Ultrastructural Pathology最新文献

Mesothelioma is often considered a difficult diagnosis due to its rarity, the wide variety of histological patterns and the propensity of metastasis from cancers of unknown origin to serosal surfaces. The advent of numerous new immunochemical markers has provided extensive aid in diagnosing epithelial mesotheliomas. However, immunochemical markers that assist in the diagnosis of sarcomatoid mesothelioma remain limited. Sarcomatoid mesothelioma is the most aggressive and least common form of mesothelioma. Therefore, sarcomatoid mesothelioma diagnosis has the added challenge of increased rarity in addition to a lack of distinctive immunochemical features. Electron microscopy (EM) is a useful tool for visualizing the ultrastructural components of different tumors and has been utilized to identify distinctive features in the diagnosis of epithelial mesotheliomas. Utilization of EM in cases of sarcomatoid mesotheliomas has been limited due to a lack of diagnostic ultrastructural markers. However, EM can still be useful in evaluation of sarcomatoid tumors when sarcomatoid mesotheliomas are part of the differential diagnosis. Here, we present the case of an individual with suspected sarcomatoid mesothelioma and demonstrate the utility of EM in differentiating alternative sarcomatoid malignancies, namely a myogenic sarcoma, by identifying diagnostic ultrastructural components.

Extensive research has begun to uncover the molecular characteristics of high grade gliomas. However, an ultrastructural understanding of their pathogenesis remains largely unexplored. Multinucleated giant cells are large cells with multiple nuclei thought to form from the fusion of multiple neoplastic cells. In this study, we aim to elucidate the nature of the multinucleated giant cells (MGCs) within IDH1-wild type glioblastoma (GBM) and IDH1-mutant astrocytoma, grade 4, by characterizing their phenotypes, ontogenies, morphologies, prevalence, significance, and potential impact on tumor progression and treatment resistance. Utilizing transmission electron microscopy (TEM), we examined 30 tumors (18 IDH1-wild type GBMs and 12 IDH1-mutant astrocytomas) and found that they share two types of MGCs. Type 1 is formed by the fusion of several tumor cells. Type 2 seems to be produced by tumor fibrillar cells filled with intermediate filaments (IF) and lipids through two processes, either by cell fusion or by the immigration of naked nuclei to a larger IF-filled tumor cell. Our results showed that MGCs are abundantly present in 43% of cases, making them less rare than previously believed. The two MGC types occurred solely or in combination in both types of gliomas. Furthermore, MGCs appear non-proliferative; and therefore, their contribution to tumorigenesis and proliferation is not yet fully resolved.

Light chain deposition disease (LCDD), an uncommon monoclonal renal disease linked to plasma cell neoplasm, can cause nephrotic syndrome and renal failure. Early diagnosis via renal biopsy is crucial. We describe a 51-year-old woman patient with multiple myeloma complicated with light chain nephropathy who presented with edema, proteinuria, and hypoalbuminemia. The serum-free kappa/lambda ratio was elevated. Renal biopsy revealed kappa light chain deposits, and electron microscopy revealed powdery electron-dense deposits, which confirmed the diagnosis. Chemotherapy and autologous stem cell transplantation reduced proteinuria and improved renal function. LCDD requires a prompt renal biopsy for diagnosis. Proteasome inhibitor-based therapies combined with stem cell transplantation significantly improve outcomes, highlighting the importance of early intervention in patients with renal impairment.

The development of new strategies to raise the survival and viability of transplanted mesenchymal stem cells (MSCs) is very important for the therapeutic potential of stem cells. The natural flavonoid myricetin has anticancer, antioxidant, anti-inflammatory and antiapoptotic effects. The effects of myricetin on human umbilical cord-derived MSCs (HUC-MSCs) induced oxidative stress with hydrogen peroxide (H₂O₂) were evaluated by transmission electron microscopy (TEM) and immunocytochemistry (ICC) staining. Myricetin showed an increase in the number of live cells, a decrease in caspase-3 and tumor necrosis factor-α (TNF-α) ICC staining intensity, an increase in the translocase of the mitochondrial inner membrane 17 (TIM17) ICC staining intensity, and a decrease in degeneration of cell ultrastructure in TEM against oxidative stress damage in HUC-MSCs. The results suggest that myricetin prevents oxidative stress-induced apoptosis and inflammation in the HUC-MSCs. Myricetin can be combined with HUC-MSCs in cell culture and considered as a supportive alternative treatment option.

Olanzapine (OLZ) is one of atypical antipsychotic drugs (second generation) used for treating schizophrenia, manic, and mixed episodes of bipolar disorder. Continuous evaluation of its effects is necessary, and there is a need to explore alternative natural products as G-CSF and UMB to manage potential side effects. This research designed to mitigate the atypical antipsychotic drugs' adverse effects through biochemical analyses, light and electron microscopic studies. Fifty-six rats were divided into five groups: Control, OLZ, G-CSF, UMB, and Recovery groups. End body and testicular weights, serum testosterone, testicular MDA levels, and seminal analysis were recorded. Testicular specimens were processed to evaluate histological structure, PCNA, and CD34 immune expression. Morphometric and statistical analyses were also performed. OLZ group exhibited a distorted testicular structure, a significant increase in end body and a decline in testicular weight, a significant decline in the serum level of testosterone level, testicular MDA, and seminal analysis parameters. Furthermore, disturbed histoarchitecture, reduction in PCNA, and elevation in CD34 immunoreaction were observed. These alterations were partially attenuated by G-CSF therapy, whereas UMB significantly improved all parameters. In conclusion, UMB, and to a lesser degree G-CSF, appeared to be superior therapeutic options by attenuating oxidative stress and restoring intact histological structure and biochemical parameters.

Chronic lymphocytic leukemia (CLL) is a prevalent hematological malignancy that significantly affects the kidneys as an extramedullary organ. Reports from autopsy studies have shown the infiltration of CLL cells into the renal parenchymal in 63-93% of cases. Glomerular diseases associated with CLL are relatively rare, occurring in approximately 2% of patients and often presenting as nephrotic syndrome. The most common histological pattern observed in CLL-associated glomerular diseases is membranoproliferative glomerulonephritis, followed by minimal change disease and membranous nephropathy. In this report, we presented a case of a 69-year-old male patient with CLL who developed nephrotic syndrome. The diagnosis of CLL was confirmed through bone marrow and renal biopsies, which revealed the presence of CLL tumor cells in the renal interstitium along with membranous nephropathy characterized by light chain-restricted deposits. The tumor cells present in the renal interstitium and glomeruli of the patient expressed identical light chain restrictions, which suggested that the membranous nephropathy was secondary and possibly induced by the deposition of tumor-associated antigens. Treatment with a combination of fludarabine, cyclophosphamide, and rituximab led to the remission of both the CLL and nephrotic syndrome, with no recurrence observed during the follow-up period.

We report here a challenging diagnosis of light chain crystalline podocytopathy in a patient with sub-nephrotic proteinuria, microscopic hematuria, glucosuria and elevated free kappa light chains but without any initial clinical evidence of frank multiple myeloma. We also discuss the diagnostic challenges of this case which include rather unique and seemingly innocuous light microscopic morphology of the glomeruli and the critical roles of paraffin immunofluorescence and need for electron microscopy to confirm the diagnosis. The kappa restriction of the crystals within the podocytes was confirmed only by paraffin immunofluorescence (it went undetected by routine immunofluorescence) and electron microscopy of the glomeruli showed the podocytopathy to be caused by electron-lucent crystals which is a rare variant of light chain crystals, with electron-dense crystals being the predominant variant of light chain crystals.

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder characterized by impaired ciliary structure and function, leading to chronic respiratory symptoms and recurrent infections. Despite its clinical significance, PCD diagnosis remains challenging due to its variable presentation and the lack of a gold standard diagnostic test. Specific clinical criteria, including neonatal respiratory distress and laterality defects, aid in suspicion of PCD, but confirmatory diagnosis often requires a combination of tests. In this study, we aimed to assess the efficacy of bronchoscopic techniques in obtaining respiratory epithelial samples for transmission electron microscopy (TEM) analysis. We enrolled adults with bronchiectasis and suspected PCD who underwent fiberoptic bronchoscopy. Bronchial forceps and brush biopsies were obtained from specific bronchial segments under conscious sedation. Tissue samples were processed for TEM analysis to identify ultrastructural axonemal defects associated with PCD. Our study included 10 patients (3 females, 7 males) aged 19-38 years, with detailed demographics and clinical characteristics provided. Evaluation of tracheobronchial biopsy samples revealed higher histological scores for the presence of ciliated cells and transverse sections of cilia in pellets obtained from brush biopsies and fixative solutions of forceps biopsy compared to forceps biopsy tissue samples. Electron microscopic examination of ultra-thin sections demonstrated abundant ciliated cells and abnormal cilia structures, aiding in the diagnosis of PCD in pellets. PCD represents a significant etiology of bronchiectasis, emphasizing the need for accurate diagnosis and appropriate management strategies. Our findings highlight the importance of bronchoscopic techniques, including bronchial brushing alongside forceps biopsies, in enhancing diagnostic yield and guiding timely intervention to improve patient outcomes.

The kidney is rich in mitochondria, and any alterations or damage to tubular cell mitochondria play an important role in renal metabolic activities and the pathogenesis of various kidney diseases. Quantitative analysis of mitochondrial concentration, size, and shape is essential for understanding mitochondrial biology in renal disorders. This study assessed mitochondrial morphometric parameters of the proximal convoluted tubular cell adjacent to the glomerulus in different renal disorders and investigated how they correlated with serum creatinine. A total of 65 kidney biopsy cases received by the transmission electron microscope (TEM) laboratory for diagnosis were included in the study. TEM images of glutaraldehyde-osmium tetroxide fixed epoxy-resin embedded 70 nm thick sections were used for the evaluation of (i) minor axis(MinX) (ii) major axis(MajX) (iii) Area, (iv)Perimeter, (v) Aspect ratio and (vi) Roundness of mitochondria in renal tubular cells using QuPath software. Mitochondrial density (MDensity), % of mitochondrial space (MSpace), and mitochondrial surface density (MSDensity) in the cytoplasm of tubular space were estimated for each sample. Serum creatinine showed good negative correlations with MSpace and MSDensity, and elongation of mitochondria was more in renal disorder in comparison to normal histology, which indicated the variation of mitochondrial concentration and shape in proximal tubular cells could be important features in the renal function disorder.

Atherosclerosis represents the most prevalent form of cardiovascular disease, with the potential to ultimately result in clinically significant complications such as myocardial infarction and stroke. The objective of our study was to gain a deeper understanding of the independent role of hyperlipidemia in the development of endothelial dysfunction and ultrastructural damage to the arteries, which is a key factor in the pathogenesis of atherosclerosis. Following a 12-week dietary intervention comprising either a high-energy diet (HED) or a normal diet (ND), fasting plasma glucose and lipid parameters were assessed. The aortas were subjected to histological analysis and Western blotting, while the carotid arteries underwent ultrastructural analysis using transmission electron microscopy. HED resulted in a statistically significant elevation in lipid parameters, even in normoglycemic P. obesus. eNOS, phospho-eNOS (Thr 495), and NF-κB p65 protein expression were increased in the aorta of HED-fed P. obesus. Histological examination and ultrastructural analysis of HED-fed P. obesus demonstrated notable vascular remodeling, manifested by segmental arterial wall thickening and the presence of large vacuoles and lipid droplets in endothelial cells. This study provides evidence that hyperlipidemia is a significant contributing factor to endothelial dysfunction and ultrastructural alterations in blood vessels, even in the absence of severe hyperglycemia.