Clinicopathological Manifestations Research Articles

Paraneoplastic pemphigus associated with squamous cell carcinoma of the cervix

Abstract Background Paraneoplastic pemphigus is an autoimmune skin and mucosal disorder, rarely associated with solid malignancies, with devastating impact. Patients and methods Herein, we report the case of a middle-aged patient who presented with recalcitrant stomatitis and was ultimately diagnosed with advanced-stage cervical cancer. Results Despite the prompt initiation of immunosuppressive medications, in parallel with systemic therapy for her underlying neoplasm, she eventually died within 10 months. Conclusions Considering its heterogeneous clinicopathological and immunological manifestations, paraneoplastic pemphigus remains a genuine diagnostic challenge, whereas its abysmal prognosis highlights the need of additional effective immunosuppressants.

Probiotics ameliorate IgA nephropathy by improving gut dysbiosis and blunting NLRP3 signaling

BackgroundRecently, a few studies have indicated a relationship between the gut microbiota and IgA nephropathy (IgAN). Whether the gut microbiota participates in the pathogenesis of IgAN and whether probiotics are effective in treating IgAN are still controversial. Therefore, this study aimed to identify the differences in the structure of the gut microbiota between IgAN and controls and to evaluate the efficacy and mechanism of probiotics in the treatment of IgAN.MethodsTo address this question, 35 IgAN patients and 25 healthy volunteers were enrolled, and a mouse IgAN model was also constructed. The stool microbes were analyzed by 16S rRNA high-throughput sequencing to identify the differential strains between IgAN and healthy controls. The impact of probiotics on the structure of the intestinal flora and the efficacy of the probiotics in the treatment of IgAN were evaluated.ResultsAlthough the microflora structure of mice and humans was not the same, both patients and mice with IgAN exhibited gut microbiota dysbiosis, with all subjects presenting an evident decrease in Bifidobacterium levels. The Bifidobacterium proportion was negatively correlated with proteinuria and hematuria levels, indicating that the decreased Bifidobacterium abundance could be related to IgAN severity. Probiotic treatment containing Bifidobacterium in IgAN mice could significantly alleviate gut dysbiosis, specifically by increasing the proportion of beneficial bacteria and reducing the abundance of potentially pathogenic bacteria. Moreover, both probiotics and their metabolites, short-chain fatty acids (SCFAs), could attenuate IgAN clinicopathological manifestations by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway.ConclusionsSupplementation with probiotics mainly containing Bifidobacterium could markedly improve gut dysbiosis in IgAN. Moreover, both probiotics and their SCFA metabolites could attenuate the clinicopathological manifestations of IgAN by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Therefore, probiotics have potential as an adjunctive therapy for IgAN.

LncRNA SAMD12-AS1 Suppresses Proliferation and Migration of Hepatocellular Carcinoma via p53 Signaling Pathway.

Purpose Assessment of lncRNA SAMD12-AS1 expression in liver cancer tissues and cell lines to investigate the underlying molecular mechanisms that regulate liver cancer cell growth, development, invasion, and migration. Methods The lncRNA SAMD12-AS1 expression in tumor tissues of 32 liver cancer patients was measured by real-time PCR, and its effect on the clinicopathological manifestations and liver cancer patients' prognosis was determined. LncRNA SAMD12-AS1 overexpression and knockdown in liver cancer cell lines were established by cell transfection. The effects of lncRNA SAMD12-AS1 knockdown and overexpression on liver cancer cell growth, development, invasion, and migration were determined by MTT, Transwell, and clonogenic assays. Furthermore, its effects on the expression of E-cadherin, vimentin, p53, and p21 in hepatocellular carcinoma cells were determined by Western blot assay. Results The level of lncRNA SAMD12-AS1 expression in tumor tissues was remarkably higher than that in paracancerous liver tissues (p < 0.01). It was found that the lncRNA SAMD12-AS1 expression was largely correlated with TNM stage of tumor, vascular invasion, and hepatitis B surface (HBs) antigen in liver cancer patients (p < 0.05). Cell function experiments showed that lncRNA SAMD12-AS1 overexpression promoted liver cancer development, migration, and invasion (p < 0.05), while lncRNA SAMD12-AS1 knockdown inhibited the activity of liver cancer cells to invade and migrate (p < 0.05). Western blot analysis showed that overexpression of lncRNA SAMD12-AS1 markedly inhibited p21, p53, and E-cadherin expression and promoted vimentin expression. Conversely, knockdown of lncRNA SAMD12-AS1 significantly promoted p21, p53, and E-cadherin expression and inhibited vimentin expression (p < 0.05). Conclusion LncRNA SAMD12-AS1 is associated with the TNM stage and vascular invasion of liver cancer. It promotes liver cancer cell development, invasion, and migration by regulating p53 expression. Thus, lncRNA SAMD12-AS1 could be a novel biological target for the treatment of liver cancer.

ANEURYSMAL BONE CYST OF THE JAWS: A SYSTEMATIC REVIEW

<h3>Objectives</h3> To integrate the literature data on aneurysmal bone cyst (ABC) of the jaws into a systematic review of the clinicopathologic features, treatment, and recurrence. <h3>Study design</h3> This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). PubMed, Web of Science, Scopus, and Embase electronic databases were searched. Case reports and case series reporting ABC of the jaws with predefined eligibility criteria were included. <h3>Results</h3> Out of 1,393 references, 151 articles (173 cases) met eligibility criteria. Female individuals (n = 88, 50.9%) with a mean age of 19.2 years (±12.35950 SD) were more affected. Regarding the anatomical location, the mandible (80.9%) was more affected. Clinically, most of the lesions presented as an extraoral swelling (n = 102, 50.2%), followed by intraoral swelling (n = 57, 28.1%). ABCs commonly presented as multilocular (n = 49, 20%) radiolucent (n = 93, 38%) lesions and 23.1% of the cases occurred in association with another lesion. Treatment of choice was mostly conservative (56.1%), presenting a low recurrence rate (n = 18, 10.4%). <h3>Conclusions</h3> Most of the ABCs included in this study occurred in young individuals presenting a low prevalence of recurrences. These results can help professionals to recognize the main clinicopathologic manifestations of ABCs.

HSV-1 Infection of Epithelial Dendritic Cells Is a Critical Strategy for Interfering with Antiviral Immunity.

Herpes simplex virus type 1 (HSV-1), an α subgroup member of the human herpesvirus family, infects cells via the binding of its various envelope glycoproteins to cellular membrane receptors, one of which is herpes virus entry mediator (HVEM), expressed on dendritic cells. Here, HVEM gene-deficient mice were used to investigate the immunologic effect elicited by the HSV-1 infection of dendritic cells. Dendritic cells expressing the surface marker CD11c showed an abnormal biological phenotype, including the altered transcription of various immune signaling molecules and inflammatory factors associated with innate immunity after viral replication. Furthermore, the viral infection of dendritic cells interfered with dendritic cell function in the lymph nodes, where these cells normally play roles in activating the T-cell response. Additionally, the mild clinicopathological manifestations observed during the acute phase of HSV-1 infection were associated with viral replication in dendritic cells.

Anti-neutrophil cytoplasmic antibody associated vasculitis in patients with rheumatoid arthritis

BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may coexist with rheumatoid arthritis (RA). However, it is unclear whether the manifestations of AAV with and without coexisting RA are similar. This observational study aimed to investigate the clinicopathological manifestations of AAV with coexisting RA and to explore potential predictors for identifying AAV superimposed on RA.MethodsPatients with both AAV and RA were identified by searching our hospital database and the literature. Data including age, sex, clinical manifestation, laboratory tests, renal pathology, and therapeutic regimens were retrieved. To assess the difference in clinical features and renal pathology between AAV patients with and without RA, we conducted 1:4 matched case-control studies.ResultsA total of 47 patients were identified, 15 from our hospital and 32 from the literature, and 33 (70.2%) were women. AAV was diagnosed later than RA in 83.0% of the patients and manifested as microscopic polyangiitis (MPA) in 78.7% of the patients. The kidney was the most frequently involved extra-articular organ (74.5%), followed by the lung (51.1%), and skin (8.5%). Patients with both AAV and RA were more likely to be asymptomatic (26.7% vs 3.3%, p = 0.013) than those with isolated AAV. However, they did not differ in other clinicopathological features. In RA patients, those with ANCA associated glomerulonephritis, were more likely to have decreased renal function at renal biopsy as opposed to those with primary glomerulonephritis.ConclusionsAAV can coexist with RA. In this coexistence, AAV usually develops after RA, is more likely to be asymptomatic, and manifests predominately as MPA with renal involvement. Thus, we should remain vigilant to superimposed AAV on RA.

Rigidoporus corticola Colonization and Invasive Fungal Disease in Immunocompromised Patients, United States.

We report 2 cases of Rigidoporus corticola (Oxyporus corticola) infection in humans in the United States. Clinical manifestations consisted of angioinvasive fungal sinusitis in 1 patient and pulmonary intracavitary fungus ball in the other patient. These cases illustrate previously undescribed clinicopathologic manifestations of infection by this filamentous basidiomycete in humans.

Macroscopic Distribution, Histopathology and Viral Antigen Expression in Dogs with Canine Distemper Virus-induced Hyperkeratosis in Nasodigital and Other Regions

Cutaneous hyperkeratosis is one of the many clinicopathological manifestations of canine distemper and is characterized by thickening and hardening of the skin, predominantly in nasodigital areas. Although this lesion may rarely affect other regions, this has been poorly characterized. Twelve dogs with canine distemper and cutaneous hyperkeratosis, necropsied at an anatomical pathology service, were investigated. Twenty-two cutaneous hyperkeratotic foci were observed on footpads (11/22), nasal planum (3/22), haired skin on the snout (2/22), periocular region (2/22), ventral abdomen (2/22), scrotum (1/22) and vulva (1/22). The dogs had one (5/12), two (4/12) or three (3/12) regions concomitantly affected. Orthokeratotic hyperkeratosis was a predominant histopathological feature in 17 dogs, occasionally accompanied by other lesions, including inclusion bodies (14/17), epidermal hyperplasia (9/17) and keratinocyte hydropic degeneration (6/17). Canine distemper virus antigen was expressed in at least one skin lesion in 10 dogs. Fourteen (14/17) hyperkeratotic foci were immunopositive while three (3/17) were immunonegative. Viral antigen expression was most common in the sweat glands (13/17), epidermis (11/17) and vascular endothelial cells or pericytes (8/17). Histological findings and antigen detection were similar among nasodigital and other regions. We emphasize the importance of clinicopathological recognition of these lesions for the initial suspicion of canine distemper, thereby facilitating early treatment.

Monoclonal Gammopathy-Related Kidney Diseases.

Monoclonal gammopathies occur secondary to a broad range of clonal B lymphocyte or plasma cell disorders, producing either whole or truncated monoclonal immunoglobulins. The kidneys are often affected by these monoclonal proteins, and, although not mutually exclusive, can involve the glomeruli, tubules, interstitium, and vasculature. The nephrotoxic potential of these monoclonal proteins is dependent on a variety of physicochemical characteristics that are responsible for the diverse clinicopathologic manifestations, including glomerular diseases with organized deposits, glomerular diseases with granular deposits, and other lesions, such as C3 glomerulopathy and thrombotic microangiopathy with unique pathophysiologic features. The diseases that involve primarily the tubulointerstitial and vascular compartments are light chain cast nephropathy, light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulin-induced nephropathy with distinct acute and chronic clinicopathologic features. The diagnosis of a monoclonal gammopathy-related kidney disease is established by identification of an underlying active or more commonly, low-grade hematologic malignancy, serologic evidence of a monoclonal gammopathy when detectable, and most importantly, monoclonal protein-induced pathologic lesions seen in a kidney biopsy, confirming the association with the monoclonal protein. Establishing a diagnosis may be challenging at times, particularly in the absence of an overt hematologic malignancy, with or without monoclonal gammopathy, such as proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Overall, the treatment is directed against the underlying hematologic disorder and the potential source of the monoclonal protein.

Clinicopathological Manifestations and Immune Phenotypes in Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibodies.

Anti-interferon (IFN)-γ autoantibodies (anti-IFN-γ Abs) is an emerging adult-onset immunodeficiency syndrome. Immune dysfunction in this distinct disorder remains to be clarified. We prospectively collected blood samples of 20 patients with anti-IFN-γ Abs and 40 healthy normal subjects. The percentages of lymphocyte subpopulations, most relevant to T, B, and NK cells, and the percentages of stimulated lymphocytes with cytokine production were assessed using eight-color flow cytometry. The results were adjusted to age and absolute lymphocyte counts. Most (85%) patients presented nontuberculous mycobacterial infection. Skin lesions were predominantly manifested by neutrophilic dermatoses. The involved lymph nodes had granulomatous inflammation, except 22.2% showing atypical lymphoid hyperplasia without granuloma formation. The percentages of CD4 + T cells and nonactivated subpopulations (recent thymic emigrants and naïve subtypes) decreased significantly with increased expression of activation markers and polarization to differentiated cells. The percentage of NK cells increased, but that of two major NK subpopulations, CD161 + CD56bright and CD161 + CD56 + CD16 + subsets, decreased. Increased CD161dim, CD161 + CD56 - CD16 + , and CD57 + NK cell subsets coupled with the decreased expression of NKp30 and NKp46 indicate reconfiguration of the NK cell population and acquisition of adaptive features. Intracellular cytokine production of the lymphocyte subpopulations was significantly low in the patients compared with the control group. We conclude that the immune system in patients with anti-IFN-γ Abs could be exhausted in T cells and be adaptive in NK cells, contributing to the distinct clinicopathologic features.

Qualitative Assessment of the Clinico-Pathological Features of Highly Pathogenic Avian Influenza H5N1 Outbreaks in Commercial Poultry and Peri-Domestic Birds in Northern Nigeria

The control of highly pathogenic avian influenza (HPAI) in Nigeria from inception is predicated on effective biosecurity by stamping out policy but outbreaks of the disease continued to re-occur with altered clinico-pathologic manifestations. This study undertook the qualitative assessment of the clinico-pathological features of HPAI H5N1 during the 2021/2022 outbreaks in commercial poultry and peri-domestic birds in northern Nigeria. A total of 22 commercial poultry farms with 53,932 laying chickens and 3 households with 120 backyard broiler chickens, 18 indigenous chickens, 10 peafowls and 9 geese were investigated for HPAI. The clinico-pathologic manifestations observed in commercial poultry were subtle compared to previous presentations of the disease except in the peafowls, geese, broilers and indigenous chickens. The interspecies mortality rates significantly varied from 1.6% to 19.6% for laying chickens and 33.3% to 100% for broilers, indigenous chickens, geese and peafowls. Based on the history of sudden and high mortality, clinical signs and post mortem lesions observed, three diseases; HPAI, very virulent Newcastle disease and fowl cholera were drawn out as differential diagnoses. However, a tentative diagnosis of HPAI was made and samples were sent to the National Veterinary Research Institute, Vom, Plateau State, Nigeria for confirmatory diagnosis. Results of the laboratory tests conducted on the samples using one step flu A screening and duplex real time RT-PCR, and virus isolation in embryonated chicken eggs confirmed HPAI H5N1 in twenty-five farms. It is concluded that the continuous though, irregular outbreaks of HPAI and emerging clinico-pathologic manifestations are pointers to failure of control and that the disease may become endemic. It is recommended that government should review its policy on the control of HPAI to include the adoption of zoned vaccination with close monitoring.

Diagnosis of soft tissue tumors using immunohistochemistry as a surrogate for recurrent fusion oncoproteins.

Soft tissue neoplasms encompass a broad spectrum of clinicopathologic manifestations. In a subset of soft tissue tumors, spanning a wide range of clinical behavior from indolent to highly aggressive, recurrent genetic translocations yield oncogenic fusion proteins that drive neoplastic growth. Beyond functioning as primary mechanisms of tumorigenesis, recurrent translocations represent key diagnostic features insofar as the presence of a particular oncogenic gene fusion generally points to specific tumor entities. In addition to more direct methods for identifying recurrent translocations, such as conventional cytogenetics or fluorescence in situ hybridization, immunohistochemistry for a component of the fusion oncoprotein increasingly is being used as a surrogate marker, exploiting the tendency of these fusion components to be distinctively overexpressed by translocation-bearing tumor cells. Diagnostic immunohistochemistry can also be used to identify the characteristic gene expression changes that occur downstream of oncogenic fusions. Here, we review the use of immunohistochemistry to detect surrogate markers of recurrent translocations in soft tissue tumors, focusing on the practical applications and limitations of this diagnostic approach.

Roles of Tenascin-XB in the Glioma Immune Microenvironment

Abstract Background: Previous studies have reported the critical roles of tumor cells and the tumor microenvironment in tumor prognosis and immunotherapeutic response. However, how Tenascin-XB (TNXB) expression relates to glioma prognosis and to the levels of tumor-infiltrating immune cells in various cancers has remained elusive. Therefore, this work aimed to investigate the expression, prognostic value, biological function and correlation between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues. Methods: First, we explored TNXB expression in glioma tissues by using online biological databases. Second, we assessed the clinical importance of TNXB expression with chi-squared tests, Cox regression and Kaplan-Meier curve analyses. Third, we examined the relationship between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues in an online database. Additionally, we assessed the associations of TNXB expression with genetic markers of immune cells and common immune-checkpoint molecules. Results: Elevated TNXB expression in glioma tissues correlated with tumor grade, according to several databases. Elevated TNXB expression was significantly associated with negative clinicopathological manifestations and poorer prognosis, on the basis of TCGA (n=510) data. Furthermore, univariate and multivariate Cox regression indicated that TNXB was an independent indicator of glioma prognosis. Pathway enrichment analyses suggested that TNXB participates in the immune response, humoral immune response and interferon-gamma-mediated signaling pathways. Importantly, TNXB expression was significantly associated with higher levels of tumor-infiltrating immune cells in diverse cancers. Furthermore, TNXB expression was strongly associated with genetic markers of immune cells and common immune-checkpoint molecules (e.g., PD-1, PD-L1, CTLA4, TIM-3, LAG3, PDCD1LG2, TIGIT and Siglec-15). Conclusions: TNXB expression correlates with poorer prognosis and higher levels of tumor-infiltrating immune cells in several cancers. In addition, TNXB expression is likely to contribute to the regulation of dendritic cells, exhausted T cells, regulatory T cells and tumor-associated macrophages in gliomas. Consequently, TNXB may serve as an important prognostic marker and may play an immunomodulatory role in tumors.

Inflammation-Related Long Non-Coding RNA Signature Predicts the Prognosis of Gastric Carcinoma.

Background: Gastric carcinoma (GC) is a molecularly and phenotypically highly heterogeneous disease, making the prognostic prediction challenging. On the other hand, Inflammation as part of the active cross-talk between the tumor and the host in the tumor or its microenvironment could affect prognosis. Method: We established a prognostic multi lncRNAs signature that could better predict the prognosis of GC patients based on inflammation-related differentially expressed lncRNAs in GC. Results: We identified 10 differently expressed lncRNAs related to inflammation associated with GC prognosis. Kaplan-Meier survival analysis demonstrated that high-risk inflammation-related lncRNAs signature was related to poor prognosis of GC. Moreover, the inflammation-related lncRNAs signature had an AUC of 0.788, proving their utility in predicting GC prognosis. Indeed, our risk signature is more precise in predicting the prognosis of GC patients than traditional clinicopathological manifestations. Immune and tumor-related pathways for individuals in the low and high-risk groups were further revealed by GSEA. Moreover, TCGA based analysis revealed significant differences in HLA, MHC class-I, cytolytic activity, parainflammation, co-stimulation of APC, type II INF response, and type I INF response between the two risk groups. Immune checkpoints revealed CD86, TNFSF18, CD200, and LAIR1 were differently expressed between lowand high-risk groups. Conclusion: A novel inflammation-related lncRNAs (AC015660.1, LINC01094, AL512506.1, AC124067.2, AC016737.1, AL136115.1, AP000695.1, AC104695.3, LINC00449, AC090772.1) signature may provide insight into the new therapies and prognosis prediction for GC patients.

Clinicopathological Characteristics Related to Etiologies of Erythema Nodosum: A 10-Year Retrospective Study.

BackgroundErythema nodosum (EN) is the most common panniculitis associated with a wide variety of conditions. Updated studies regarding the clinicopathological manifestations related to etiologies of EN and its prognosis are limited.ObjectiveWe aimed to explore the clinicopathological features in relation to the etiologies of EN and determine characteristics of disease recurrence and its predictive factors.MethodsA total of 169 patients with biopsy-proven EN or septal panniculitis from January 2008 to September 2018 were retrospectively reviewed. Patients were classified as either idiopathic or secondary EN. Patients’ general information, clinical manifestations, investigations, and recurrence of EN were recorded. The details on histopathological findings were reviewed by a blinded dermatopathologist.ResultsThe mean age at diagnosis of EN was 40.6 ± 17.3 years. The majority of patients (85.2%) were female. Idiopathic EN was found in 62.7% of patients. Tuberculosis (23.8%) and drugs (23.8%) were the leading causes of secondary EN. In univariate logistic regression analysis, lesions on upper extremities (p = 0.018), fever (p = 0.003), clinical lymphadenopathy (p < 0.001) favored secondary EN. Histopathologically, the presence of focal peripheral lobular panniculitis with eosinophils was linked to idiopathic EN (p = 0.03). However, multivariable logistic regression analysis failed to demonstrate factors associated with secondary EN. Recurrence was found in 46.6% of patients with no identifiable predictive factors.ConclusionAlthough no clinical risk factors were associated with the etiology of EN, the histopathological presence of eosinophils in focal peripheral lobular panniculitis suggested idiopathic EN.

Multicentric Castleman disease and the evolution of the concept.

SummaryThe term multicentric Castleman disease (MCD) encompasses a spectrum of conditions that share some overlapping clinicopathological manifestations. The fundamental pathogenetic mechanism involves dysregulated cytokine activity, causing systemic inflammatory symptoms as well as lymphadenopathy. Some of the histological changes in lymph nodes resemble the histology of unicentric Castleman disease (UCD). However, based on current knowledge, the use of this shared nomenclature is unfortunate, since these disorders differ in pathogenesis and prognosis. In Kaposi sarcoma-associated herpesvirus (KSHV)-associated MCD, cytokine overactivity is caused by viral products, which can also lead to atypical lymphoproliferations and potential progression to lymphoma. In idiopathic MCD, the hypercytokinemia can result from various mechanisms, which ultimately lead to different constellations of clinical presentations and varied pathology in lymphoid tissues. The authors review the evolving concepts and definitions of the various conditions under the eponym of multicentric Castleman disease.

Anti-HMGCR myopathy: clinical and histopathological features, and prognosis.

This review aims to describe clinical and pathological features, prognosis and treatment in patients with anti-HMGCR antibody positive immune-mediated necrotizing myopathy (HMGCR-IMNM) based on recent findings. Using advances in diagnostic modalities that can confirm the presence of anti-HMGCR antibody, the clinical and pathological manifestations of HMGCR-IMNM were found to be broader than previously reported. Although only a small percentage of HMGCR-IMNM patients present with atypical manifestations, some of these patients show slow disease progression and clinical symptoms, which are similar to those of limb-girdle muscular dystrophies. Other atypical HMGCR-IMNM patients have skin conditions similar to dermatomyositis-like skin rush or dermatological presentations of Jessner-Kanoff disease or cutaneous lymphoma, whose pathological changes including CD8-positive and bcl-2-positive lymphocytic accumulations, similar to Jessner-Kanoff lymphocytic infiltration of skin or low-grade cutaneous lymphoma, which are observed in muscle and skin. Anti-HMGCR autoantibodies define unique populations of IMNM patients. Recent studies have revealed that clinicopathological manifestations of HMGCR-IMNM, especially extramuscular symptoms and pathological manifestations, are more common than previously recognized.

Dermoscopic Patterns in Relation to the Clinicopathologic Manifestations of Leprosy

Objectives. Leprosy is a chronic granulomatous infection caused by the obligate intracellular organism Mycobacterium leprae. Current diagnostic tests for confirmation and treatment monitoring such as slit skin smear and biopsy are invasive and require time for processing, reading, and interpretation. Dermoscopy is a technique that allows the visualization of structures not readily seen by the naked eye. It can be performed at the point of care, providing a non-invasive link between clinical and histopathologic examination. This study aimed to determine the dermoscopic findings and associated clinicopathologic findings of the different forms of leprosy.&#x0D; Methods. A cross-sectional study was conducted. All new and follow-up patients aged 19 years old and above clinically diagnosed with leprosy were invited to participate in the study during the three-month investigation period. Clinical and dermoscopic photographs of representative skin lesions were taken, and a review of slit skin smear and histopathology results was done. Data analysis was performed using Stata SE version 13. The association between dermoscopic findings and the following parameters: anatomic location, Ridley-Jopling classification, WHO classification, treatment duration, and average bacteriologic index were analyzed using Fisher’s exact test. The level of significance was set at 5%.&#x0D; Results. A total of 57 lesions were included. Linear vessels (p=0.031), structureless areas (p=0.008), and globules (p=0.002) were found to be significantly associated with the anatomic location. Decreased hair was found to be significantly associated with treatment duration (p=0.038). No significant associations were found between dermoscopic findings and Ridley-Jopling classification, WHO classification, and ABI. Eight biopsies taken at the time of dermoscopy were reviewed, with all sites showing structureless or globular areas corresponding to the presence of granulomas on histopathology (100%). No other notable associations were observed.&#x0D; Conclusion. Dermoscopy is a potentially useful tool to aid in the diagnosis and treatment monitoring of leprosy. Limitations of this study include the small sample size, the preponderance of subjects in the lepromatous pole, and assessments by a single trained dermoscopist. A longer study duration including a larger number of newly diagnosed leprosy patients is recommended.

PIAS2-mediated blockade of IFN-\u03b2 signaling: a basis for sporadic Parkinson disease dementia

Familial Parkinson disease (PD) is associated with rare genetic mutations, but the etiology in most patients with sporadic (s)PD is largely unknown, and the basis for its progression to dementia (sPDD) is poorly characterized. We have identified that loss of IFNβ or IFNAR1, the receptor for IFNα/β, causes pathological and behavioral changes resembling PDD, prompting us to hypothesize that dysregulated genes in IFNβ-IFNAR signaling pathway predispose one to sPD. By transcriptomic analysis, we found defective neuronal IFNβ-IFNAR signaling, including particularly elevated PIAS2 associated with sPDD. With meta-analysis of GWASs, we identified sequence variants in IFNβ-IFNAR-related genes in sPD patients. Furthermore, sPDD patients expressed higher levels of PIAS2 mRNA and protein in neurons. To determine its function in brain, we overexpressed PIAS2 under a neuronal promoter, alone or with human α-synuclein, in the brains of mice, which caused motor and cognitive impairments and correlated with intraneuronal phosphorylated (p)α-synuclein accumulation and dopaminergic neuron loss. Ectopic expression of neuronal PIAS2 blocked mitophagy, increased the accumulation of senescent mitochondrial and oxidative stress, as evidenced by excessive oxDJ1 and 8OHdG, by inactivating ERK1/2-P53 signaling. Conversely, PIAS2 knockdown rescued the clinicopathological manifestations of PDD in Ifnb–/– mice on restoring mitochondrial homeostasis, oxidative stress, and pERK1/2-pP53 signaling. The regulation of JAK-STAT2-PIAS2 signaling was crucial for neurite outgrowth and neuronal survival and excitability and thus might prevent cognitive impairments. Our findings provide insights into the progression of sPD and dementia and have implications for new therapeutic approaches.

Brain Toxoplasmosis Comorbid with Autoimmune Disease: Complicated Immune Response And Case Demonstration

Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), commonly involving the brain. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of brain toxoplasmosis are linked to individual immune responses including brain infiltration of T-cells that are thought to fight against toxoplasmosis. In patients with autoimmune diseases, immune status is typically characterized by T-cell infiltration and complicated mainly by immunosuppressant and/or immunomodulatory treatment. In this study, we demonstrate clinical and radiological features correlated with pathological features of brain toxoplasmosis at different disease stages in a patient with coexisting autoimmune diseases, including systemic lupus erythematosus and autoimmune hepatitis. The infiltration of CD8+ T-cells in toxoplasma immunostaining-positive acute lesions was greater than that in toxoplasma immunostaining-negative chronic lesions. We also review previously reported cases of brain toxoplasmosis with comorbid autoimmune diseases. Our present case and literature review suggest that brain toxoplasmosis in patients with autoimmune diseases may be asymptomatic unless disease complications occur; it may present as an incidental finding at postmortem examination of rapidly developed lesions. T-cell infiltration in patients with autoimmune diseases and coexisting toxoplasmosis may be at least partially reduced; ultimately, the roles of T-cell infiltration in brain toxoplasmosis deserve further investigation.Learning ObjectivesDiscuss complicated immune response to toxoplasmosis in patients with autoimmune diseases.Describe clinical, radiological, and pathological features of brain toxoplasmosis in patients with autoimmune diseases.