumor, but rather separate tumors. Thus, OSP demonstrates KRAS mutations, and the pathogenesis of ISP is associated with EGFR mutations.

Objective: To provide a comparative description of the EGFR gene (exon 20) based on the results of Sanger sequencing in sinonasal papillomas of inverted and oncocytic types.

Material and methods: Sanger sequencing of the EGFR gene (exon 20) was performed in 83 cases of sinonasal papillomas, of which 17 were of OSP and 66 were ISP cases. In 20 cases, an additional immunohistochemical study with an antibody to EGFR was also performed.

Results: When sequencing by Sanger of exon 20 of the EGFR gene in the ISP group, missense mutations were identified in 16 out of 66 cases, leading to a change in the value of the coding sequence of the gene, ultimately determining the formation of a different amino acid; this type of mutation was not identified in the OSP group. The most common mutation was at position 2622 in the form of G to A transition: in 47 cases of ISP (70%) and in 12 cases of OSP (71%). This mutation was synonymous and did not lead to an amino acid replacement in the synthesized protein. Thus, we did not find any significant differences in exon 20 of the EGFR gene between the ISP and OSP groups. In the ISP group, in 48 of 66 cases, multiple and single point mutations were noted, which we characterize as genetic heterogeneity.

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.

Objective: 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 JAK2 or CALR 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.

Material and methods: 108 trephine biopsies of the bone marrow from patients with primary myelofibrosis (N=53) and essential thrombocythemia (N=55) with JAK2 or CALR 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).

Results: 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 (p<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.

Conclusion: 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.

Plexiform fibromyxoma (PFM) and gastroblastoma (GB) are rare gastric tumors with a specific MALAT1::GLI1 rearrangement, included in the conditional spectrum of neoplasms with alterations of the GLI1 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 GLI1 gene abnormalities. Integrating the accumulated knowledge about tumors with GLI1 gene alterations into diagnostic algorithms and therapeutic approaches will help improve the treatment outcomes of patients with these rare neoplasms.

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 DYSF 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.

Objective: To identify the ultrastructural pathomorphological features of skeletal muscles in 6 patients with dysferlinopathy.

Material and methods: This study presents pathomorphological, immunohistochemical, and ultrastructural data from skeletal muscle biopsies of 6 patients with molecularly confirmed dysferlinopathy.

Results: 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.

Conclusion: 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.

The literature review presents an analysis of the pathogenesis and pathological anatomy of liver damage in COVID-19. Liver damage with the steatosis, vascular disorders, mild portal and lobular inflammatory infiltration, cholestasis and clinically - liver failure is observed in majority of the patients with COVID-19. Chronic liver diseases with infection SARS-CoV-2 tend to decompensate, which significantly worsens the prognosis of the disease. Pathogenesis of liver damage in COVID19 is unclear. There was no convincing evidence for the hypothesis of cytotoxicity for hepatocytes or cholangiocytes by SARS-CoV-2. Similar liver morphological changes described by different authors suggest their nonspecific nature and multifactorial pathogenesis related to hypoxia, cytokin storm, systemic inflammatory response syndrome, sepsis and shock, Covid-associated angio- and coagulopathy, as well as drug-induced hepatotoxicity. Further research is needed to clarify the pathogenesis and pathological anatomy of the liver pathology in COVID-19.

Polyposis rhinosinusitis (CRSwNP) is a heterogeneous proliferative disease characterized by inflammatory hyperplasia of the nasal mucosa with dysregulation of apoptosis and cell differentiation. The review summarizes data on the molecular cellular mechanisms of CRSwNP and presents the concept of intercellular signaling during polyposis growth. Various factors that form a specific endotype are involved in the development of a polyp. Features of morphogenesis make it possible to distinguish edematous, eosinophilic and fibrous NP. In all cases, markers of neurogenic inflammation, impaired expression of proinflammatory cytokines, NO synthase, BMP-2 and other morphogenetic molecules arerecorded. The growing polyp and the inflammatory reaction damage the epithelium of the mucous membrane and bone wall of the nasal cavity. Interleukin-1β and BMP-2 are an integrative link in the pathogenesis of these events.

There is no consolidated opinion on the pathogenesis of neurological manifestations of COVID-19, especially after infection. A significant contribution to understanding the mechanisms of neuropathology in COVID-19 can be made by detailed morphologic studies of the brain with assessment of changes in different brain regions during different periods of the infection process.

Objective: Clarification of the nature of brain morphologic changes and intracerebral virus invasion in COVID-19 and postinfection.

Material and methods: The study included 15 patients who died during the acute phase of COVID-19 (11 people) or after an infection (4 people) without a history of acute focal changes in the brain or neurological diseases. In each case, 9 brain areas were assessed, including the cortex, hippocampus, brainstem (pons and medulla oblongata), cerebellum, basal ganglia, and central parts of the olfactory system. In addition to the histological study, an immunohistochemical study was performed using antibodies against CD8, Iba1, as well as SARS-CoV-2 proteins (S1 and N) and a semi-quantitative assessment of circulatory disorders, microglial reaction and expression of the SARS-CoV-2 S1 protein in the brain.

Results: The neuropathological picture was similar in the acute and post-infectious phases of COVID-19: microcirculatory disorders, diffuse cerebral edema, ischemic-hypoxic neuronal changes, accumulations of corpora amylacea, gliosis, small mainly perivascular lymphocytic infiltrates with a predominance of CD8⁺ T cells, moderate microglial reaction, accumulation of SARS-CoV-2 S1 protein in the brain. The N protein of the virus was not detected in the brain. The most pronounced changes were observed in the brainstem, especially in the medulla oblongata, and the cerebellum. The severity of structural changes did not correlate with disease duration. S1 protein expression in the brain did not correlate with the severity of the microglial response or disease duration.

Conclusion: The identified neuropathological changes in COVID-19 in the acute and post-infectious phases are nonspecific with a predominance of vascular disorders and microglial reaction and are most pronounced in the brain stem and cerebellum. The SARS-CoV-2 S1 protein can accumulate in neurons and be detected in the brain a year or more after infection.