Clinicopathological Correlation Research Articles

Interface change in early mycosis fungoides: A potential mimicker of benign dermatoses.

Histopathologic features of interface dermatitis can occasionally be seen in mycosis fungoides (MF), particularly in early patch-stage disease. We identified six patients with MF whose early biopsy specimens showed such prominent interface dermatitis that a benign diagnosis was favored. All subsequent specimens were reviewed for these patients, and the histopathologic evolution of disease was documented. Immunohistochemistry (IHC) for CD2, CD3, CD4, CD5, CD7, CD8, CD30, and CD123 was performed retrospectively. Educational archives were reviewed to assess the incidence of interface dermatitis in biopsies otherwise diagnostic of MF. A spectrum of vacuolar and lichenoid patterns of interface change was observed in this series of six patients eventually diagnosed as having MF, and was seen as a recurring pattern in multiple specimens over time. In retrospect, findings described in early MF such as lining up of lymphocytes along the dermal-epidermal junction within the basal layer, papillary dermal fibrosis, and intraepidermal lymphocyte atypia could be appreciated to varying degrees in the confounding specimens. CD123 was negative in all cases, putatively excluding a connective tissue disease (CTD). None of the early biopsies showed loss of pan-T antigens CD2, CD5, and CD7. Forty-six of 164 cases (28%) of MF in an archival study set showed varying degrees of interface dermatitis in the setting of otherwise diagnostic changes of MF. Early MF can show prominent interface change and mimic inflammatory dermatoses. Histopathologic clues suggestive of MF should be carefully assessed, and IHC for CD123 may be helpful in distinguishing MF from CTD. Repeat biopsies over time may be necessary to arrive at a definitive diagnosis, in conjunction with ancillary studies and strong clinicopathologic correlation.

Dermatology Journal of Cosmetic and Laser Therapy

Background: Cuproptosis is a recently discovered method of copper-induced cell death that serves an essential part in the progression and spread of stomach adenocarcinoma (STAD). Multiple studies have found that lncRNAs, or long non-coding RNAs, are strongly correlated with the outcome for STAD patients. However, the nature of the connection between cuproptosis and lncRNAs in STAD is still not completely understood. Our study set out to create a predictive hallmark of STAD based on lncRNAs associated with cuproptosis, with the hope that this would allow for more accurate prediction of STAD outcomes. Methods: We retrieved the transcriptional profile of STAD as well as clinical information from The Cancer Genome Atlas (TCGA). The cuproptosis-related genes (CRGs) were gathered through the highest level of original research and complemented with information from the available literature. We constructed a risk model using co-expression network analysis, Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) analysis to identify lncRNAs associated with cuproptosis, and then validated its performance in a validation set. Survival study, progression-free survival analysis (PFS), receiver operating characteristic (ROC) curve analysis, Cox regression analysis, nomograms, clinicopathological characteristic correlation analysis, and principal components analysis were used to evaluate the signature's prognostic utility. Additionally, ssGSEA algorithms, KEGG, and GO were employed to assess biological functions. The tumor mutational burden (TMB) and tumor immune dysfunction and rejection (TIDE) scores were utilized in order to evaluate the effectiveness of the immunotherapy. Results: In order to construct predictive models, nine distinct lncRNAs (AC087521.1, AP003498.2, AC069234.5, LINC01094, AC019080.1, BX890604.1, AC005041.3, DPP4-DT, AL356489.2, AL139147.1) were identified. The Kaplan-Meier and ROC curves, which were applied to both the training and testing sets of the TCGA, provided evidence that the signature contained a sufficient amount of predictive potential. The signature was shown to contain risk indicators that were independent of the other clinical variables, as demonstrated by the findings of a Cox regression and a stratified survival analysis. The ssGSEA study provided additional evidence that predictive variables were highly connected with the immunological condition of STAD patients. Surprisingly, the combination of high risk and high TMB reduced survival time for patients. A worse prognosis for the immune checkpoint blockade response was also suggested by the fact that patients in the high-risk group had higher TIDE scores. Conclusion: The potential clinical uses of the identified risk profiles for the 10 cuproptosis-related lncRNAs include the assessment of the prognosis and molecular profile of STAD patients and the creation of more targeted therapy strategies.

219 ISOLATED CORONARY OSTIAL STENOSIS DUE TO RECURRENT AORTIC WALL THROMBOSIS

Abstract Background Coronary ostial lesions are a rare entity and isolated coronary ostial stenosis is even less frequent. Diffuse coronary artery atherosclerosis is the main cause for the non-isolated stenosis, based on old post-mortem series and histological analysis of tissue removed during atherectomies. Case presentation A 49-year-old woman suffering from mild non-familial hypercholesterolemia reported to her family physician repeated episodes of chest pain related to exercise. During a cardiological outpatient evaluation, 12 lead electrocardiogram (ECG) and echocardiography turned out normal. During a stress test she had recurrent chest pain coupled with ECG ischemic changes (diffuse ST segment elevation). She was immediately referred to the emergency department where the ECG was back to normal and the troponin dosage within normal range. Coronary angiography was performed: non-selective cannulation revealed some irregularities of the aortic wall profile at the level of the right coronary ostium, with inability to visualize the right coronary artery. The selective cannulation of the left main coronary artery (LMCA), left anterior descending (LAD) and left circumflex branches showed a critical ostial stenosis at the origin of the LMCA without any other relevant lumen restriction, in a left-dominant pattern of coronary circulation. A suspicion of LAD dissection was raised when a laminar flux was observed at its origin. At the end of the procedure, the patient suddenly collapsed. The recorded rhythm was initially bradycardia, evolving to episodes of ventricular tachycardia for which multiple shocks were applied. Despite the resuscitation efforts, the patient never recovered. Autopsy was performed at the local hospital. At gross analysis, a non-uniform pale-tan thickening at the level of the sino-tubular junction was evident with involvement of both the right and left coronary ostia. Histological examination allowed to ascribe the thickening to recurrent thrombosis, without any underlying inflammatory process at the level of the aortic wall and with only minimal atherosclerotic plaques. No coronary artery dissection nor significant stenosis was present in all the coronary tree. Regarding the ventricular myocardium, one focus of replacement-type fibrosis was identified at subendocardial level in the infero-septal wall coupled with a small spot of loose connective tissue rich in hemosiderin-laden macrophages in the same region, consistent with an area of subacute ischemic damage. Conclusion Several series reported a higher frequency of isolated coronary ostial stenosis in women versus men. In fact, female sex along with hypertriglyceridemia have been recognized as independent risk factors for ostial lesions. The case herein reported highlights the diagnostic relevance of the autopsy investigation together with clinicopathological correlation, particularly in cases where the definite diagnosis can't be achieved in vivo.

HISTOPATHOLOGICAL APPROACH TO THE DIAGNOSIS OF BENIGN PERIPHERAL NERVE SHEATH TUMORS AT UNCOMMON LOCATION

Peripheral nerve sheath tumors are relatively common lesions that exhibit a wide morphological and biological spectrum. In the presence of classical morphological and immunohistochemical features, the histological diagnosis is usually straightforward, but they may represent diagnostic challenges. Schwannoma is a slow growing encapsulated tumor of neuroectodermal derivation that originates from the Schwann cells of the neural sheath. Most commonly presents as cerebellopontine angle mass but extracranial sites are known and needs to be considered in the differential diagnosis. Intraparotid and penile schwannomas are extremely rare. Their diagnosis could be missed on cytology due to cystic changes. Isolated plexiform neurofibroma of the tongue is again a rare tumor. Plexiform pattern recognition is important for the pathologist as these varients might show malignant transformation. Overall Fine needle aspiration cytology though inconclusive at times, help a lot initially to delineate between benign Vs malignant lesions. Moreover its minimally invasive so can be performed easily at the uncommon locations. Histopathology remains the gold standard. Clinicopathological and imaging correlation is must for definite diagnosis and treatment.

Neurophysiological consequences of synapse loss in progressive supranuclear palsy.

Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. We advocate that biophysical models of neurophysiology offer both a bridge from preclinical to clinical models of pathology and quantitative assays for experimental medicine. Such biophysical models can also disclose hidden neuronal dynamics generating neurophysiological observations such as EEG and magnetoencephalography. Here, we augment a biophysically informed mesoscale model of human cortical function by inclusion of synaptic density estimates as captured by 11C-UCB-J PET, and provide insights into how regional synapse loss affects neurophysiology. We use the primary tauopathy of progressive supranuclear palsy (Richardson's syndrome) as an exemplar condition, with high clinicopathological correlations. Progressive supranuclear palsy causes a marked change in cortical neurophysiology in the presence of mild cortical atrophy and is associated with a decline in cognitive functions associated with the frontal lobe. Using parametric empirical Bayesian inversion of a conductance-based canonical microcircuit model of magnetoencephalography data, we show that the inclusion of regional synaptic density-as a subject-specific prior on laminar-specific neuronal populations-markedly increases model evidence. Specifically, model comparison suggests that a reduction in synaptic density in inferior frontal cortex affects superficial and granular layer glutamatergic excitation. This predicted individual differences in behaviour, demonstrating the link between synaptic loss, neurophysiology and cognitive deficits. The method we demonstrate is not restricted to progressive supranuclear palsy or the effects of synaptic loss: such pathology-enriched dynamic causal models can be used to assess the mechanisms of other neurological disorders, with diverse non-invasive measures of pathology, and is suitable to test the effects of experimental pharmacology.

Erosive Pustular Dermatosis: Delving into Etiopathogenesis and Management.

Erosive pustular dermatosis (EPD) is a chronic inflammatory skin disorder that usually affects mature individuals. It predominantly affects the scalp and can lead to scarring alopecia. Risk factors include actinic damage and androgenetic alopecia. A traumatic insult to the skin is considered a vital trigger of the condition. EPD is a diagnosis of exclusion; thus, several neoplastic, infectious, vesiculobullous, and inflammatory conditions should be ruled out. Biopsy and clinicopathologic correlation are required to differentiate between EPD and these entities. A dysregulated, chronic immune response is considered central to the etiopathogenesis of EPD. We performed an evidence-based systematic review of the management options. There were predominantly studies with level IV and V evidence and only two with level III. Despite the responsiveness of EPD to potent topical steroids, such as clobetasol propionate, recurrence occurs after treatment withdrawal. With the available data, tacrolimus 0.1%, curettage-assisted aminolevulinic acid-photodynamic therapy, and systemic retinoids can be considered second-line options for EPD with a role in maintenance regimens. However, controlled data and more powerful studies are needed to make solid recommendations.

Association of Endogenous Metabolic End products & Clinicopathological traits of Oral Squamous Cell Carcinoma

Introduction: Oral squamous cell carcinoma (OSCC) is a widespread cancer and is associated with social and economic consequences. Clinico-pathological correlation improves patient survival and disease management. Our research intends to examine the relationships between OSCC and metabolic processes reflected by final catabolism products.
 Methodology: In this cancer comparative retrospective analysis, metabolic byproducts in OSCC patients and healthy controls were compared. One way ANOVA analysis was done to record notable changes in OSCC patients by correlating along with disease's clinico-pathological traits. 
 Result: Serum Urea and creatinine level were determined in a total of 109 subjects, 55 diagnosed as OSCC and 54 healthy subjects who had been reported to our hospital for the past two years. OSCC and healthy patients revealed blood urea levels with significant correlation (p=0.000). Serum creatnine was insignificant between two groups (p<0.68). Blood urea and creatinine was insignificant with random blood sugar (p<0.205), negative correlation with habits (p<0.953) and significant with metastasis (p=0.000).
 Conclusion: OSCC in advanced stages have nearing higher serum urea levels, and is associated with nodal metastases. Deregulation of protein catabolism processes may be associated with invasive characteristics of OSCC, enabling aggressive behaviour in OSCC.

Clinico-pathological correlations and outcomes of de novo glomerular diseases in patients after haematopoietic stem cell transplantation.

Various glomerular pathologies have been reported in patients who have undergone haematopoietic stem cell transplantation (HSCT), but the data on clinico-pathological correlations and clinical outcome remain limited. We analysed the clinical and histopathological data of patients who had biopsy-proven de novo glomerular diseases after HSCT since 1999. A total of 2204 patients underwent HSCT during the period 1999-2021, and 31 patients (1.4%) developed de novo glomerular diseases after a mean duration of 2.8±2.7 years after HSCT. Fifteen of these patients (48.4%) had graft-versus-host-disease prior to or concomitant with renal abnormalities. Proteinuria and eGFR at the time of kidney biopsy were 4.1±5.3g/day and 50.8±25.4mL/min/1.73 m2, respectively. Kidney histopathologic diagnoses included thrombotic microangiopathy (TMA) (38.7%), membranous nephropathy (MN) (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). Immunosuppressive treatment was given to patients who presented with nephrotic-range proteinuria and/or acute kidney injury, while renin-angiotensin-aldosterone blockade was given to all patients with proteinuria ≥1g/day, with complete and partial response rates of 54.8% and 19.4%, respectively. One patient with TMA progressed to end-stage kidney disease after 24 weeks, and two patients, one with TMA and one with MN, (6.4%) progressed to chronic kidney disease (CKD) Stage ≥3. Kidney and patient survival rates were 96.6% and 83.5%, respectively, at 5 years. De novo glomerular diseases with diverse histopathologic manifestations affect 1.4% of patients after HSCT, and approximately 10% develop progressive CKD.

A comprehensive review on pathogenesis, associations, clinical findings, and treatment of livedoid vasculopathy.

Livedoid vasculopathy (LV) is a thrombo-occlusive vasculopathy that involves the dermal vessels. Clinically, it is characterized by the presence of painful purpuric ulcers on the lower extremities. Histopathologically, it shows intraluminal fibrin deposition and thrombosis, segmental hyalinization, and endothelial proliferation. It is important to notice that the term "atrophie blanche" is descriptive and it includes not only patients with LV but also patients with a combination of vasculitis and vasculopathy, that is, LV and medium-sized vasculitis such as cutaneous polyarteritis nodosa (PANc). Diagnosis is based on a proper clinicopathological correlation, excluding the main differential diagnosis and considering vasculitis as a mimicker or concomitant diagnosis. Coagulation disorders must also be studied although they are not found in all LV. Its frequency is reviewed as well. Treatment of LV is challenging, and different therapies have been attempted. Among them, pain management, wound care, control of cardiovascular risk factors, and both antiplatelets and anticoagulants, mostly rivaroxaban, are the main therapies used. These different therapies as well as their degree of evidence are reviewed.

Clinicopathological Correlations in Enucleated Globes of Late-Stage Coats Disease with a Review of the Literature

Clinicopathological Correlations in Enucleated Globes of Late-Stage Coats Disease with a Review of the Literature

Clinicopathological Correlations in Enucleated Globes of Late-Stage Coats Disease with a Review of the Literature

Clinicopathological Correlations in Enucleated Globes of Late-Stage Coats Disease with a Review of the Literature

Determining Etiologic Diagnoses in Patients with Rapidly Progressive Dementia

AbstractBackgroundOverlap in the presenting clinical features and test results in patients with rapidly progressive dementia (RPD) confounds the etiologic diagnoses of RPD, contributing to diagnostic delays, missed treatment opportunities, and poorer outcomes. There is a need to improve diagnostic accuracy in patients with RPD, with particular emphasis on identifying patients with potentially treatment‐responsive causes of RPD early in the symptomatic course.MethodPatients with RPD were prospectively enrolled and evaluated in inpatient settings and outpatient subspecialty (memory) clinics at Washington University (Saint Louis, MO; 2016–2019) and Mayo Clinic (Jacksonville, FL; 2020–2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of widely accessible diagnostic testing and referencing established diagnostic criteria. Diagnostic disagreements were resolved via blinded review by a third specialist. Clinicopathologic correlation was evaluated using neuropathological and genetic data when available.Result160 patients with RPD were assessed, with average age‐at‐symptom onset 60.0±15.9 years; 50% were female. Diagnostic inter‐rater reliability (91% agreement; Cohen’s κ = 0.88, p<0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic or genetic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%—i.e., frontotemporal dementia, Lewy body dementia, vascular cognitive impairment), Creutzfeldt‐Jakob disease (15%), and other causes (15%—e.g., neurosarcoid, metabolic disruptions, neoplastic disease). The average age of patients with potentially treatable causes (AE and selected “other” causes; 54.4±18.2) was younger than those with neurodegenerative dementing illnesses (67.3±9.5) or CJD (67.4±7.9; p<0.001). Patients with potentially treatable causes were more likely to present with altered level of consciousness and seizures (p<0.05). CSF pleocytosis (>5 WBC/hpf) was more common in AE patients (p<0.05).ConclusionEtiologic diagnoses can be reliably established in RPD patients using available clinical data. Treatment‐responsive causes of RPD are common warranting consideration, particularly in younger patients with altered consciousness, seizures, and CSF pleocytosis.

Histopathological prognosticators and their clinicopathological correlation in oral squamous cell carcinomas of the tongue.

Tongue carcinomas account for 25%-40% of intraoral squamous cell carcinomas (OSCCs). Although TNM staging systems is an international standard for cancer reporting, prognosis evaluation, and treatment planning, multiple histopathological risk assessment predictors such as tumor thickness (TT), tumor shape, tumor growth pattern, and invasive malignancy grading scoring systems have been studied and should form a basis for prediction and prognostication of such aggressive carcinomas. To evaluate and characterize the histomorphological prognostic indicators in OSCCs of tongue and compare it with OSCCs of other anatomic sites within the oral cavity. Furthermore, to elucidate the significance of histopathological indicators in predicting prognosis of tongue squamous cell carcinomas (SCCs). Forty SCC cases with 20 each of tongue and 20 from other intraoral sites were retrieved from department archives. Clinical data and staging were obtained for each case. Histomorphological parameters including pattern of invasion (POI), tumor budding (TB), depth of invasion (DOI), TT, lymphocytic host response, tumor-associated tissue eosinophilia (TATE), vascular invasion, perineural invasion (PNI), and muscular invasion were assessed. The results were statistically evaluated. TB, DOI, and sarcolemmal spread were significant histologic predictors in tongue SCC. Upon correlation of histomorphological parameters with clinical staging, TT, POI, and TATE were observed to be significantly correlated (P ≤ 0.05). The histomorphological risk assessment model may serve as important addition to the existing prognosticators and may be used as a prognostic index to help plan and individualize treatment protocol in cases with aggressive high-risk disease for whom the use of multimodality treatment seems beneficial.

Histopathological features of pemphigoid gestationis and polymorphic eruption of pregnancy: A blinded retrospective comparative study of 31 cases.

Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) are pregnancy-related dermatoses. Definitive diagnosis often relies upon histopathology and direct immunofluorescence (DIF). PG is associated with fetal and neonatal risks, while PEP confers minimal risk. We aimed to compare histopathologic features to determine key differentiators. A retrospective cohort study of PG and PEP cases, with accompanying DIF, conducted from 1995 to 2020. Skin biopsies were examined independently in a blinded fashion by two dermatopathologists for a list of histopathological features. Twenty-one cases of PG and 10 cases of PEP were identified. PG had significantly denser eosinophils than PEP (mean 155 vs. 48 cells/5 hpf; p < 0.018). PG was also noted to have eosinophilic spongiosis and eosinophils at the dermal-epidermal junction more frequently compared to PEP (80% PG vs. 10% PEP; p < 0.001). A mean cutoff value of 86 eosinophils and a mean optimal sensitivity and specificity of 81% and 83%, respectively, for eosinophils density's diagnostic power of PEP versus PG were achieved. Subepithelial separation was exclusively seen in PG (40% vs. 0%; p < 0.007). Eosinophilic spongiosis, eosinophilic epitheliotropism, and dense superficial dermal eosinophils were diagnostic of PG. Given overlapping clinicopathologic features, however, DIF results with clinicopathologic correlation, remain the gold standard.

Leprosy in posteradication era – A clinicopathological correlation: How far we have achieved?

Background: Leprosy or “Hansen Disease” is chronic inflammatory disease caused by Mycobacterium leprae. This disease is the oldest disease known to mankind. Leprosy is also known as “Kushtaroga.”. Leprosy was considered as an eradicated disease in 2005 but still a large number of leprosy cases are being reported in India. Aims and Objectives: The aim of the study was to demonstrate that leprosy even being eradicated continuous to be a major health concern with changing trends. Materials and Methods: This study is a a hospital-based crossectional study; it involves all new patients of leprosy attending dermatology O.P.D HIMS, Safedabad, Barabanki, U.P. from 2015 to 2016. The cases were classified as per Ridley – jopling classification. Skin biopsies were taken from all clinically suspected cases of leprosy and these biopsies were studied using H&amp;E stain. Results: In our study, 53 leprosy cases were registered from April 2015 to April 2016. According to demographic details of leprosy cases, maximum number of cases were in the age group 31–40 years 38.9% and in individuals &lt;20 years 10.5%. Majority of cases were males (11.3%). The family history of leprosy was present in 9.4% of patients. Hypopigmented lesion on skin was most common symptom (32.1%). TT was most common clinical diagnosis (26.4%). IL was common histopathological diagnosis (26.4%). Atrophy of epidermis was seen in 50.9% of patients. Paucibacillary was seen in 62.3% of patients. Most of the cases were from Safedabad. Conclusion: Leprosy although reported to be eradicated still continues to be one of the common communicable disease in Uttar Pradesh, India. This necessitates to strengthen screening of cases, early detection, and revival of our knowledge regarding the disease.

CD44v6 expression in gastroenteropancreatic neuroendocrine neoplasms: Clinicopathological correlation and prognosis.

Clinical course of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) patients are determined by complicated and multifaceted factors. Ki-67 has been used to predict the behavior of NEN with statistically significant high probability. Immunohistochemical prognostic markers other than Ki-67 have been reported, but due to insufficient validation, they have not been used routinely. CD44 and its isoform variants showed significant inverse correlation with lymph node status, distant metastasis, and mortality in pancreatic neuroendocrine neoplasm (Pan-NEN). The aim of this study is to determine the prognostic value of CD44v6 expression among GEP-NENs. Immunohistochemical staining (IHC) of CD44v6 was studied in 26 formalin-fixed-paraffin-embedded (FFPE) specimens from GEP-NENs patients in the Srinagarind Hospital, Khon Kaen University, Thailand, between 2013 and 2018. Demographic data were collected. IHC staining result was interpreted based on H-score and correlated with neuroendocrine IHC markers, proliferation index, lymph nodes status, metastasis, and patients' survival. All cases showed variable staining for CD44v6 without statistically significant correlation with age, gender, histological grading, lymph node metastasis, distant metastasis, Ki-67 proliferative index, or neuroendocrine marker expression. Survival analysis showed association of higher CD44v6 expression with better prognosis (p=0.033). Hazard ratio of CD44v6 low expression patients with age ≥49 was 12.736 (p=0.028, 1.318-123.073), presence of lymph node metastasis was 8.267 (p=0.036, 1.142-59.841), presence of distant metastasis 12.736 (p=0.028, 1.318-123.073). Higher expression of CD44v6 IHC is significantly associated with better overall survival, histological grading, and Ki-67 index of GEP-NENs patients. CD44v6 IHC can be used as an additional prognostic immunohistochemical marker related to the metastatic status.

Hemispheric asymmetry and atypical lobar progression of Alzheimer‐type tauopathy

AbstractBackgroundNeurofibrillary tau pathology spread in Alzheimer’s disease (AD) mostly shows a stereotypical pattern of topographical progression. Atypical patterns have also been described and associated with interhemispheric asymmetry. As histopathological studies that used bilateral sampling are limited, this study aimed to assess interhemispheric tau pathology differences and the presence of topographically atypical cortical spreading patterns.MethodImmunohistochemical staining for detection of tau pathology was performed in 23 regions of interest of 57 autopsy cases and compared between cortical regions and hemispheres.ResultFrequent mild (82% of cases) and occasional moderate (32%) interhemispheric density discrepancies were observed while marked discrepancies were uncommon (7%) and restricted to occipital regions. Left and right hemispheric tau pathology dominance was observed with similar frequencies, except in Braak stage VI that favored a left dominance. Interhemispheric Braak stage differences were observed in 16% of cases and was more frequent in advanced (IV‐VI) than early stages (I‐III). One atypical lobar topographical pattern, where occipital tau pathology density exceeded frontal lobe scores, was identified in 4 cases, favoring a left dominant asymmetry.ConclusionWe speculate that asymmetry and atypical topographical progression patterns may be associated with described atypical AD clinical presentations and progression characteristics, which should be tested by comprehensive clinicopathological correlations.

A Study of Cyclin D1, E-cadherin, EGFR, HER- 2, Ki67, and p53 Tumor Marker Expressions in Neoplastic and Non -neoplastic Gall Bladder Lesions and their Clinico-pathological Correlation

Background: Worldwide gall bladder cancer (GBC) is known to be the commonest malignant tumour of the biliary tract. It is the most aggressive carcinoma of the biliary tract with short median survival from the time of diagnosis. The aggressive biologic behaviour of the carcinoma and non-availability of sensitive screening tests for early detection may be responsible for the poor prognosis associated with GBC.&#x0D; Material and Methods: Patients diagnosed with neoplastic and non-neoplastic gallbladder lesions in the Department of Pathology, Subharti Medical College in India were included in the study. Gall bladder biopsies findings and the clinic-pathological data were compiled and different immune-markers diagnostic and therapeutic usefulness were studied .&#x0D; Results: 24 (24.0%) of the cases were in the age group of 51-60 Years. In 38 (38.0%) of the cases the site of lesion was Fundus. 55 (55.0%) of cases had associated stones. 36 (36.0%) of them had P53: strong over expression, 40 (40.0%) of the them had ki67: strong over expression, 25 (25.0%) had EGFR: strong over expression whereas negative expression for Her2/Neu was found in 61 (61.0%) of the cases. Cyclin D1: moderate over expression was found in 27 (27.0%) of them and moderate over expression of E-cadherin were found in 22 (23.2%) cases.&#x0D; Conclusions: Novel prognostic biomarkers could bring about the needed breakthrough in gall bladder cancer diagnosis and treatment. We conclude that the biomarkers studied by us may help in the identification of cases who may benefit tremendously from adjuvant and targeted therapies.&#x0D; Key words: Cyclin D1, E-cadherin, EGFR, HER- 2, Ki67, p53, tumour marker, neoplastic , non –neoplastic, Gall bladder lesions.

Comprehensive analysis of anoikis-related long non-coding RNA immune infiltration in patients with bladder cancer and immunotherapy.

Anoikis is a form of programmed cell death or programmed cell death(PCD) for short. Studies suggest that anoikis involves in the decisive steps of tumor progression and cancer cell metastasis and spread, but what part it plays in bladder cancer remains unclear. We sought to screen for anoikis-correlated long non-coding RNA (lncRNA) so that we can build a risk model to understand its ability to predict bladder cancer prognosis and the immune landscape. We screened seven anoikis-related lncRNAs (arlncRNAs) from The Cancer Genome Atlas (TCGA) and designed a risk model. It was validated through ROC curves and clinicopathological correlation analysis, and demonstrated to be an independent factor of prognosis prediction by uni- and multi-COX regression. In the meantime, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration, and half-maximal inhibitory concentration prediction (IC50) were implemented with the model. Moreover, we divided bladder cancer patients into three subtypes by consensus clustering analysis to further study the differences in prognosis, immune infiltration level, immune checkpoints, and drug susceptibility. We designed a risk model of seven arlncRNAs, and proved its accuracy using ROC curves. COX regression indicated that the model might be an independent prediction factor of bladder cancer prognosis. KEGG enrichment analysis showed it was enriched in tumors and immune-related pathways among the people at high risk. Immune correlation analysis and drug susceptibility results indicated that it had higher immune infiltration and might have a better immunotherapy efficacy for high-risk groups. Of the three subtypes classified by consensus clustering analysis, cluster 3 revealed a positive prognosis, and cluster 2 showed the highest level of immune infiltration and was sensitive to most chemistries. This is helpful for us to discover more precise immunotherapy for bladder cancer patients. In a nutshell, we found seven arlncRNAs and built a risk model that can identify different bladder cancer subtypes and predict the prognosis of bladder cancer patients. Immune-related and drug sensitivity researches demonstrate it can provide individual therapeutic schedule with greater precision for bladder cancer patients.

FCGR3A: A new biomarker with potential prognostic value for prostate cancer.

To screen target gene cluster by bioinformatics analysis and verify them by in vitro experiment and clinicopathological correlation analysis. We try to find a new biomarker with prognostic value for prostate cancer (PCa). 42 candidate marker genes were constructed by protein protein interaction (PPI) network and enriched by KEGG pathway to find out the gene cluster we are interested in. Prognostic model was established to preliminarily analyze the prognostic value of this gene cluster in PCa, and Cox risk regression was used for comparative analysis. Immunohistochemistry was used to detect the expression of each gene in clinical tissue microarray. Finally, we analyzed the correlation between each gene and their clinicopathological features of PCa combined with TCGA clinical data. Based on the analysis of PPI and KEGG, we found the target gene cluster (FCGR3A, HAVCR2, CCR7 and CD28). Prognostic model analysis showed that this gene cluster had the ability to predict biochemical recurrence, and the survival rate and ROC analysis showed favorable prediction effect. Univariate Cox regression analysis showed that the risk scores of Gleason score (GS), T stage, N stage and PSA were significantly different (P<0.05), and the risk ratio of high expression was 2.30 times that of low expression (P=0.004). However, it was not statistically significant in multivariate Cox regression analysis (P>0.05). The results of tissue microarray showed that FCGR3A and HAVCR2 were highly expressed in PCa (P<0.01), while the expression of CCR7 and CD28 had no significant difference (P>0.05). Kaplan-Meier analysis showed that there was significant difference in BCR free survival of FCGR3A and HAVCR2 (FCGR3A, P=0.010; HAVCR2, P=0.018), while the expression of CCR7 and CD28 had no significant difference on the survival and prognosis of PCa patients (P>0.05). TCGA clinical data analysis found that the expression of FCGR3A had a unique correlation with the clinicopathological features of PCa, which was closely related to the tumor stage. The expression of FCGR3A is related to BCR free survival of PCa patients. Therefore, FCGR3A is a new biomarker with potential prognostic value of PCa.