Histopathological Scoring System Research Articles

Pseudomonas aeruginosa Infection and Inflammation in Cystic Fibrosis: A Pilot Study With Lung Explants and a Novel Histopathology Scoring System.

Pseudomonas aeruginosa is the predominant bacterial pathogen colonizing the cystic fibrosis (CF) lung. Mixed populations of nonmucoid and mucoid variants of P. aeruginosa have been isolated from the CF airway. While the association between mucoid variants and pulmonary function decline is well-established, their impact on inflammation and tissue damage in advanced CF lung disease remains unclear. This pilot study utilized 1 non-CF and 3 CF lung explants to examine lobar distribution, inflammation, and histopathology related to nonmucoid and mucoid P. aeruginosa infection. To study tissue damage, we developed a novel lung histopathology scoring system, the first applied to human CF lung biopsies, which is comprised of five indicators: bronchiolar epithelial infiltrate, luminal inflammation, peribronchial/bronchiolar infiltrate, peribronchiolar fibrosis, and alveolar involvement. Mucoid P. aeruginosa variants were distributed throughout the CF lung but associated with greater concentrations of proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-8, and IFN-γ, and one anti-inflammatory cytokine, IL-10, compared to nonmucoid variants. CF lung explants exhibited higher histopathology scores compared to a non-CF lung control. In mixed-variant infection, nonmucoid constituents associated with increased bronchiolar epithelial infiltration, one indicator of histopathology. This pilot study suggests ongoing interplay between host and bacterial elements in late-stage CF pulmonary disease. Mucoid P. aeruginosa infection correlates with inflammation regardless of lung lobe, whereas nonmucoid P. aeruginosa is associated with increased inflammatory cell infiltration. The development of a novel lung histopathology scoring system lays the groundwork for future large-cohort investigations.

Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children

BackgroundEnvironmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses. ObjectivesWe set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia (“EED”) with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as “normal”) or celiac disease. MethodsFive gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner’s glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value. ResultsBiopsies from the duodenal bulb showed higher intramucosal Brunner’s gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner’s glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan. ConclusionsThis scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED.

P-322 Development of a CD138-based histopathological scoring system to diagnose chronic endometritis

Abstract Study question Does a standardized histopathological classification system lead to a robust interobserver agreement to diagnose chronic endometritis (CE) and can an accurate computation algorithm be developed? Summary answer The proposed scoring system has a particularly good to excellent interobserver agreement among pathologists. A machine-learning algorithm outperformed pathologists in the clinically most relevant 2-tier-system. What is known already Plasma cell (PC) presence in the stromal endometrium has been proposed as a marker for CE, yet no standardized classification system that considers the amount or distribution of PCs exists. Also, interobserver agreement has been insufficiently reported in the previous publications on the topic. Without a robust histopathological score, the potential clinical impact of CE on ART treatment outcomes cannot be investigated. This issue is strongly reflected in the heterogeneity of the current diagnostic and therapeutic approaches, specifically for patients experiencing repeated implantation failure (RIF) or recurrent pregnancy loss (RPL). Study design, size, duration A 5-tier classification system based on CD138-positive PCs (Roche B-A38/automated Ventana system) was established: class0 (no PCs), classIPC (isolated PCs), class1 (³1 cluster of 5-19 PCs/0.25mm2), class2 (³1 cluster of 20-49 PCs/0.25mm2), class3 (³1 cluster of 50 or more PCs/0.25mm2). A test set of 78 endometrial biopsies (collected over two years) was selected by a certified pathologist who sorted >1000 biopsies to ensure the full spectrum of PC counts/distribution was accounted for. Participants/materials, setting, methods The 3DHistech-platform digitized the slides (pixel size 0.2738x0.2738mm) and a scoring session was set up in the Pathomation software suite. Six pathologists scored independently after training. Overall agreement was expressed by Fleiss’ Kappa values. Pairwise interobserver agreement was calculated using Cohen’s Kappa statistics. A supervised machine-learning algorithm was developed in QuPath(V0.4.2) and considered a seventh observer in the interobserver agreement calculations. Main results and the role of chance The CD138-based semiquantitative scoring system showed particularly good to excellent interobserver agreement among all observers. Overall agreement values were 0.722 for the 5-tier system and 0.858 for the 2-tier system (0+IPC versus 1 + 2+3, which was considered the clinically most relevant classification, i.e. CE absent versus diagnosed). Pairwise interobserver agreement was 0.871-0.951. Intra-class correlations varied from 0.727 to 0.839 in the 5-tier system and 0.893 to 0.965 in the 2-tier system. All findings were statistically significant (p < 0.001). The supervised machine-learning algorithm was able to compete with human pathologist observers and outperformed them in the 2-tier system. The proposed classification system provides a framework for assessing the presence and severity of endometrial PC infiltration and can guide further research. Limitations, reasons for caution Inconsistent staining intensity, non-specific epithelial staining and background interference are common problems that might limit interlaboratory use of the algorithm. Furthermore, the algorithm has not yet been associated to patient/clinical parameters. Accurate analysis of an endometrial biopsy might still be insufficient to provide a formal diagnosis of CE. Wider implications of the findings To unravel the association between PCs in endometrial biopsies (as a proxy for the diagnosis of CE) and the reproductive outcomes following ART, a standardized methodology is of crucial importance for future studies. Higher accuracy, efficieny and automation are advantages when using computer-aided diagnostics for CE. Trial registration number BUN 143202042810

Histopathologic Features of Drug Reaction With Eosinophilia and Systemic Symptoms.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction occurring 2 to 8 weeks after medication initiation. Diagnosis is clinical; RegiSCAR scoring includes biopsy "suggestive of DRESS," undefined in the literature. This study correlates DRESS dermatopathology, culprit drugs, disease course, and outcome severity compared with maculopapular drug reactions (MDR). Between 2014 and 2023, a retrospective cohort study at a tertiary care institute reviewed 55 patients with DRESS, assessing demographics, culprit drug, illness course, and histopathology. Biopsies of 15 patients with DRESS and 15 MDR patients were graded by a predefined histopathological scoring system. Statistical analysis (significant P -value<0.05) included the Fisher exact probability, ANOVA, and correlation tests. Among 55 patients with DRESS (mean age 50.13, 28 female/27 male), 15 (mean age 50.4, 7 female/8 male) had diagnostic biopsies. Compared with MDR patients, patients with DRESS exhibited significantly more interface dermatitis ( P = 0.04), lichenoid dermatitis ( P = 0.0007), pigment incontinence ( P = 0.04), and periadnexal interface dermatitis ( P = 0.002). MDR biopsies displayed perivascular inflammation and higher eosinophils than DRESS, trending toward significance. Key histopathologic features are interface dermatitis, periadnexal interface dermatitis, lichenoid dermatitis, pigment incontinence, and neutrophils dominance over eosinophils indicate DRESS clinically.

Histopathological and Immunohistochemical Study of Acute Tubular Injury in Native Kidney Biopsy.

Acute tubular injury (ATI) is a common diagnosis on renal biopsy. There are no accepted parameters to assess the severity of injury or predict recovery. An objective histologic grading system would be of immense value in clinical practice. The macrophage response to injury involves the MI phenotype which is proinflammatory and M2 which is prorepair. The study of these macrophages could aid in studying the severity and the recovery. A total of 58 native kidney biopsies with features of ATI and a minimum follow-up of 12 weeks were graded into mild, moderate and severe, using scores for simplification, sloughing, and mitosis. These scores and the density of macrophages stained with CD68, CD163, and HLA-DR were correlated with serum creatinine at presentation and with recovery. The effect of chronicity index as measured by glomerulosclerosis, tubular atrophy, and interstitial fibrosis and of co-morbidities of age, hypertension, and diabetes on the recovery pattern was also studied. All three histologic scores and the grades of ATI showed positive correlation with the serum creatinine level. The densities of CD 68 + and CD163 + macrophages also showed a significant correlation with serum creatinine level. However, none of these these histological features nor the macrophage densities predicted clinical recovery. Age >60 years, hypertension, diabetes, and chronicity score on biopsy were indicators of partial and delayed recovery. The histopathological semiquantitative scoring system can be used routinely to grade ATI. However none of the studied parameters predicted recovery.

Degrees of Inflammation in the Treatment of Subglottic Stenosis in a Rabbit Model: Histopathological Assessment of a Novel Bioabsorbable Ultra-high Ductility Magnesium Alloy Stent

ObjectiveUtilizing a novel histopathological scoring system and subglottic stenosis (SGS) rabbit model, we aimed to compare degrees of inflammation and severity of narrowing in the subglottis between two minimally invasive therapeutic modalities: endoscopic balloon dilation (EBD) alone versus EBD with placement of a bioabsorbable ultra-high ductility magnesium (UHD-Mg) alloy stent. MethodsSGS was induced endoscopically via microsuspension laryngoscopy in 23 New Zealand white rabbits. The control group (n = 11) underwent EBD alone, the study arm (n = 12) underwent EBD with implantation of bioabsorbable UHD-Mg alloy stents. Rabbits were euthanized at 2-, 3-, and 6-weeks after SGS induction, coinciding with wound healing stages. Using Optical Coherence Tomography (OCT), cross-sectional areas of airways were compared to calculate the mean percentage of intraluminal area at sequential time points. A novel histopathological scoring system was used to analyze frozen sections of laryngotracheal complexes. The degree of inflammation was quantified by scoring changes in inflammatory cell infiltration, epithelial ulceration/metaplasia, subepithelial edema/fibrosis, and capillary number/dilation. Univariate analysis was utilized to analyze these markers. ResultsWe found rabbits implanted with the bioabsorbable UHD-Mg alloy stent had statistically significantly higher scores in categories of hyperplastic change (stents vs controls: 1.48 vs 0.46 p < 0.001), squamous metaplasia (22 vs 5 p < 0.001), and neutrophils/fibrin in lumen (31 vs 8, p < 0.001). Rabbits who received EBD alone had higher scores of subepithelial edema and fibrosis (2.70 vs 3.49, p < 0.0256). The stented rabbits demonstrated significantly increased mean percent stenosis by intraluminal mean area compared to controls at 2 weeks (88.56 vs 58.98, p = 0.032), however at all other time points there was no significant difference between intraluminal subglottic stenosis by mean percent stenosis area. DiscussionRabbits with SGS treated with UHD-Mg alloy stents demonstrated histopathologic findings suggestive of lower levels of tracheal fibrosis. This could indicate a reduced tendency towards the development of stenosis when compared to EBD alone. There was not a difference in luminal size between stent and non-stented rabbits at the six-week end point. Histologically, however, overall the use of bioabsorbable UHD-Mg alloy stenting elicited a greater tissue response at the level of the superficial mucosa rather than fibrosis of the lamina propria seen in the stented rabbits. This suggests more favorable healing and less of a tendency towards fibrosis and stenosis even though there may not be a benefit from a luminal size standpoint during this early healing period. Compared to known complications of currently available non-bioabsorbable metal or silicone-based stents, this proof-of-concept investigation highlights the potential use of a novel biodegradable UHD-Mg stent as a therapeutic modality for pediatric SGS.

PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.

Development and Validation of a Diagnostic Histopathological Scoring System for Capsular Contracture Based on 720 Breast Implant Capsules.

Capsular contracture is traditionally evaluated with the Baker classification, but this has notable limitations regarding reproducibility and objectivity. The aim of this study was to develop and validate procedure-specific histopathological scoring systems to assess capsular contracture severity. Biopsies of breast implant capsules were used to develop histopathological scoring systems for patients following breast augmentation and breast reconstruction. Ten histological parameters were evaluated by multivariable logistic regression to identify those most associated with capsular contracture. Significant parameters (P < .05) were selected for the scoring systems and assigned weighted scores (1-10). Validation was assessed from the area under the curve (AUC) and the mean absolute error (MAE). A total of 720 biopsies from 542 patients were included. Four parameters were selected for the augmentation scoring system, namely, collagen layer thickness, fiber organization, inflammatory infiltration, and calcification, providing a combined maximum score of 26. The AUC and MAE for the augmentation scoring system were 81% and 0.8%, which is considered strong. Three parameters were selected for the reconstruction scoring system, namely, fiber organization, collagen layer cellularity, and inflammatory infiltration, providing a combined maximum score of 19. The AUC and MAE of the reconstruction scoring system were 72% and 7.1%, which is considered good. The new histopathological scoring systems provide an objective, reproducible, and accurate assessment of capsular contracture severity. We propose these novel scoring systems as a valuable tool for confirming capsular contracture diagnosis in the clinical setting, for research, and for implant manufacturers and insurance providers in need of a confirmed capsular contracture diagnosis.

The Predictive Role of the Histopathological Scoring System in Adipose Tumors-Lipoma, Atypical Lipomatous Tumor, and Liposarcoma.

Lipomatous tumors are the most frequent soft tissue neoplasms. Sometimes their differential diagnosis is difficult to perform only by microscopic analysis. This study aims to create a histopathological scoring system and highlight the impact of intratumoral microvascular density. This study was conducted over 10 years. We analyzed the main pathogenic pathways (MDM2 and CDK4), as well as the tumor microvascularization (CD31 and CD34) by immunohistochemical tests. We also analyzed the status of the MDM2 gene by CISH. These data, together with the clinical and histopathological information, were statistically analyzed by appropriate tests. We identified 112 eligible cases, with most of the patients being in their sixth decade of life, with a slight predominance of the female sex. We found important associations like tumor location linked to nuclear pleomorphism severity and microvascularization density correlated with atypia severity. Also, we observed that a maximum diameter of a tumor of at least 69 mm is associated with the presence of tumor necrosis. The score designed in this study shows an increased sensitivity and specificity for the diagnosis of lipomas (100%, respectively, 97%), atypical lipomatous tumors (93.8%, respectively, 82.3%), and liposarcomas (100%, respectively, 90.5%). This present study enhances the present data by bringing to attention the histopathological score with a role in differential diagnosis, as well as in the prediction of immunohistochemical and genetic tests. Also, we highlighted the importance of microvascular density, especially in the diagnosis of liposarcomas.

Efficacy of omental graft to facilitate canine radial fracture repair

PICO Question In dogs with a displaced radial fracture, does the use of a free autologous greater omental graft, combined with other standard fracture repair methods, compared to not using a greater omental graft, reduce fracture healing time? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three papers were critically reviewed: one retrospective clinical study and two experimental case control studies. All three papers answered the PICO question. Each of the three papers had a very small sample size, with two having a sample size of 16 (n = 4 in the relevant experimental group, and n = 4 for the control). The third had an initial sample of 25 that was later reduced to 19, as six dogs were excluded from the study. Strength of evidence Weak. Outcomes reported Two papers were experimental case control studies, which looked at radial fracture healing of dogs that had undergone an osteotomy, followed by bone plate and screw fixation, as well as either with a free autologous greater omental graft (OG) or without. Healing was measured in both studies via radiographical analysis using a modified Lane and Sandhu scoring system, and histopathological analysis post euthanasia with Heiple’s histopathological scoring system. Both studies found higher radiographic and higher histopathological scores in the OG group, though there was a large overlap between group scores. There was no mention of randomisation or power analysis in either of these studies, and blinding was only mentioned regarding histopathological analysis. The other was a retrospective study, looking at the outcomes of radial and ulna fractures in small breed dogs, after being surgically treated with a plate and screw, and either with or without OG. They found that dogs with omental grafts healed faster than those without, and had no major complications (whereas the non-OG group did). Note that this study was not (and could not) be randomised due to its nature, and it made no mention of blinding. Conclusion All three studies concluded that the use of OG assisted healing in canine radial fractures. However, care must be taken when applying these results to practice, as the studies lack robustness. While two of the studies had a good study design, both had very small sample sizes and neither mentioned randomisation. Blinding was only mentioned in the histopathological analysis, not radiographical analysis, and while both studies reported significant differences between their respective OG and control groups, they failed to account for multiple comparisons in statistical analysis, which likely skewed the results. The third study also represents a weak level of evidence, due to its retrospective nature and other limitations. Its small sample size, and the fact that 4/8 control (non-OG) dogs received a different type of graft, contributed to this. Due to the small number of animals in each study and the poor-quality design, it is concluded that there is weak evidence to support the PICO question. Further randomised blinded clinical trials with larger samples sizes are recommended, to increase the strength of the evidence before the routine clinical use of greater omentum grafts for aiding fracture repair can be recommended, considering that this means an additional abdominal surgical procedure. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Role of histopathology in severity assessments of post-COVID-19 rhino-orbital cerebral mucormycosis - A case-control study

BackgroundThere was an upsurge in rhino-orbital-cerebral mucormycosis (ROCM) during the second wave of the COVID-19 pandemic in India. Histopathological examination of the biopsies witnessed greater tissue invasion in these cases. The present study aimed to evaluate the histopathological scoring system in the severity assessment and to compare the scores between ROCM that required orbital exenteration (cases) and those that were treated conservatively (controls). Material and methodsA retrospective study was conducted to analyze the histopathological features using a scoring system in patients diagnosed with mucormycosis on sino nasal biopsies. The scoring was based on the following parameters: the extent of necrosis (score 1 <50% and score 2 >50%), degree of angioinvasion (score 1 <3 vessels in 10 fields and score 2 > 3 vessels in 10 fields), degree of inflammation (mild, moderate or severe), and fungal load(score 1 to 4), based on which three grades (I to III) were given. The scores were compared between the case group and the control group. The data obtained were analyzed statistically. ResultsThe study included 40 controls and 10 cases. The median age of patients in the control group was 52 with 82.5%males (n = 43) and 17.5 % females (n = 7) while in the case group, the median age was 51 years, and all were males. The predominant inflammatory response was of mixed suppurative type (70 %, n = 28). The degree of necrosis was scored 2 in 57.5 % (n = 23) of controls and 70 %(n = 7) in the case group. All the samples in the case group showed scores of 2 for angioinvasion and scores of 3 and 4 for fungal load. There was a statistically significant difference in the degree of necrosis, angioinvasion, the severity of neutrophilic infiltrates, and fungal load between the cases and controls (p-value <0.05). ConclusionThe present study analyses the predictive role of histopathology in invasive mucormycosis. Higher fungal load, degree of angioinvasion, and the absence of granulomas are associated with advanced disease in sinonasal mucormycosis. The study findings recommend incorporating the histopathological scoring criteria in evaluating patients with sinonasal mucormycosis.

Effects of different obesogenic diets on joint integrity, inflammation and intermediate monocyte levels in a rat groove model of osteoarthritis.

Introduction: Obesogenic diets aggravate osteoarthritis (OA) by inducing low-grade systemic inflammation, and diet composition may affect OA severity. Here, we investigated the effect of diet on joint damage and inflammation in an OA rat model. Methods: Wistar-Han rats (n = 24) were fed a chow, a high-fat (HF) diet, or a high-fat/high-sucrose (HFS) for 24weeks. OA was induced unilaterally 12weeks after the diet onset by groove surgery, and compared to sham surgery or no surgical intervention (contralateral limb). Knee OA severity was determined by OARSI histopathology scoring system. At several timepoints monocyte populations were measured using flow cytometry, and joint macrophage response was determined via CD68 immunohistochemistry staining. Results: Groove surgery combined with HF or HFS diet resulted in higher OARSI scores, and both HF and HFS diet showed increased circulating intermediate monocytes compared to chow fed rats. Additionally, in the HFS group, minimal damage by sham surgery resulted in an increased OARSI score. HFS diet resulted in the largest metabolic dysregulation, synovial inflammation and increased CD68 staining in tibia epiphysis bone marrow. Conclusion: Obesogenic diets resulted in aggravated OA development, even with very minimal joint damage when combined with the sucrose/fat-rich diet. We hypothesize that diet-induced low-grade inflammation primes monocytes and macrophages in the blood, bone marrow, and synovium, resulting in joint damage when triggered by groove OA inducing surgery. When the metabolic dysregulation is larger, as observed here for the HFS diet, the surgical trigger required to induce joint damage may be smaller, or even redundant.

Introducing a novel histopathological scoring system to assess disease activity and chronicity in cutaneous lichen planus: A proposal.

Lichen planus (LP) is a chronic inflammatory disorder caused by an autoimmune attack by cytotoxic T-cells. The clinical course is variable, with episodes of remission and exacerbation. A clinicopathological scoring system for cutaneous LP is not available for effectively assessing disease severity and monitoring treatment response. This study was designed with the aim of proposing an objective and reproducible scoring system, comprising histopathological features of active and chronic disease, and to correlate these scores with clinical morphology groups. This is a retrospective study of 200 cases of cutaneous LP, which were categorized into five clinical groups (I-V) at the time of biopsy. The corresponding histopathological feature was assigned a score based on feature of active and chronic disease. Individual scores were summated to calculate a histopathological index (index [AI] and chronicity index [CI]). The comparison of indices between various clinical groups was performed by Mann-Whitney U test. The median AI was lowest (1) for post-inflammatory hyperpigmentation (clinical group I) and highest (7) for the bullous group (clinical group IV). The median CI (7) was highest for the scarring group (clinical group V). The difference between median AI of clinical group I (post-inflammatory hyperpigmentation) and rest of the groups (clinical groups II, III, IV, and V) was statistically significant (p value <0.05). We present this clinico-histopathological scoring system as a reliable and facile method of assessing the activity and severity of LP.

Pediatric Adrenocortical Neoplasms: A Study Comparing Three Histopathological Scoring Systems.

Adrenocortical neoplasms are rare in childhood. Their histopathological categorization into benign and malignant is often challenging, impacting further management. While the AFIP/Wieneke scoring system is widely used for the prognostic classification of these tumors, it has limitations. Few other tumor scoring systems have evolved over the past few years. These have been validated in adults but not yet in pediatric patients. We evaluated a cohort of pediatric adrenocortical neoplasms to assess the applicability of AFIP/Wieneke criteria and the recently introduced Helsinki score and reticulin algorithm in predicting clinical outcomes. A tumor was considered 'clinically aggressive' in the presence of any of the following: metastases, recurrence, progressive disease, or death due to disease. Cases without any such event were considered 'clinically good'. Event-free survival time was the duration from the date of clinical presentation to any post-operative adverse event. For overall survival analysis, the endpoint was either the last follow-up or death due to disease.Using ROC curve analysis, the obtained cut-off Helsinki score of 24 could stratify the cases into two prognostically relevant groups. Survival analysis showed significant differences in the event-free and overall survival of these two groups of patients, validating the proposed cut-off. None of the three histopathological scoring systems could predict an unfavorable outcome with 100% accuracy. All showed a sensitivity of ≥ 80%, with the reticulin algorithm achieving 100% sensitivity. The specificity and accuracy of the AFIP/Wieneke criteria were the lowest (62.5% and 73.08%, respectively). While the Helsinki score (at the cut-off score of 24) and the reticulin algorithm had similar accuracy rates (80.77%, and 80%, respectively), the specificity of the former was higher (81.25%) than the latter (68.75%). A separate analysis revealed that the Ki-67 index at a cut-off of 18% had a sensitivity of 80% and a specificity of 81.25% for predicting an unfavorable outcome.

Understanding the Pathogenesis of Red Mark Syndrome in Rainbow Trout (Oncorhynchus mykiss) through an Integrated Morphological and Molecular Approach.

Red mark syndrome (RMS) is a widespread skin disorder of rainbow trout in freshwater aquaculture, believed to be caused by a Midichloria-like organism (MLO). Here, we aimed to study the pathologic mechanisms at the origin of RMS by analyzing field samples from a recent outbreak through gene expression, MLO PCR, quantitative PCR, and a histopathological scoring system proposed for RMS lesions. Statistical analyses included a One-Way Analysis of Variance (ANOVA) with a Dunnett's multiple comparisons test to assess differences among gene expression groups and a nonparametric Spearman correlation between various categories of skin lesions and PCR results. In short, the results confirmed the presence of a high quantity of 16S gene copy numbers of Midichloria-like organisms in diseased skin tissues. However, the number of Midichloria-like organisms detected was not correlated to the degree of severity of skin disease. Midichloria-like organism DNA was found in the spleen and head kidney. The spleen showed pathologic changes mainly of hyperplastic type, reflecting its direct involvement during infection. The most severe skin lesions were characterized by a high level of inflammatory cytokines sustaining and modulating the severe inflammatory process. IL-1 β, IL-6, IL-10, MHC-II, and TCR were upregulated in severe skin lesions, while IL-10 was highly expressed in moderate to severe ones. In the moderate form, the response was driven to produce immunoglobulins, which appeared crucial in controlling the skin disease's severity. Altogether our results illustrated a complex immune interaction between the host and Midichloria-like organism.

Pathological Spectrum and β-APP Immunoreactivity as a Diagnostic Tool of Diffuse Axonal Injury following Traumatic Brain Injury: A Novel Classification.

Aim Different deposition patterns and grading systems used to define and identify DAI remain discordant and to date these are a challenge in clinical practice. Our main objective was to study the post-mortem axonal changes and develop a grading system to identify DAI on the basis of histopathological and immunoreactive β-amyloid precursor protein (β-APP) observations in severe TBI cases. Methods Prospective study with 35 decedents with sTBI (GCS score ≤ 8) was conducted and samples were collected from three different sites-corpus callosum, thalamus and brain stem. Serial sections from each site were stained with hematoxylin and eosin (H&E), and immunohistochemistry (IHC) of β-APP. Results We developed a grading system based on histopathological characteristics to assess the overall damage of axonal injury. We found maximum histopathological changes in cases with prolonged stay. Corpus callosum showed maximum changes in both gradings. Curiously, we also detected axonal swellings with H&E staining. Usually neglected, the thalamus also showed significant histopathological and immunoreactive changes for sTBI. Conclusion Our study based on histopathological and β-APP scoring system to define and identify DAI thus facilitates accurate diagnosis of DAI post mortem, which has forensic implications, and may further contribute toward survival and improvement of quality of life of sTBI patients.

Amputation for Complex Regional Pain Syndrome: Meta-Analysis and Validation of a Histopathology Scoring System.

Pathology can provide crucial insights into the etiology of disease. The goal of this review is to evaluate the rigor of histopathology reports of Complex Regional Pain Syndrome (CRPS). A systematic search of multiple databases identified papers that described amputation for CRPS with pathology findings. Control pathology articles were randomly chosen from the same journals. Landmark articles in Surgical Pathology were previously identified. Papers were categorized by the use of histology: Anatomic (microscopic description), Diagnostic (binary result), and Substrate (special studies only). A novel Histopathology Score assigned 1 point for each of 10 History elements and 15 Pathology elements. All articles were scored and analyzed by appropriate statistics. The search identified 22 CRPS, 50 Control and 50 Landmark articles. Multivariable analysis of the Pathology Score showed a significantly higher score for Anatomic vs Non-Anatomic papers (Incidence Rate Ratio (IRR) 1.54, P < .001) and Landmark vs CRPS articles (IRR 1.39, P value .003). CRPS papers reported some elements infrequently: diagnostic criteria (31.8%), routine stain (50%), any clinic-pathologic correlation (40.9%), and sample size >2 (27.3%). The Pathology Score is a useful quality assessment tool to evaluate studies. As expected, Anatomic papers scored significantly higher than Non-Anatomic papers. CRPS papers had small sample sizes (median 1) and infrequent reporting of diagnostic criteria, routine stain, any clinical pathologic correlation. These particular elements are crucial for analyzing and reviewing pathologic features. The analysis explains why it is quite difficult to write a meaningful systematic review of CRPS histology at this time.

Minor Salivary Gland Surgery and Histopathological Scoring System: A Systematic Review

Sjögren’s syndrome is a systemic autoimmune disease characterized by chronic inflammation of the exocrine glands with an associated functional deficit. The clinical picture is characterized by symptoms such as dry eyes (xerophthalmia) and dry mouth (xerostomia). The disease is defined as primary if no other autoimmune diseases are associated, otherwise, it is defined as secondary. A systematic review was made using the databases PubMed (MEDLINE), Scopus, and keywords “biopsy,” “classification,” “clinical pathology,” “salivary glands,” and “Sjogren’s syndrome.” The diagnosis of Sjögren’s syndrome is based on a combination of clinical, serologic, instrumental, and histological features. In addition to ocular tests, a biopsy of the minor salivary glands represents one of the most relevant examinations for the diagnosis. In fact, the evaluation of specific histopathological features represents one of the most important criteria proposed in the last international consensus of 2016, which developed the most recent classification criteria for Sjögren’s syndrome. Knowledge of classification criteria, minor salivary gland biopsy techniques, and histopathological features are essential for the clinician to evaluate the pathology report and make a diagnosis of Sjögren’s syndrome. The aim of this review is to describe the classification criteria of the disease proposed to date, the main biopsy techniques used to analyze the minor salivary glands, and finally, the histopathological diagnostic scoring systems currently applied.

Histopathological scoring system role in evaluation of electronic cigarette’s impact on respiratory pathway in albino rat: Biochemical, histo-morphometric and ultrastructural study

BackgroundElectronic cigarettes have gained growing popularity especially among adolescents and young adults. Although the dominant consideration by consumers and the companies claims, whether electronic smoking is indeed a much safer alternative to traditional smoking is hotly debated. AimTo declare the biochemical, histopathological and ultrastructural impact of electronic cigarette exposure on the tissues of respiratory passage. Material and methodsTwenty adult male Wistar albino rats were allocated into two groups of 10 animals in each; group I as control group and group II which was exposed to 1 ml/day for one hour of E-liquid involving (18 mg/ml nicotine) for 5 sequential days/ week for 4 weeks. Assessment of markers of oxidative stress; malondialdehyde (MDA) & total antioxidant capacity (TAC) was performed. Specimens of their larynxes and lungs were subjected to histopathological examination with light microscopy (H&E, toluidine blue and orcein stain) with histopathological injury scoring, electron microscopic, histo-morphometric, and immune-histochemical studies of protein α-SMA, p53 and ki-67 ResultsE-liquid vapors exposed rats exhibited a significant elevation of MDA and suppression in TAC levels in comparison with the control group in all respiratory pathway organs. Microscopic analysis of respiratory epithelium of exposed group revealed hyperplasia, loss of their cilia and vascular dilatation in lamina propria while the lung examination showed thickened alveolar septa, inflammatory infiltrate and congested thick wall blood vessels. The bronchus was lined with multilayered dark stained nuclei epithelium, and there were thickened irregular smooth muscle fibers. Morphometric analysis revealed increase of area percent of elastic fibers in experimental rats’ lungs. Increase of α-SMA and P53 immuno-expression but decrease of Ki-67 immuno-expression in exposed groups were observed when compared to control. Ultrastructural examination showed cilial loss in respiratory epithelium with shrunken type 1 & 2 alveolar cells, with cytoplasmic vacuolations, atypical lamellar bodies and shrunken nuclei. Significant increase of the score of histopathological injury in larynx and lung. ConclusionExposure to e-liquid with nicotine induces oxidative stress and has adverse impact on respiratory pathway including histo-pathological and ultrastructural disorganization of respiratory epithelium and lung tissues.

Comparative Histopathology of Bovine Acute Interstitial Pneumonia and Bovine Respiratory Syncytial Virus-Associated Interstitial Pneumonia

Acute interstitial pneumonia (AIP) is a significant disease of cattle and many aetiologies have been implicated on the basis of the characteristic pathological lesions. Bovine respiratory syncytial virus (BRSV) is one of the key aetiological factors in bovine respiratory disease complex and several studies have suggested, controversially, that BRSV may be an underlying cause of bovine AIP. BRSV infection is known to cause several distinctive histopathological changes, including epithelial syncytia formation and intracytoplasmic viral inclusions. However, distinguishing bovine AIP from BRSV-related pneumonia by clinical presentation, gross pathology or histopathology can sometimes be challenging. In order to identify the potential distinguishing features, we compared the histopathological findings of AIP that were, and were not, associated with BRSV infection in naturally occurring cases. We found that multinucleated giant cells were more frequently identified in cattle with AIP while bronchiolitis was more common in BRSV-infected cattle. However, this was not considered a sole indicator of either disease group. Statistically, we identified that a combination of several histopathological features, including alveolar septal necrosis, presence of multinucleated giant cells and bronchiolitis, can serve as an excellent indicator for distinguishing between idiopathic AIP and BRSV-related pneumonia, with a strong statistical significance (P=0.0004). Based on the results of this retrospective study, we present a histopathological scoring system for predicting BRSV-associated AIP.