Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

Osteoid osteoma of the distal radius presenting as an inconspicuous swelling in a young child.

Osteoid osteoma is a benign osteoblastic tumour with a predilection for the lower extremity that rarely affects the forearm. It is commonly seen in adolescents and young adults, and is seldom diagnosed in the paediatric age group. We report a boy in his early childhood who presented with a swelling over the distal forearm, which was incidentally noted by the mother 3 months ago. Plain radiographs showed diffuse sclerosis of the dorsal cortex of the distal radius. CT scan showed a central lucent nidus in the intramedullary region and surrounding sclerosis in the radial metaphysis, confirming the diagnosis of osteoid osteoma. The patient was successfully treated by surgical en bloc resection of the nidus and was asymptomatic at 1-year follow-up. Non-specific symptoms at presentation make it a challenge to diagnose osteoid osteoma in children and it needs to be considered in the differential diagnosis when radiographs show lytic lesions in the bone.

Deletion of podocyte Rho-associated, coiled-coil-containing protein kinase 2 protects mice from focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) shares podocyte damage as an essential pathological finding. Several mechanisms underlying podocyte injury have been proposed, but many important questions remain. Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) is a serine/threonine kinase responsible for a wide array of cellular functions. We found that ROCK2 is activated in podocytes of adriamycin (ADR)-induced FSGS mice and cultured podocytes stimulated with ADR. Conditional knockout mice in which the ROCK2 gene was selectively disrupted in podocytes (PR2KO) were resistant to albuminuria, glomerular sclerosis, and podocyte damage induced by ADR injection. In addition, pharmacological intervention for ROCK2 significantly ameliorated podocyte loss and kidney sclerosis in a murine model of FSGS by abrogating profibrotic factors. RNA sequencing of podocytes treated with a ROCK2 inhibitor proved that ROCK2 is a cyclic nucleotide signaling pathway regulator. Our study highlights the potential utility of ROCK2 inhibition as a therapeutic option for FSGS.

Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy. METHODS: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy. Participants were subdivided based on histopathology of the resected brain. Paired blood- and brain-derived DNA samples were sequenced using high-coverage targeted next generation sequencing to high depth (585× and 1360×, respectively). Variants were identified using Genome Analysis ToolKit (GATK4) MuTect-2 and confirmed using high-coverage Amplicon-EZ sequencing. RESULTS: Sequence data on 41 patients passed quality control. Four somatic variants were validated following amplicon sequencing: within CBL, ALG13, MTOR, and FLNA. The diagnostic yield across 41 patients was 10%, 9% in mesial temporal lobe epilepsy with hippocampal sclerosis and 20% in malformations of cortical development. SIGNIFICANCE: This study provides novel insights into the etiology of mesial temporal lobe epilepsy with hippocampal sclerosis, highlighting a potential pathogenic role of somatic variants in CBL and ALG13. We also report candidate diagnostic somatic variants in FLNA in focal cortical dysplasia, while providing further insight into the importance of MTOR and related genes in focal cortical dysplasia. This work demonstrates the potential molecular diagnostic value of variants in both germline and somatic epilepsy genes.

Mapping hippocampal and thalamic atrophy in epilepsy: A 7-T magnetic resonance imaging study.

OBJECTIVE: Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data-driven alternative for grouping of patients. In this work, we leverage ultra-high-field 7-T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug-resistant focal epilepsy. METHODS: Forty-two drug-resistant epilepsy patients and 13 controls with 7-T structural neuroimaging were included in this study. We measured hippocampal subfield and thalamic nuclei volumetry, and applied an unsupervised machine learning algorithm, Latent Dirichlet Allocation (LDA), to estimate atrophy patterns across the hippocampal subfields and thalamic nuclei of patients. We studied the association between predefined clinical groups and the estimated atrophy patterns. Additionally, we used hierarchical clustering on the LDA factors to group patients in a data-driven approach. RESULTS: In patients with mesial temporal sclerosis (MTS), we found a significant decrease in volume across all ipsilateral hippocampal subfields (false discovery rate-corrected p [pFDR] < .01) as well as in some ipsilateral (pFDR < .05) and contralateral (pFDR < .01) thalamic nuclei. In left temporal lobe epilepsy (L-TLE) we saw ipsilateral hippocampal and some bilateral thalamic atrophy (pFDR < .05), whereas in right temporal lobe epilepsy (R-TLE) extensive bilateral hippocampal and thalamic atrophy was observed (pFDR < .05). Atrophy factors demonstrated that our MTS cohort had two atrophy phenotypes: one that affected the ipsilateral hippocampus and one that affected the ipsilateral hippocampus and bilateral anterior thalamus. Atrophy factors demonstrated posterior thalamic atrophy in R-TLE, whereas an anterior thalamic atrophy pattern was more common in L-TLE. Finally, hierarchical clustering of atrophy patterns recapitulated clusters with homogeneous clinical properties. SIGNIFICANCE: Leveraging 7-T MRI, we demonstrate widespread hippocampal and thalamic atrophy in epilepsy. Through unsupervised machine learning, we demonstrate patterns of volumetric atrophy that vary depending on disease subtype. Incorporating these atrophy patterns into clinical practice could help better stratify patients to surgical treatments and specific device implantation strategies.

Current advances in rodent drug-resistant temporal lobe epilepsy models: Hints from laboratory studies.

Anti-seizure drugs (ASDs) are the first choice for the treatment of epilepsy, but there is still one-third of patients with epilepsy (PWEs) who are resistant to two or more appropriately chosen ASDs, named drug-resistant epilepsy (DRE). Temporal lobe epilepsy (TLE), a common type of epilepsy usually associated with hippocampal sclerosis (HS), shares the highest proportion of drug resistance (approximately 70%). In view of the key role of the temporal lobe in memory, emotion, and other physiological functions, patients with drug-resistant temporal lobe epilepsy (DR-TLE) are often accompanied by serious complications, and surgical procedures also yield extra considerations. The exact mechanisms for the genesis of DR-TLE remain unillustrated, which makes it hard to manage patients with DR-TLE in clinical practice. Animal models of DR-TLE play an irreplaceable role in both understanding the mechanism and searching for new therapeutic strategies or drugs. In this review article, we systematically summarized different types of current DR-TLE models, and then recent advances in mechanism investigations obtained in these models were presented, especially with the development of advanced experimental techniques and tools. We are deeply encouraged that novel strategies show great therapeutic potential in those DR-TLE models. Based on the big steps reached from the bench, a new light has been shed on the precise management of DR-TLE.

Clinical, Histologic, and Transcriptomic Evaluation of Sequential Fat Grafting for Morphea: A Nonrandomized Controlled Trial.

Importance: Morphea is a rare disease of unknown etiology without satisfactory treatment for skin sclerosis and soft tissue atrophy. Objective: To provide clinical, histologic, and transcriptome evidence of the antisclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction gel (SVF gel) for morphea. Design, Setting, and Participants: This single-center, nonrandomized controlled trial was conducted between January 2022 and March 2023 in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University and included adult participants with early-onset or late-onset morphea who presented with varying degrees of skin sclerosis and soft tissue defect. Interventions: Group 1 received sequential grafting of fresh fat and cryopreserved SVF gel (at 1 and 2 months postoperation). Group 2 received single autologous fat grafting. All patients were included in a 12-month follow-up. Main Outcome and Measures: The primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores as evaluated by 2 independent blinded dermatologists. The histologic and transcriptome changes of morphea skin lesions were also evaluated. Results: Of 44 patients (median [IQR] age, 26 [23-33] years; 36 women [81.8%]) enrolled, 24 (54.5%) were assigned to group 1 and 20 (45.5%) to group 2. No serious adverse events were noted. The mean (SD) mLoSSI scores at 12 months showed a 1.6 (1.50) decrease in group 1 and 0.9 (1.46) in group 2 (P = .13), whereas the mean (SD) LoSDI scores at 12 months showed a 4.3 (1.34) decrease in group 1 and 2.1 (1.07) in group 2 (P < .001), indicating that group 1 had more significant improvement in morphea skin damage but not disease activity compared with group 2. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in group 1, whereas skin biopsy specimens of group 2 patients did not show significant change. Transcriptome analysis of skin biopsy specimens from group 1 patients suggested that tumor necrosis factor α signaling via NFκB might contribute to the immunosuppressive and antifibrotic effect of sequential fat grafting. A total of 15 hub genes were captured, among which many associated with morphea pathogenesis were downregulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF. Conclusions and Relevance: The results of this nonrandomized trial suggest that sequential fat grafting with fresh fat and cryopreserved SVF gel was safe and its therapeutic effect was superior to that of single autologous fat grafting with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effectiveness after treatment. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2200058003.

FIB-4 liver fibrosis index correlates with aortic valve sclerosis in non-alcoholic population.

AIM: Hepatic fibrosis, a progressive scarring of liver tissue, is commonly caused by non-alcoholic fatty liver disease (NAFLD), which increases the risk of cardiovascular disease. The Fibrosis-4 (FIB-4) index is a non-invasive tool used to assess liver fibrosis in patients with NAFLD. Aortic valve sclerosis (AVS), a degenerative disorder characterized by thickening and calcification of valve leaflets, is prevalent in the elderly and associated with increased cardiovascular morbidity and mortality. Recent studies have suggested that AVS may also be linked to other systemic diseases such as liver fibrosis. This study aimed to investigate the relationship between the FIB-4 index and AVS in a non-alcoholic population, with the hypothesis that the FIB-4 index could serve as a potential marker for AVS. METHOD: A total of 92 patients were included in this study. AVS was detected using transthoracic echocardiography, and patients were divided into groups according to the presence of AVS. The FIB-4 index was calculated for all patients and compared between the groups. RESULTS: A total of 17 (18.4%) patients were diagnosed AVS. Patients with AVS had higher rates of diabetes mellitus, older age, hypertension, angiotensin-converting enzyme inhibitor use, higher systolic blood pressure (BP) and diastolic BP in the office, coronary artery disease prevalence, left atrial volume index (LAVI), left ventricular mass index (LVMI), and late diastolic peak flow velocity (A) compared to those without AVS. Moreover, AVS patients had significantly higher creatinine levels and lower estimated glomerular filtration rate. Remarkably, the FIB-4 index was significantly higher in patients with AVS. In univariate and multivariate analyses, higher systolic BP in the office (OR, 1.044; 95% CI 1.002-1.080, p = .024) and higher FIB-4 index (1.46 ± .6 vs. .91 ± .46, p < .001) were independently associated with AVS. CONCLUSION: Our findings suggest that the FIB-4 index is associated with AVS in non-alcoholic individuals. Our results highlight the potential utility of the FIB-4 index as a non-invasive tool for identifying individuals at an increased risk of developing AVS.

Association Between Aortic Valve Sclerosis and Clonal Hematopoiesis of Indeterminate Potential.

Background: The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. Methods: Participants with AVS (valves ≥2 mm thick, high echogenicity, and a peak transaortic velocity of <2.5 m/sec) and an age- and sex-matched control group were enrolled. Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics. Results: From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6±8.5 yrs, and 54.5% were male. An average of 1.3 CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of ≥0.5%, was similar between the groups. However, the AVS group had larger CHIP clones: 49 (39.2%) participants had a VAF of ≥1% (vs. 13 [21.0%] in the control group; P=0.020), and 25 (20.0%) had a VAF of ≥2% (vs. 4 [6.5%]; P=0.028). AVS is independently associated with a VAF of ≥1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11-5.36; P=0.027). This trend was concordant and clearer in the IPTW cohort. Conclusions: Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.

A case of rapidly progressive glomerulonephritis with double-positive anti-GBM antibody and MPO-ANCA after SARS-CoV-2 vaccination and relapse during 1 year follow-up.

Although mRNA vaccines for COVID-19 are highly beneficial and are recommended for patients with kidney disease, adverse reactions in some patients after vaccination have been problematic. Various vasculitis and renal disorders have been reported after vaccination; however, a causal relationship has not yet been identified. In this report, we describe a case of rapidly progressive glomerulonephritis that developed after SARS-CoV-2 vaccination, in which both anti-glomerular basement membrane (anti-GBM) and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were present. The patient's renal biopsy showed that of the 48 glomeruli in total, four showed global sclerosis and none showed segmental sclerosis. The biopsy showed 11 cellular glomerular crescents and 5 fibrocellular glomerular crescents. Renal function improved with steroids, rituximab, and plasma exchange. Approximately 9 months later, MPO-ANCA was again elevated, and the pulmonary lesions worsened, again requiring multidisciplinary treatment. This case suggests that caution should be exercised in the development of double-positive disease after vaccination, and that long-term observation may be necessary because of the possibility of relapse.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.

Quantifying refractive error in companion dogs with and without nuclear sclerosis: 229 eyes from 118 dogs.

OBJECTIVE: To evaluate the relationship between nuclear sclerosis (NS) and refractive error in companion dogs. ANIMALS STUDIED: One hundred and eighteen companion dogs. PROCEDURES: Dogs were examined and found to be free of significant ocular abnormalities aside from NS. NS was graded from 0 (absent) to 3 (severe) using a scale developed by the investigators. Manual refraction was performed. The effect of NS grade on refractive error was measured using a linear mixed effects analysis adjusted for age. The proportion of eyes with >1.5 D myopia in each NS grade was evaluated using a chi-square test. Visual impairment score (VIS) was obtained for a subset of dogs and compared against age, refractive error, and NS grade. RESULTS: Age was strongly correlated with NS grade (p < .0001). Age-adjusted analysis of NS grade relative to refraction showed a mild but not statistically significant increase in myopia with increasing NS grade, with eyes with grade 3 NS averaging 0.58-0.88 D greater myopia than eyes without NS. However, the myopia of >1.5 D was documented in 4/58 (6.9%) eyes with grade 0 NS, 12/91 (13.2%) eyes with grade 1 NS, 13/57 (22.8%) eyes with grade 2 NS, and 7/23 (30.4%) eyes with grade 3 NS. Risk of myopia >1.5 D was significantly associated with increasing NS grade (p = .02). VIS was associated weakly with refractive error, moderately with age, and significantly with NS grade. CONCLUSIONS: NS is associated with visual deficits in some dogs but is only weakly associated with myopia. More work is needed to characterize vision in aging dogs.

Long-term follow-up of severe autosomal recessive SP7-related bone disorder.

The SP7 gene encodes a zinc finger transcription factor (Osterix), which is a member of the Sp subfamily of sequence-specific DNA-binding proteins, playing an important role in osteoblast differentiation and maturation. SP7 pathogenic variants have been described in association with different allelic disorders. Monoallelic or biallelic SP7 variants cause Osteogenesis imperfecta type XII (OI12), a very rare condition characterized by recurrent fractures, skeletal deformities, undertubulation of long bones, hearing loss, no dentinogenesis imperfecta, and white sclerae. Monoallelic or biallelic SP7 variants may also cause sclerotic skeletal dysplasias (SSD), partially overlapping with Juvenile Paget's disease and craniodiaphyseal dysplasia, characterized by skull hyperostosis, long bones sclerosis, large ribs and clavicles, and possible recurrent fractures. Here, we report the long-term follow-up of an 85-year-old woman presenting with a complex bone disorder including features of either OI12 (bone fragility with multiple fractures, severe deformities and short stature) or SSD (striking skull hyperostosis with optic atrophy, very large ribs and clavicles and long bones sclerosis). Exome sequencing showed previously undescribed biallelic loss of function variants in the SP7 gene: NM_001173467.2(SP7): c.359_362del, p.(Asp120Valfs*11); NM_001173467.2(SP7): c.1163_1174delinsT, p.(Pro388Leufs*33). RT-qPCR confirmed a severely reduced SP7 transcription compared to controls. Our report provides new insights into the clinical and molecular features and long-term outcome of SP7-related bone disorders (SP7-BD), suggesting a continuum phenotypic spectrum characterized by bone fragility, undertubulation of long bones, scoliosis, and very heterogeneous bone mineral density ranging from osteoporosis to osteosclerosis.

Whole-Blood Transcriptome Unveils Altered Immune Response in Acute Myocardial Infarction Patients With Aortic Valve Sclerosis.

BACKGROUND: Aortic valve sclerosis (AVSc) presents similar pathogenetic mechanisms to coronary artery disease and is associated with short- and long-term mortality in patients with coronary artery disease. Evidence of AVSc-specific pathophysiological traits in acute myocardial infarction (AMI) is currently lacking. Thus, we aimed to identify a blood-based transcriptional signature that could differentiate AVSc from no-AVSc patients during AMI. METHODS: Whole-blood transcriptome of AVSc (n=44) and no-AVSc (n=66) patients with AMI was assessed by RNA sequencing on hospital admission. Feature selection, differential expression, and enrichment analyses were performed to identify gene expression patterns discriminating AVSc from no-AVSc and infer functional associations. Multivariable Cox regression analysis was used to estimate the hazard ratios of cardiovascular events in AVSc versus no-AVSc patients. RESULTS: This cross-sectional study identified a panel of 100 informative genes capable of distinguishing AVSc from no-AVSc patients with 94% accuracy. Further analysis revealed significant mean differences in 143 genes, of which 30 genes withstood correction for age and previous AMI or coronary interventions. Functional inference unveiled a significant association between AVSc and key biological processes, including acute inflammatory responses, type I IFN (interferon) response, platelet activation, and hemostasis. Notably, patients with AMI with AVSc exhibited a significantly higher incidence of adverse cardiovascular events during a 10-year follow-up period, with a full adjusted hazard ratio of 2.4 (95% CI, 1.3-4.5). CONCLUSIONS: Our findings shed light on the molecular mechanisms underlying AVSc and provide potential prognostic insights for patients with AMI with AVSc. During AMI, patients with AVSc showed increased type I IFN (interferon) response and earlier adverse cardiovascular outcomes. Novel pharmacological therapies aiming at limiting type I IFN response during or immediately after AMI might improve poor cardiovascular outcomes of patients with AMI with AVSc.

Generalized early inflammatory morphea mimicking interstitial T-cell lymphoma: A diagnostic pitfall.

Early generalized morphea can clinically mimic mycosis fungoides. The microscopic features of early inflammatory morphea may show variable degrees of infiltration and do not have the characteristic dermal collagen sclerosis. We report the case of a 63-year-old female patient who presented with a 2-month history of an asymptomatic skin rash. Physical examination revealed multiple erythematous to dusky patches on the trunk and thighs, resembling the patch stage of mycosis fungoides. Two skin biopsies were performed, both of which showed prominent interstitial lymphoid infiltration in the reticular dermis without dermal sclerosis. Small lymphocyte exocytosis and lining along the dermal-epidermal junction were observed focally in the epidermis. Small clusters of plasma cells and eosinophils were observed in perivascular areas. Although no predominant clonality was found for CD4 and CD8 stains, 50% loss of CD5 antigen and 90% loss of CD7 antigen expression were apparent in immunohistochemical studies. Subsequent blood tests showed a normal blood cell count and positive human T-lymphotropic virus Type 1 antibodies. The overall findings suggested interstitial mycosis fungoides or early adult T-cell lymphoma-leukemia. The patient refused aggressive treatment, and 3 months later, she presented with indurated plaques from the previous rash. A repeat biopsy revealed the typical features of morphea. This report discussed the pitfalls in the clinical and histopathological diagnosis of early generalized inflammatory morphea that both clinicians and pathologists should consider.

Automatic estimation of brain parenchymal fraction in patients with multple sclerosis: a comparison between synthetic MRI and an established automated brain segmentation software based on FSL.

PURPOSE: We aimed to validate the estimation of the brain parenchymal fraction (BPF) in patients with multiple sclerosis (MS) using synthetic magnetic resonance imaging (SyMRI) by comparison with software tools of the FMRIB Software Library (FSL). In addition to a cross-sectional method comparison, longitudinal volume changes were assessed to further elucidate the suitability of SyMRI for quantification of disease-specific changes. METHODS: MRI data from 216 patients with MS and 28 control participants were included for volume estimation by SyMRI and FSL-SIENAX. Moreover, longitudinal data from 35 patients with MS were used to compare registration-based percentage brain volume changes estimated using FSL-SIENA to difference-based calculations of volume changes using SyMRI. RESULTS: We observed strong correlations of estimated brain volumes between the two methods. While SyMRI overestimated grey matter and BPF compared to FSL-SIENAX, indicating a systematic bias, there was excellent agreement according to intra-class correlation coefficients for grey matter and good agreement for BPF and white matter. Bland-Altman plots suggested that the inter-method differences in BPF were smaller in patients with brain atrophy compared to those without atrophy. Longitudinal analyses revealed a tendency for higher atrophy rates for SyMRI than for SIENA, but SyMRI had a robust correlation and a good agreement with SIENA. CONCLUSION: In summary, BPF based on data from SyMRI and FSL-SIENAX is not directly transferable because an overestimation and higher variability of SyMRI values were observed. However, the consistency and correlations between the two methods were satisfactory, and SyMRI was suitable to quantify disease-specific atrophy in MS.

Spectrum of renal vascular lesions among patients with lupus nephritis: An experience from a tertiary care center.

Background: Lupus nephritis (LN) is the assemblage of glomerular, tubulointerstitial and vascular changes. Despite the fact that glomerular changes are overemphasized in pathological classification and scoring system, but the existence of vascular damage negatively impact the clinical course. Aims and Objective: This study was conducted to determine the clinicopathological spectrum of renal vascular lesions in lupus nephritis. Materials and Methods: Renal microvascular lesions in biopsy proven lupus nephritis were classified into 5 major categories-thrombotic microangiopathy, true vasculitis; lupus vasculopathy, uncomplicated vascular immune deposits, and arterial. Clinical details, laboratory parameters and histopathological variables were compared among all groups. Summary of chronic changes was also assessed. Results: Biopsies from 56 patients revealed thrombotic microangiopathy (2), lupus vasculopathy (3), uncomplicated vascular immune deposit (6), PAN type vasculitis (1) and arterial sclerosis (13). No renal vascular lesions were found in 35.18% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older Nephritis subtype. Activity indices were higher in lupus vasculopathy group whereas patients with arteriosclerosis showed highest chronicity index. Conclusions: Renal vascular lesions are common in systemic lupus erythematosus patients with nephritis and may be associated with aggressive clinical course.