Histological Classes Research Articles

Flow Cytometry for the Detection and Quantification of Mast Cells in Lymph Nodes: A Prospective Study in 64 Dogs With Mast Cell Tumour.

Nodal metastasis is a negative prognostic factor in dogs with mast cell tumours (MCTs), thus early detection enables more informed decision-making and provides valuable prognostic information. The aim of this study is to assess the concordance between histopathologic findings of LNs and cytology and flow cytometry (FC), respectively, and to evaluate the ability of FC to differentiate between metastatic (HN2-HN3) and non-metastatic (HN0-HN1) LNs. Overall, 117 LNs from 64 dogs with first occurring MCTs were submitted for cytology, histology and FC. LNs were cytologically and histologically classified according to Krick and Weishaar systems, respectively. Using FC, mast cells (MCs) were identified as IgE+ CD117+ CD5- CD21- cells and quantified as a percentage. When compared with histologic classification, cytology showed an accuracy of 88.2% in distinguishing between metastatic and non-metastatic LNs but did not detect 25.3% of metastatic cases. FC revealed an increase in the median percentages of MCs across histologic classes, progressing from HN0 to HN3. ROC curves pinpointed 0.3% as the optimal cut-off for distinguishing between metastatic and non-metastatic LNs, with an accuracy of 84.3%. A 1.1% cut-off proved valuable in identifying HN3 LNs. The combined interpretation of cytology and FC increased accuracy to 92.2%. An algorithm for guiding the combined interpretation of cytology and FC is suggested based on these findings. In conclusion, FC proves beneficial in enhancing the early detection of metastatic LNs, particularly when utilised alongside cytology. Histopathology remains essential for confirmation, enabling the discrimination of HN classes or, in doubtful cases, for the detection or exclusion of nodal metastases.

Prognostic significance of tubulointerstitial macrophage density in MPO-ANCA-associated glomerulonephritis: implications for renal outcomes.

This study aimed to evaluate the density of tubulointerstitial macrophages with renal outcomes in patients with myeloperoxidase (MPO)-ANCA associated glomerulonephritis (MPO-ANCA GN). This study analyzed patients with MPO-ANCA GN who had renal biopsies at Jinling Hospital. It looked at the density of CD68+ macrophages in the tubulointerstitium and examined correlations with serum creatinine levels, urinary protein levels, treatment regimen, and renal histologic class. The study used KM curves to show the impact of these factors on renal prognosis and conducted multivariate analyses with Cox proportional hazards regression models. A total of 172 patients with MPO-ANCA GN (median age: 50 y, 43.6% male) were included. Stratification of the cohort into tertiles was based on tubulointerstitial macrophage density. Significant differences in serum creatinine levels, induction treatment regimen, the rates of ESKD, and renal histologic class were observed between the three groups. Correlation analysis showed that induction treatment regimen and renal histologic class were correlated with tubulointerstitial macrophage density. Kaplan-Meier curves illustrated patients with a lower presence of CD68+ macrophages in the tubulointerstitium experienced significantly better renal survival compared with those with a higher presence. The higher levels of CD68+ macrophage infiltration were significantly associated with adverse renal outcomes. This association persisted after adjusting for potential confounders including baseline serum creatinine, histopathological class, and induction therapy modalities. The results of our study provide insight into the prognostic significance of macrophage infiltration in the tubulointerstitium in MPO-ANCA GN.

Characterization of patients under 18 years of age with lupus nephritis at the Pablo Tobón Uribe Hospital and at the San Vicente Fundación Hospital in the city of Medellín between 2008 and 2017

IntroductionThe kidney is one of the organs frequently affected in systemic lupus erythematosus (40–60%); the manifestations are variable, from a silent pattern to the irreversible impairment of renal function. Materials and methodsDescriptive study with retrospective information in a group of patients under 18 years of age with a diagnosis of lupus nephritis, attended in two referral centres of the city of Medellin between 2008 and 2017. Clinical records of patients who met the inclusion criteria were reviewed. ResultsThe median age was 13 years, with predominance in females. The majority had renal involvement at the time of diagnosis of lupus. Histological class IV was the most frequent (48%). Age under 10 years, absence of response to induction therapy, and histological class IV, were related to the development of chronic kidney disease (>60 ml/min/1.73 m2). ConclusionsRenal involvement was higher in this study. Age, class IV, and non-response to induction were associated with impaired renal function.

Clinicopathological characteristics and renal outcomes of adult patients with pauci-immune necrotizing glomerulonephritis according to ANCA status.

Pauci-immune necrotizing glomerulonephritis (PING) is commonly associated with the presence of antineutrophilic cytoplasmic antibodies (ANCAs) but a significant number of patients do not have these antibodies. The significance of ANCA-negativity in the context of Berden's classification of PING is not known. A retrospective analysis was conducted on all patients with histopathological diagnosis of idiopathic PING irrespective of ANCA status diagnosed between January 1998 to December 2018 and followed up at renal clinic for > 12months. All biopsies were reclassified by Berden's classification. Clinicopathological characteristics and renal outcomes of ANCA-positive and ANCA-negative patients were compared. Out of 134 patients, 66 (49.5%) were ANCA-negative. The mean age was 34.76 ± 13.3years. Compared with the ANCA-positive patients, ANCA-negative patients had significantly greater prevalence of nephrotic-range proteinuria (74.23% Vs 57.9%, P = 0.036) with less extra-renal manifestations (P < 0.05)). On histology, focal and crescentic classes dominated with less number of globally sclerosed glomeruli (2.7% Vs 5.07%, P = 0.02) and more mesangial proliferation (22.7% Vs 4.41%, P = 0.002) in the ANCA-negative group, whereas sclerotic was predominant in the ANCA-positive group (P = 0.05). More patients achieved complete and partial recovery in ANCA-negative patients (42.4% Vs 20.5%, P < 0.05) with better renal survival (27.27% Vs 16.17%, log-rank test: P = 0.03) and less patient mortality (13.63% vs 30.8%, log-rank test: P = 0.04) at 2years. Our study confirms high prevalence of ANCA negativity among our cohort and this group presents with isolated renal involvement with better renal and patient survival. The ANCA-positive group showed significantly more patients in the sclerotic class, lower 2-year renal survival, and higher 2-year mortality as compared to the ANCA-negative group. However, the complete and partial responses to treatment were significantly better in the ANCA-negative group. Key Points • This study shows a high prevalence of ANCA negativity in cases of PING in Pakistani population, as almost half of patients in this study did not have these antibodies. • This negativity is more prevalent in the Asian populations but its significance in the context of Berden's classification of PING is unknown. • ANCA-negative group exhibited less severe phenotype and better outcomes compared with ANCA-positive group.

#2423 Molecular classification of lupus nephritis based on immune pathway profiling—correlations with histological class and clinical manifestations

Abstract Background and Aims The ISN/RPS 2003 classification is the current gold standard histopathological classification for lupus nephritis (LN), and has important roles in guiding treatment and predicting prognosis. The classification system, largely based on light microscopy features, does not inform the underlying immunological aberrations. A classification based on molecular typing of immune-related pathways may better stratify LN patients and help select treatments that target specific immune cascades. Method The normalized expression matrix and clinical data were extracted from Gene Expression Omnibus database, Human Cell Atlas (Hacohen-Human-CELseq2) and Nephroseq. Four chip datasets (GSE127797, 32591, 69438 and 37463) and one single cell dataset were analyzed. Sample gene set enrichment analysis (ssGSEA) method was used to derive immune phenotype with gene expression data. The hierarchical clustering with ssGSEA scores of selected gene sets was used to classify LN tissues. Functional characterization and protein-protein interactions of the differential expression genes (DEGs) of three groups were compared with healthy donors using Metascape (absolute log FC &amp;gt; 1 and adjusted P-value &amp;lt; .05). Kruskal-Walli test and chi-square test were performed to compare the clinical parameters of the different groups. Results We analyzed 96 immune-related gene sets in the glomerular and tubulointerstitial regions of LN kidney biopsy samples. The immune-related genes were categorized into three clusters (Immune-Mild, Immune-Moderate and Immune-Severe) based on the degree of immune pathway activation. Interferon-stimulated genes are a hallmark of LN, with high signals in all three clusters. When compared to other groups, the Immune-Mild cluster from the glomerular region showed no T-cell activation or T cell receptor pathway. Also, the Immune-Mild (tubulointerstitial) group also showed minimal lymphocyte activation or migration. Protein-protein interactions networks with MOCDE components further suggested that STAT1 and ISG15 the hub genes in different clusters. The gene expressions of hub genes were then compared among epithelial cells and 21 immune cells from LN and heath controls. Immune clusters are correlated with clinical phenotypes, in which Immune-Mild Group (Glomerular) showed high prevalence of Class II and V LN, and Immune-Mild (Tubulointerstitial) showed more Class V LN. Immune-Severe group also showed higher degree of proteinuria and blood pressure but lower eGFR compared to Immune-Moderate and Immune-Mild groups. Conclusion A new molecular classification of LN based on the degree of immune pathway activation shows correlation with clinical manifestations and may potentially guide personalized therapy in LN patients.

#2168 Lupus nephritis histopathological classification system: a questionnaire-based survey of the Renal Pathology Society (RPS)

Abstract Background and Aims Kidney biopsy is the gold standard for lupus nephritis diagnosis, defining histologic class, disease activity and chronicity in detail and providing guidance for treatment. The updated 2018 ISN/RPS histopathological classification in lupus nephritis is widely used for prognosis and treatment decisions. Given the evolving phenotypes of lupus nephritis and the success of new targeted agents in clinical trials, there is ongoing discussion about the need for updating existing classification systems. A survey to assess the current use of the lupus nephritis histopathological classification systems in everyday practice was conducted on behalf of the RPS. Method An online survey was sent between September 27th and October 24th, 2023 to active members of the RPS. The survey used an internet platform and contained both multiple-choice and open-ended questions; results were analyzed anonymously. Results 185 of 562 RPS members replied to the questionnaire. 179 (97%) were pathologists and the level of expertise in lupus nephritis was good: 120 (65%) participants indicated they encounter more than 20 biopsies with lupus nephritis per year, while only 13% encounter fewer than 10. Almost 90% of responders discuss kidney biopsy results in a multidisciplinary meeting involving both clinicians and pathologists, on a weekly or monthly basis. The 2018 ISN/RPS lupus nephritis classification is used in most cases (92%), while 7% of participants prefer the earlier 2004 version. The average grade on the utility of the 2018 ISN/RPS classification was 8 (IQR 7-9) on a scale from 0 (not useful) to 10 (extremely useful). Almost 90% of the pathologist responders indicated they include the NIH activity/chronicity indices in biopsy reports. Reasons for not adding the activity/chronicity indices were given as responses to open-ended questions: (1) clinicians usually do not ask for activity/chronicity indices—(2) the extra workload outweighs the perceived clinical benefit—(3) a quantitative description of the degree of activity/chronicity is less time-consuming and more understandable than the indices—(4) reproducibility is not guaranteed. The average grade on the utility of the activity/chronicity indices was 7 (IQR 7-9) on a scale from 0 (not useful) to 10 (extremely useful). Pathologists rated treating clinicians' understanding of kidney biopsy reports and lupus classification at light microscopy with an average score of 8 (IQR 7-9) on a scale from 0 (no understanding) to 10 (complete understanding). Suggested improvements of the 2018 ISN/RPS lupus nephritis classification were further standardization and simplicity. Clearer definitions were requested for: class III vs class IV; segmental sclerosis vs fibrotic crescents; the role of globally sclerosed glomeruli; lupus-like entities; and lupus podocytopathy. Furthermore, there was a request on guidelines for new parameters: e.g., focus on extraglomerular involvement, laboratory and clinical features and biomarkers; CD68+ staining to detect endocapillary hypercellularity; and EXT1/2 immunostaining. Conclusion Our survey shows the 2018 ISN/RPS lupus nephritis classification is widely used in everyday practice by pathologists, and well known by clinicians. The results obtained by the RPS survey serve as a starting point for the new Working Group of lupus nephritis classification. We will consider the ideas and suggestions of the international community to evaluate biopsies from extensively phenotyped cohorts, to modify the classification and to facilitate improved targeted treatment decisions—a current unmet need.

Update on Lupus Nephritis

Lupus Nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus (SLE), impacting up to 40% of SLE patients. Despite advancements in understanding the pathogenesis of LN, outcomes have not significantly improved since the early 2000s. LN patients face higher mortality, emphasizing the importance of achieving disease remission. Screening for nephritis involves regular monitoring, especially within the first 5 years of SLE diagnosis. Monitoring includes urinalysis, serum creatinine, and immune serology. Kidney biopsy remains the gold standard for LN diagnosis and classification, providing crucial information for treatment decisions. The standard of care involves hydroxychloroquine for all LN patients, with immunosuppressive treatments tailored to the histologic class. The recently approved medications, belimumab and voclosporin, offer additional therapeutic alternatives. Approximately 20% of LN patients exhibit features of thrombotic microangiopathy, warranting anticoagulation. Optimizing glucocorticoid dosing is recommended, favouring lower doses to minimize adverse effects. Lifelong monitoring is essential, as flares can occur at any point, emphasizing the need for continued immunosuppression. Given the lack of renal response in 30–60% of patients, the addition of combination therapies, such as calcineurin inhibitors or belimumab, should be considered. Duration of treatment is crucial, considering the progressive loss of podocytes and nephron function, which may lead to chronic kidney disease. Regular monitoring, maintenance immunosuppression, and lifestyle modifications contribute to preventing flares and improving long-term outcomes for LN patients.

Risk of chronic kidney disease in 260 patients with lupus nephritis-analysis of a nationwide multicentre cohort with up to 35 years of follow-up.

To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.

A Visualization Towards Oral Histology and Pathology Practical Classes - Existing Scenario and Imminent Trends

Introduction: Detailed knowledge is necessary in order to use dental anatomy, histology, and pathology in academic and clinical settings. Despite a competent, uniform academic curriculum and a passable infrastructure, there is still a disconnect between student comprehension and teacher preparation. Objective: To evaluate the difficulties dental students have learning the subject. Methodology: A cross-sectional survey was conducted among Students at College of Dental Surgery, In B.P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal. A semi-structured questionnaire was used to collect the socio-demographic data and to understand students’ interest in oral histology and oral pathology, to understand the difficulties encountered in slide identification and operating the microscope. Results: Out of 178 students, 161 participated in the study giving a response rate of 90.44%. Overall result shows a maximum positive response suggesting most of the students regularly attend classes and finish their assigned tasks. Here data suggests a mixed response, with some students having difficulty in slide identification and remembering the features although the students are quite comfortable with the use of microscopes. Conclusion: Understanding the slide and using the microscope effectively are a few of the difficulties that students encounter in oral biology and oral pathology. To improve student comprehension and proficiency in these areas, targeted interventions are necessary, as this study highlights these challenges.

Lung Cancer Proteogenomics: Shaping the Future of Clinical Investigation.

Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to lung cancer research, termed proteogenomics. The aim of this review article was to investigate proteogenomic approaches in lung cancer, focusing on how elucidation of proteogenomic features can evoke tangible clinical outcomes. A strict methodological approach was adopted for study selection and key article features included molecular attributes, tumor biomarkers, and major hallmarks involved in oncogenesis. As a consensus, in all studies it becomes evident that proteogenomics is anticipated to fill significant knowledge gaps and assist in the discovery of novel treatment options. Genomic profiling unravels patient driver mutations, and exploration of downstream effects uncovers great variability in transcript and protein correlation. Also, emphasis is placed on defining proteogenomic traits of tumors of major histological classes, generating a diverse portrait of predictive markers and druggable targets. An up-to-date synthesis of landmark lung cancer proteogenomic studies is herein provided, underpinning the importance of proteogenomics in the landscape of personalized medicine for combating lung cancer.

Risk of severe immune-related adverse events in cancer patients with pre-existing autoimmunity receiving immune checkpoint inhibitor therapy.

To evaluate the frequency and severity of irAEs in patients with pre-existing autoimmunity, including irAE-related morbidity and mortality, irAE-related management and resolution, and outcome of ICI rechallenge, to better understand the treatment options for this vulnerable patient population. We designed a retrospective, single-center, case-control study at a large, academic medical center to evaluate the incidence and severity of irAEs in patients with pre-existing autoimmunity compared to controls. Controls were matched 2:1 for age, sex, cancer histology, and ICI class. Patients were identified with ICD 9 and 10 codes followed by manual chart extraction. Cases were defined as patients with pre-existing, systemic autoimmunity. The primary outcome was severe irAE (Grade 3 or higher by Common Terminology Criteria for Adverse Events) within 6 months of ICI therapy. Secondary outcomes included response to ICIs, resolution of the irAE, ICI rechallenge success, and survival. Statistical analyses were performed by Chi-square, Fishers exact, Mann-Whitney, and Log-rank tests. Of 3,130 patients treated with ICIs from 2015-2021, 28 cases with pre-existing autoimmune disease were identified and were matched with 56 controls. Pre-existing autoimmune conditions included antiphospholipid syndrome, inflammatory polyarthritis, juvenile rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, rheumatoid arthritis, and type I diabetes. Multiple cancer histologies, including genitourinary, gynecologic, head & neck, hepatobiliary, lung, melanoma, and pancreatic, were represented. Six of 28 cases (21.4%) experienced severe irAEs compared to 9/56 (16.1%) controls; the odds of developing a severe irAE were not significantly different (OR 0.43, 95% CI 0.083-2.33, p = 0.627, ns). Moreover, there were no significant differences in overall survival or tumor response between the two groups. The majority of irAEs resolved without long-term sequelae (66.7% of cases, 55.6% of controls). The majority of patients who were rechallenged with ICIs were successful in continuing therapy (66.7% of cases, 100% of controls). Our study suggests that patients with pre-existing autoimmune disease can be treated with ICI cancer therapies and experience rates of severe irAEs and overall survival that are similar to those of the general population. These data can aid oncologists in discussing risks and benefits of ICIs when treating patients with pre-existing autoimmunity and solid tumors.

Deep representation learning of tissue metabolome and computed tomography annotates NSCLC classification and prognosis

The rich chemical information from tissue metabolomics provides a powerful means to elaborate tissue physiology or tumor characteristics at cellular and tumor microenvironment levels. However, the process of obtaining such information requires invasive biopsies, is costly, and can delay clinical patient management. Conversely, computed tomography (CT) is a clinical standard of care but does not intuitively harbor histological or prognostic information. Furthermore, the ability to embed metabolome information into CT to subsequently use the learned representation for classification or prognosis has yet to be described. This study develops a deep learning-based framework -- tissue-metabolomic-radiomic-CT (TMR-CT) by combining 48 paired CT images and tumor/normal tissue metabolite intensities to generate ten image embeddings to infer metabolite-derived representation from CT alone. In clinical NSCLC settings, we ascertain whether TMR-CT results in an enhanced feature generation model solving histology classification/prognosis tasks in an unseen international CT dataset of 742 patients. TMR-CT non-invasively determines histological classes - adenocarcinoma/squamous cell carcinoma with an F1-score = 0.78 and further asserts patients’ prognosis with a c-index = 0.72, surpassing the performance of radiomics models and deep learning on single modality CT feature extraction. Additionally, our work shows the potential to generate informative biology-inspired CT-led features to explore connections between hard-to-obtain tissue metabolic profiles and routine lesion-derived image data.

Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

Digital image analysis and machine learning-assisted prediction of neoadjuvant chemotherapy response in triple-negative breast cancer

BackgroundPathological complete response (pCR) is associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, only 30–40% of TNBC patients treated with neoadjuvant chemotherapy (NAC) show pCR, while the remaining 60–70% show residual disease (RD). The role of the tumor microenvironment in NAC response in patients with TNBC remains unclear. In this study, we developed a machine learning-based two-step pipeline to distinguish between various histological components in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of TNBC tissue biopsies and to identify histological features that can predict NAC response.MethodsH&E-stained WSIs of treatment-naïve biopsies from 85 patients (51 with pCR and 34 with RD) of the model development cohort and 79 patients (41 with pCR and 38 with RD) of the validation cohort were separated through a stratified eightfold cross-validation strategy for the first step and leave-one-out cross-validation strategy for the second step. A tile-level histology label prediction pipeline and four machine-learning classifiers were used to analyze 468,043 tiles of WSIs. The best-trained classifier used 55 texture features from each tile to produce a probability profile during testing. The predicted histology classes were used to generate a histology classification map of the spatial distributions of different tissue regions. A patient-level NAC response prediction pipeline was trained with features derived from paired histology classification maps. The top graph-based features capturing the relevant spatial information across the different histological classes were provided to the radial basis function kernel support vector machine (rbfSVM) classifier for NAC treatment response prediction.ResultsThe tile-level prediction pipeline achieved 86.72% accuracy for histology class classification, while the patient-level pipeline achieved 83.53% NAC response (pCR vs. RD) prediction accuracy of the model development cohort. The model was validated with an independent cohort with tile histology validation accuracy of 83.59% and NAC prediction accuracy of 81.01%. The histological class pairs with the strongest NAC response predictive ability were tumor and tumor tumor-infiltrating lymphocytes for pCR and microvessel density and polyploid giant cancer cells for RD.ConclusionOur machine learning pipeline can robustly identify clinically relevant histological classes that predict NAC response in TNBC patients and may help guide patient selection for NAC treatment.

Histopathological Findings of Epidermoid Carcinoma in the Nasal Cavity

It can be stated that neoplasms found in the cephalic and cervical regions are rare, given their incidence of only 3%, when compared to other malignant cancers that affect humans. Within this statistic, squamous cell carcinoma (SCC) stands out as the most common histological class. Such tumors, although uncommon, are of great clinical importance and their severity is closely related to the tumor stage at the time of diagnosis. Furthermore, it is worth highlighting that the location of the mass is of great importance, as it is a region made up of numerous noble structures, making surgical procedures unfeasible as a treatment option, given that there is extensive anatomical complexity. This research is characterized by being a case report of anatomical and histopathological findings of SCC (squamous cell carcinoma) in the right nasal cavity of a cadaver, with undetermined name, located at the Anatomical Center I of UNIFENAS, Alfenas campus.

Ultrastructural Examination of Glomerular Fibrillary Deposits in Diabetic Nephropathy

Glomerular fibrillary deposits have occasionally been reported in diabetic nephropathy, but no large-scale, ultrastructural evaluation of these deposits has been reported so far. Here, we report our study of glomerular non-Congophilic, DnaJ homolog subfamily B member 9 negative fibrillary deposits in diabetic nephropathy as characterized by transmission electron microscopy. Clinical data from 55 patients with biopsy-confirmed diabetic nephropathy and 18 healthy living donors were reviewed, and their biopsies were evaluated by light microscopy, immunofluorescence, and electron microscopy. Small fibrillary structures with a diameter of 10 ± 1 nm were present in all cases with diabetic nephropathy, regardless of the histologic class. In addition, glomerular fibrillary structures with a diameter of 23 ± 5 nm or 30 ± 7 nm were present in 35 cases. Interestingly, especially the small- and medium-sized fibrils, usually without apparent organization, were comparable with fibrils in fibrillary glomerulopathy. We conclude that glomerular fibrillary deposits occur far more commonly in renal biopsies of patients with diabetic nephropathy than generally considered. This is an important finding because their similarity to fibrils in fibrillary glomerulonephritis may complicate the histologic diagnostic process, especially in cases of overlapping clinical manifestations. Therefore, when encountering fibrillary deposits on electron microscopy, it is important to consider diabetic nephropathy as an alternative diagnosis.

Clinicopathological Correlation of Polyomavirus Nephropathy in Renal Allograft Recipients According to the Banff 2018 Classification.

Polyomavirus nephropathy (PVN) is a rare kidney disease caused by the BK virus, a strain of polyomavirus. The disease primarily affects transplant recipients, which is related to intensive immunosuppression protocol and can lead to kidney allograft failure. The objective of this study is to analyze histopathological features of PVN using the Banff 2018 PVN classification and to determine clinical features and outcomes of patients with PVN in each histologic class. The study included 44 patients who had been diagnosed with PVNby renal allograft biopsy in a large tertiary care hospital in Thailand from January 2011 to January 2020. The kidney biopsy slides were reviewed for Banff 2018 PVN classification and other histologic features. Patient demographic information, clinical data, and laboratory results were retrospectively collected. Nine (20.45%), 27 (61.36%), and eight (18.18%) cases of PVN were Class I, Class II, and Class III, respectively. The time from transplant to PVN diagnosis for Classes I, II, and III was four, 19, and 33.5months, respectively. Class III had the worst clinical outcomes in terms of deterioration of allograft function, the lowest rate of resolution, and the highest rate of graft failure. PVN classification provides prognostic information in renal allograft biopsy. Our study confirmed the validity of the three-tier histologic PVN classification put forward by the Banff Working Group in 2018.

Herpes zoster in lupus nephritis: experience on 292 patients followed up for 15 years.

To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN). This retrospective study included 292 LN patients to determine HZ incidence during the last decades and its correlation with LN activity. LN patients with HZ were matched with LN patients without HZ in a 1:2 ratio based on sex, age, year of LN diagnosis, and LN histological class at kidney biopsy to assess HZ risk factors. Statistical tests included t-test, U-test, and Fisher's test. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors. HZ occurred after LN diagnosis in 66 patients (prevalence 22.6%) with an average of 8.7 years (range 0.2-28.4 years). Although with the potential limitations of the retrospective nature and the extensive duration of the study, the incidence of HZ was 15.6/1,000 person-years, increasing from 6.9 before 1980 to 16.0 in the 1990s and 43.9 after 2010. HZ onset was unrelated to LN activity. LN was active in 43% of cases and quiescent in the other 57% of cases at HZ diagnosis. The percentage of patients who developed lupus flares during the year after HZ (18.9%) was not different from that which occurred during the year before HZ (17.2%, p = 0.804). After excluding confounding factors through matching, the univariate analysis suggested that cyclosporin during induction therapy (p = 0.011) and higher cumulative doses of glucocorticoids (GCs; >50g, p = 0.004), cyclophosphamide (CYC; >5g, p = 0.001), and mycophenolate mofetil (MMF > 1,000 g, p = 0.007) predisposed patients to HZ. Univariate and multivariate analyses revealed a protective role of azathioprine (p = 0.008) and methylprednisolone pulses (p = 0.010) during induction therapy. HZ occurs unpredictably throughout the course of LN, underscoring the importance of continuous monitoring for these patients. In addition, the incidence of HZ seems to have increased in recent decades. Induction therapy with azathioprine and methylprednisolone pulses appears to provide protection, while higher cumulative doses of GCs, CYC, and MMF increase susceptibility.

CSIG-13. DIELECTRIC PROPERTIES OF INTRACRANIAL TUMORS – ROLE OF MYELIN CONTENT

Abstract INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (GBM). One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity, which depends on the dielectric properties of the tumor tissue. In this study we determined the dieclectric properties of brain tumors by analyzing resected tissue. In GBM patients, histological analysis for cellularity, vascularization and myelin content was performed. In addition, sensitivity analyses for specific parameters were conducted. METHODS A cohort of 130 patients with tumors of different histology and malignancy grade have been recruited. Tissue samples were placed into a cylindrical cell with a known diameter. The impedance was recorded at frequencies 20Hz-1MHz. The measured impedance was translated into dielectric properties (conductivity and relative permittivity) based on the parallel plate model. Myelin, which is the most powerful electric isolator in the brain, was assessed in GBM samples by luxol fast blue staining, and quantified in a three-tier scale. To assess the impact of tissue conditions on the measurements, probes were warmed to 35 degree Celsius, dehydrated or irrigated with 0.9% saline solution. RESULTS We found significant differences between the conductivity of different types of tumors with meningiomas showing the lowest and GBM tissue exhibiting the highest conductivity values. GBM samples with very high median conductivity values displayed a consistently lower myelin content. In addition, GBM patients with particularly high conductivity had a significantly shorter overall survival (log rank analysis, p = 0.024). While tissue temperature had no detectable effects on the dielectric properties in GBM, saline irrigation tissue hydration significantly affected the results. CONCLUSION The dielectric properties of intracranial tumors depend on histological class and malignancy grade. GBM patients with high conductivity values showed a significantly poorer prognosis, indicating this parameter as potential marker for TTF efficacy.

Molecular Classification of Lupus Nephritis Based on Immune Pathway Profiling: Correlations with Histological Class and Clinical Manifestations

Molecular Classification of Lupus Nephritis Based on Immune Pathway Profiling: Correlations with Histological Class and Clinical Manifestations