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Purpose: Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. Methods: We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. Results: MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). Conclusions: Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis still represents a universal threat that creates a wider range of public and animal health impacts. One of the most important steps in the pathogenesis of this disease and granuloma formation is the phagocytosis of tuberculous bacilli by macrophages. Mycobacteria replicate in macrophages, which are crucial to the pathophysiology of mycobacterial infections; however, scarce information is available about the dynamics of the granuloma-stage immunological response. Therefore, immunohistochemistry was used in this work to evaluate the expression of CD68, iNOS, and HLA-DR in different stages of TB granulomas from naturally infected cattle with tuberculosis. Two thousand, one hundred and fifty slaughtered beef cattle were examined during the period from September 2020 to March 2022. Sixty of them showed gross tuberculous pulmonary lesions and samples were collected from all of them for histopathological examination, Ziehl-Neelsen (ZN) staining, and bacteriological culturing. Selected samples that yielded a positive result for ZN and mycobacterial culturing were subjected to an immunohistochemical study of CD68, iNOS, and HLA-DR expression by macrophages according to granuloma stages. Immunohistochemical analysis revealed that the immunolabeling of CD68+, iNOS+, and HLA-DR+ macrophages significantly reduced as the stage of granuloma increased from stage I to stage IV (P < 0.003, P < 0.002, and P < 0.002, respectively). The distribution of immunolabeled macrophages was similar for the three markers, with immunolabeled macrophages distributed throughout early-stage granulomas (I, II), and surrounding the necrotic core in late-stage granulomas (III, IV). Our results suggest a polarization to the pro-inflammatory environment and increased expression of CD68+, iNOS+, and HLA-DR+ macrophages in the early stages of granulomas (I, II), which may play a protective role in the immune response of naturally infected beef cattle with tuberculosis. [ABSTRACT FROM AUTHOR]

Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients' association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges. [ABSTRACT FROM AUTHOR]

Background: Two cases of orbitofrontal cholesterol granuloma masquerading as frontal sinus mucoceles were reported to understand image findings, clinical and histopathologic features of orbitofrontal cholesterol granuloma to improve its diagnosis and treatment. Case presentation: Two East Asian patients aged 41 and 27 without personal or familial medical or trauma history presented with the common complaint of proptosis and inferomedial displacement of the eyeballs. The computed tomography (CT) of both cases showed an irregularly shaped, well-defined lesion in the left frontal bone associated with bony erosion. The lesions resulted in the bone absorption of frontal bone and orbital roof, which extended into the superior orbital space. Anterior orbitotomy through subbrow incision by drainage and curettage resulted in a curative outcome. The histopathological examination revealed inflammatory granulation tissues, fibrous capsule wall, cholesterol clefts with altered blood pigments, and calcifications, consistent with the diagnosis of cholesterol granuloma. No recurrence was observed for one year after surgery in one case and three years in the other. Conclusions: When the following features are observed: orbital CT exhibits cystic lesion with irregular bone destruction in the superolateral orbit, magnetic resonance imaging (MRI) depicts lesions are hyperintense signals on T1 weighted images (T1WI), and T2 weighted images (T2WI), and the contrast-enhanced imaging reveals that the most of tumor is showed a non-significant enhancement, orbitofrontal cholesterol granuloma should be considered. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium avium subsp. paratuberculosis infected animals show a variety of granulomatous lesions, from focal forms with well-demarcated granulomas restricted to the gut-associated lymphoid tissue (GALT), that are seen in the initial phases or latency stages, to a diffuse granulomatous enteritis, with abundant (multibacillary) or scant (paucibacillary) bacteria, seen in clinical stages. Factors that determine the response to the infection, responsible for the occurrence of the different types of lesion, are still not fully determined. It has been seen that regulatory T cells (Treg) play an important role in various diseases where they act on the limitation of the immunopathology associated with the immune response. In the case of paratuberculosis (PTB) the role of Treg lymphocytes in the immunity against Map is far away to be completely understood; therefore, several studies addressing this subject have appeared recently. The aim of this work was to assess, by immunohistochemical methods, the presence of Foxp3+ T lymphocytes in intestinal samples with different types of lesions seen in cows with PTB. Methods: Intestinal samples of twenty cows showing the different pathological forms of PTB were evaluated: uninfected controls (n = 5), focal lesions (n = 5), diffuse paucibacillary (n = 5) and diffuse multibacillary (n = 5) forms. Foxp3+ lymphocyte distribution was assessed by differential cell count in intestinal lamina propria (LP), gut-associated lymphoid tissue (GALT) and mesenteric lymph node (MLN). Results: A significant increase in the number of Foxp3+ T cells was observed in infected animals with respect to control group, regardless of the type of lesion. However, when the different categories of lesion were analyzed independently, all individuals with PTB lesions showed an increase in the amount of Foxp3+ T lymphocytes compared to the control group but this increase was only significant in cows with focal lesions and, to a lesser extent, in animals with diffuse paucibacillary forms. The former showed the highest numbers, significantly different from those found in cows with diffuse lesions, where no differences were noted between the two forms. No specific distribution pattern was observed within the granulomatous lesions in any of the groups. Conclusions: The increase of Foxp3+ T cells in focal forms, that have been associated with latency or resistance to infection, suggest an anti-inflammatory action of these cells at these stages, helping to prevent exacerbation of the inflammatory response, as occurs in diffuse forms, responsible for the appearance of clinical signs. [ABSTRACT FROM AUTHOR]

Rationale: Patients with asthma who have neutrophilic bronchitis may have an underlying cause leading to increased susceptibility to airway infections. Methods: Retrospective review of patients with asthma who had a previous history of recurrent exacerbations that had been associated with airway or sinus infections referred to a tertiary asthma center between 2005 and 2020. Demographics, clinical features, and airway inflammation type determined by sputum cytometry were compared between CFTR carriers and non-carriers. Multiple linear regression was used to identify clinical predictors of CFTR carrier status. Response to nebulized hypertonic saline was assessed by comparing the number of infective exacerbations before and after its initiation. Results: 75 patients underwent CFTR mutation testing. Of these, 13 (17%) were CFTR carriers. The most common mutation was Δ F508. CFTR carriers were older (adjusted odds ratio 1.06 (CI 95% 1.01, 1.13)) and had more frequent flares requiring hospitalization (4.19 (1.34, 24.74)). Neutrophilic airway inflammation was the most common inflammatory subtype in CFTR carriers, though 8/13 also had eosinophilic bronchitis. Nebulized hypertonic saline was well tolerated by most and reduced the frequency of infective exacerbations. Conclusions: The prevalence of CFTR heterozygosity in this cohort with recurrent neutrophilic bronchitis is higher than in the general population. Respiratory disease in CFTR carriers is associated with older age and may cause significant morbidity. Airway neutrophilia is the most common inflammatory subtype, but > 50% had eosinophilic bronchitis requiring treatment. Hypertonic saline appears to be well tolerated and effective in reducing the number of infective exacerbations. [ABSTRACT FROM AUTHOR]

Background: Microwave ablation (MWA) is a popular therapy for liver malignant tumor in recent years. Few studies have been conducted on its use in the treatment of hepatic alveolar echinococcosis (HAE). The study aims to evaluate the efficacy and safety of MWA in the treatment of HAE. Methods: This study analyzed the data of 45 patients (mean age, 38 ± 2 years; 24 males) diagnosed with HAE and underwent MWA treatment between June 2014 to December 2019. The patients after MWA were examined by CT or MRI [follow-up: 32 months (IQR 23–48.5)] to determine whether the lesions were relapsed and to evaluate the therapeutic effect of MWA. The safety of MWA was evaluated by monitoring postoperative complications. Clinical data, such as patient demographics, imaging features of the lesions, relevant findings of laboratory tests before and after ablation, and information related to ablation, were collected and analyzed. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare relevant laboratory indicators before and after MWA. Results: MWA was applied to 57 HAE lesions in 45 patients. The median size of lesions was 3.42 cm (IQR2.85–4.41). The rate of complete ablation was 100% (57/57). The median follow-up time was 32 months (IQR 23–48.5). The recurrence rate was 13% (6/45), and the median time of recurrence was 22 months. The rate of minor complications was 11.1% (5/45), and there were no major complications and deaths. Compared to preoperative, ALB, RBC, HBG, and PLT were decreased (p < 0.001); ALT, TB, DB, and WBC were increased (p < 0.001); and no statistically difference in PT, APTT, and INR (p > 0.05). Conclusions: MWA might be a safe and effective way to cure HAE. Meanwhile, it provides a new option and a new way of thinking about treatment for patients with HAE. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare imaging features between COVID-19 and mycoplasma pneumonia (MP). Materials and methods: The data of patients with mild COVID-19 and MP who underwent chest computed tomography (CT) examination from February 1, 2020 to April 17, 2020 were retrospectively analyzed. The Pneumonia-CT-LKM-PP model based on a deep learning algorithm was used to automatically quantify the number, volume, and involved lobes of pulmonary lesions, and longitudinal changes in quantitative parameters were assessed in three CT follow-ups. Results: A total of 10 patients with mild COVID-19 and 13 patients with MP were included in this study. There was no difference in lymphocyte counts at baseline between the two groups (1.43 ± 0.45 vs. 1.44 ± 0.50, p = 0.279). C-reactive protein levels were significantly higher in MP group than in COVID-19 group (p < 0.05). The number, volume, and involved lobes of pulmonary lesions reached a peak in 7–14 days in the COVID-19 group, but there was no peak or declining trend over time in the MP group (p < 0.05). Conclusion: Based on the longitudinal changes of quantitative CT, pulmonary lesions peaked at 7–14 days in patients with COVID-19, and this may be useful to distinguish COVID-19 from MP and evaluate curative effects and prognosis. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis.Methods: Building on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis.Discussion: The current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities. Trial Registration The trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936. [ABSTRACT FROM AUTHOR]

Background: With widespread clinical application of imaging techniques, renal space-occupying lesions have been identified at an increasing frequency. Here, we report two rare cases, Castleman disease (CD) and IgG4-related disease (IgG4-RD), presenting primarily with the symptoms and imaging findings of kidney malignancy. Case presentation: In case 1, an occupying lesion located in the right renal pelvis was detected using magnetic resonance imaging in a 32-year-old female who presented with hematuria and lumbago. First misdiagnosed as carcinoma of the renal pelvis, the patient underwent right radical nephroureterectomy. However, postoperative pathological and immunohistochemistry studies finally confirmed the diagnosis of CD. In case 2, a 45-year-old male presented with the chief complaint of anuria. Nephrostomy and renal biopsy indicated lymphoma, following which, antegrade urography and computed tomography urography were performed, which revealed bilateral hydronephrosis and mass lesions around the renal pelvis. Partial resection of the masses and frozen section examination indicated the diagnosis of CD. However, the results of postoperative histopathology and immunohistochemistry combined with serum IgG4 were consistent with IgG4-RD. Both the patients recovered well after drug treatment without recurrence of the diseases. Conclusions: Inflammatory pseudotumor of CD and IgG4-RD with kidney involvement are primarily diagnosed by postoperative histopathology and can pose a preoperative diagnostic challenge because these lesions can masquerade as kidney malignancy. Therefore, we recommend core biopsy as a nonnegligible procedure to evaluate renal masses and potentially prevent unnecessary surgical treatment. [ABSTRACT FROM AUTHOR]

Background: Percutaneous needle biopsy of renal masses has been increasingly utilized to aid the diagnosis and guide management. It is generally considered as a safe procedure. However, tumor seeding along the needle tract, one of the complications, theoretically poses potential risk of tumor spread by seeded malignant cells. Prior studies on the frequency of needle tract seeding in renal tumor biopsies are limited and clinical significance of biopsy-associated tumor seeding remains largely controversial. Methods: Here we investigated the frequencies of biopsy needle tract tumor seeding at our institution by reviewing the histology of renal cell carcinoma nephrectomy specimens with a prior biopsy within the last seventeen years. Biopsy site changes were recognized as a combination of foreign body reaction, hemosiderin deposition, fibrosis and fat necrosis. The histologic evidence of needle tract tumor seeding was identified as clusters of tumor cells embedded in perinephric tissue spatially associated with the biopsy site. In addition, association between parameters of biopsy techniques and tumor seeding were investigated. Results: We observed needle tract tumor seeding to perinephric tissue in six out of ninety-eight (6 %) renal cell carcinoma cases including clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe, and clear cell papillary renal cell carcinoma. The needle tract tumor seeding was exclusively observed in papillary renal cell carcinomas (6/28, 21 %) that were unifocal, small-sized (≤ 4 cm), confined to the kidney and had type 1 features. No recurrence or metastasis was observed in the papillary renal cell carcinoma cases with tumor seeding or the stage-matched cases without tumor seeding. Conclusions: Our study demonstrated a higher than reported frequency of needle tract tumor seeding. Effective communication between pathologists and clinicians as well as documentation of tumor seeding is recommended. Further studies with a larger patient cohort and longer follow up to evaluate the impact of needle tract tumor seeding on long term prognosis are needed. This may also help reach a consensus on appropriate pathologic staging of renal cell carcinoma when the only site of perinephric fat invasion is within a biopsy needle tract. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus retinitis (CMVR) is an important opportunistic infection (OI) occurring mainly in patients with acquired immunodeficiency syndrome (AIDS) and has the potential to cause severe visual impairment and blindness among AIDS patients. Subsequent to the adoption and implementation of widespread antiretroviral therapy (ART), the prognosis of AIDS-associated CMVR has been substantially improved. Nevertheless, the equivocal clinical evidence as regards the optimal timing for ART initiation in patients with an established CMVR diagnosis is required. We therefore designed the present study in order to investigate the optimal timing for ART initiation in AIDS/CMVR patients.Methods: This will be a prospective, randomized controlled trial to be performed at 17 hospitals in mainland China. A total of 300 participants with CMVR will be randomly assigned to an early ART initiation group (ART initiation within 2 weeks after anti-CMV therapy), or a deferred ART initiation group (initiation of ART more than 2 weeks after anti-CMV therapy) at a 1:1 ratio. All participants will receive 48 weeks of follow-up after anti-CMV therapy initiation. Our primary outcome will be the incidence of visual loss (to a visual acuity worse than 20/40 or 20/200) in the two groups during the 48-week follow-up period. Secondary outcomes will include changes in HIV virological suppression and serum CD4+ T-cell counts, the incidence of mortality, retinitis progression (movement of the peripheral border of a CMV lesion ≥ ½ disc diameter, or occurrence of a new CMV lesion), retinal detachment, immune recovery uveitis (IRU), and other OIs and adverse events between the two study groups during the 48 weeks of follow-up.Discussion: The study aims to investigate the optimal timing for ART initiation in AIDS/CMVR patients. We hope to be able to extract robust clinical evidence for use in optimal AIDS/CMVR management should our trial be successful.Trial Registration: This research was registered as one of the twelve clinical trials under the name of a general project "A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections", ChiCTR1900021195. Registered on 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 . [ABSTRACT FROM AUTHOR]

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA.Case Presentation: A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl.Conclusions: The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation. [ABSTRACT FROM AUTHOR]

Background: Histiocytic sarcoma (HS) is a rare neoplasm showing morphological and immunophenotypic features of mature tissue histiocytes. We report a patient with nodal HS exhibiting prominent reactive eosinophilic infiltration. Case presentation: A 68-year-old man presented with intermittent left lower abdominal pain and weight loss over 3 months. A computed tomography scan revealed multiple abdominal nodules. Open biopsy of the mesenteric tumors was performed for definitive diagnosis. Histologically, the tumor was comprised of a diffuse noncohesive proliferation of pleomorphic large cells, including multinucleated cells. Neoplastic cells were positive for histiocytic markers (CD68, CD163, and LIGHT) and PD-L1 but lacked markers of Langerhans cells, follicular dendritic cells, and epithelial cells. Frequent reactive inflammatory cells were intermingled in the background. Interestingly, prominent eosinophilic infiltration was also noted. Spindle neoplastic cells were prone to be present around areas with little to no eosinophilic infiltration and exhibiting fibrosis and lymphatic vessel proliferation. Conversely, polygonal neoplastic cells were prone to be present around areas with relatively large amounts of eosinophilic infiltration without fibrosis or lymphatic vessel proliferation. Immunohistochemically, the tumor cells and reactive eosinophils expressed eotaxin-2 and eotaxin-3, respectively. Conclusion: We revealed that eotaxins induced the selective migration of eosinophils into tissues in this case. These eosinophils may affect the tumor remodeling and tumor biology characteristics of HS, such as fibrosis and lymphatic vessel proliferation. [ABSTRACT FROM AUTHOR]

Background: Actinobaculum suis is a bacterium known to cause infections of the urogenital tract of sows. Infection can occur through close contact to boars, who frequently carry the pathogen in their preputial diverticulum but do not become clinically diseased themselves. In the current case, Actinobaculum suis was isolated from pyogranuloma of inflamed epididymis in a boar with poor fertility. Case presentation: Increased return to oestrus rate, which worsened after the purchase of a new boar, was reported in an organic farm in Switzerland. During herd examination, azoospermia of the boar was diagnosed, and slaughter, followed by examination of its urogenital tract, was carried out. Pathologically, pyogranuloma formation and epididymitis were diagnosed. Bacteriology of the pyogranulomas showed growth of Actinobaculum suis and mixed flora. After the boar was replaced, the return to oestrus rate improved tremendously. Conclusion: A close relative of Actinobaculum suis, namely Actinotignum schaalii, has already been associated with epididymitis in humans. Considering the present case and the parallels in human medicine, Actinobaculum suis should be included in the list of differentials of boars with poor fertility. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied.Case Presentation: A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up.Conclusions: We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade. [ABSTRACT FROM AUTHOR]

Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3-6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12-48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA. [ABSTRACT FROM AUTHOR]

Background: Epstein–Barr virus (EBV) is associated with the pathogenesis of a variety of malignancies, most notably lymphomas. Especially in the background of immunodeficiency, such as primary immunodeficiency disorder (PID) and post-transplant lymphoproliferative disorder (PTLD), the role of EBV might be crucial. PIDs are rare heterogeneous diseases affecting the development and/or the function of the innate and adaptive immune system. Malignancy is the second-highest cause of death after infection, and lymphoma accounts for about half of malignancies. The most frequently reported lymphoma type is diffuse large B-cell lymphoma (DLBCL) and the incidence of T-cell lymphoma is rare. PTLDs are also rare serious lymphoid and/or plasmacytic proliferative disorders that occur after undergoing solid organ or hematopoietic stem cell transplantation (HSCT). In the context of HSCT, most reported PTLDs have occurred in patients who received allogenic HSCT, but only a few cases have been reported in autologous HSCT (AutoHSCT) recipients. Case presentation: A 53-year-old female patient initially presented with enlargement of the left cervical lymph nodes and was diagnosed with EBV-positive DLBCL. She was treated with R-CHOP, R-ACES, and AutoHSCT and went into remission. Four years later, computed tomography results revealed multiple lung nodules and abnormal infiltration, and sustained and progressing hypogammaglobulinemia was observed. The pathological specimen of video-assisted thoracoscopic surgical lung biopsy demonstrated extensive invasion of lymphocytes with notable granuloma findings. Flow cytometric immunophenotyping analysis showed that lymphocytes were positive for CD3 and CD5; especially, CD3 was expressed in the cytoplasm. Southern blot analysis revealed rearrangements of the T-cell receptor Cβ1 gene. She was diagnosed with peripheral T-cell lymphoma, not otherwise specified, accompanied by notable granulomatous lesions. Conclusion: Here, as a unique case of metachronous B-cell and T-cell lymphoma, we report a rare case of T-cell lymphoma that mainly affected the lungs with the presentation of notable granulomatous findings following AutoHSCT for EBV-positive DLBCL at the age of 53 years. These lung lesions of granulomatous T-cell lymphoma could be related to the underlying primary immunodeficiency background associated with sustained hypogammaglobulinemia. [ABSTRACT FROM AUTHOR]

Majocchi's granuloma is an uncommon fungal infection of the dermis and subcutaneous tissue. The most frequently identified cause of Majocchi's granuloma is anthropophilic Trichophyton rubrum, and it is most commonly located on the anterior aspect of the lower limbs in women. Here, we report a case of Majocchi's granuloma on the forearm, a site that is rarely involved, in a 62-year-old woman who had been bitten by a dog. Histological examination revealed a dense dermal infiltrate composed of lymphoplasmacytic cells and neutrophils, with hyphae in the dermis. The presence of the fungus, Trichophyton tonsurans, was confirmed by mycological examination and molecular methods. Therefore, histological and mycological examination confirmed the diagnosis of Majocchi's granuloma. The patient was treated with local moxibustion and itraconazole, 200 mg/day, for 60 days, which facilitated a complete resolution of the lesions. [ABSTRACT FROM AUTHOR]

Background: ETV6-ACSL6 is a fusion gene rarely reported in myeloid malignancies, and its clinical characteristics, proper treatment strategies, and effect on prognosis are poorly understood.Results: Sixteen patients with the ETV6-ACSL6 fusion gene were identified, with a median age of 50 years. Twelve patients were male. Clinical diagnoses included chronic eosinophilic leukemia, not otherwise specified, acute myeloid leukemia, and other types of myeloproliferative and myelodysplastic disorders. Ten out of 12 patients had increased levels of eosinophils, and four out of five had increased levels of basophils in peripheral blood. Treatment with tyrosine kinase inhibitors was ineffective. The prognosis of the patients was poor, with seven patients dying within 1 year.Conclusions: Patients with the ETV6-ACSL6 fusion gene mainly present with myeloproliferative and myelodysplastic disorders, typically with increased eosinophils and/or basophils and poor survival. Intensive therapies such as allogenic stem cell transplantation should be an initial consideration for eligible patients. [ABSTRACT FROM AUTHOR]

Background: The outbreak of a novel coronavirus since December 2019, became an emergency of major international concern. As of June 21, 2020, the SARS-CoV-2 pandemic has caused 8,769,844 confirmed infections with 463,745 fatal cases worldwide. The SARS-CoV-2 outbreak is a major challenge for clinicians. In our clinic, we found a rare case that a COVID-19 patient combined with ischemic stroke. Case presentation: A 79-year-old man was admitted to the Hubei Provincial Hospital of Traditional Chinese Medicine due to right limb weakness for 1 day and slight cough for 1 week. At presentation, his oxygen saturation was 94.2% on room air and body temperature was 37.3 °C (99.0 °F) with some moist rales. Neurological examination showed right limb weakness, and the limb muscle strength was grade 4. The left leg and arms were unaffected. In addition, runs of speech were not fluent enough with tongue deviation. Laboratory studies showed lymphopenia and eosinophilic granulocytopenia. Chest CT revealed bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, with a peripheral lung distribution. Real-time polymerase chain reaction (RT-PCR) from throat swab sample was positive for SARS-CoV-2 nucleic acid. This patient was treated with antiviral drugs and anti-inflammatory drugs with supportive care until his discharge. Clopidogrel (75 mg) and atorvastatin (20 mg) were administered orally to treat acute ischemic stroke. After 12 days of treatment, he can walk normally and communicate with near fluent language. Conclusion: We report an even more unusual case, a patient who was hospitalized for right limb weakness and was later diagnosed with COVID-19. Here, SARS-CoV-2 infection caused hypoxemia and excessive secretion of inflammatory cytokines, which contribute to the occurrence and development of ischemic stroke. Once COVID-19 patients show acute ischemic stroke, neurologists should cooperate with infectious disease doctors to help patients. [ABSTRACT FROM AUTHOR]

Background: Intracranial necrotizing granulomatous space-occupying lesions are sparsely reported in literature. Variability in presenting symptomatology and radiographic features makes diagnostic work-up difficult.Case Presentation: This report presents the case of a 77-year-old female with sinusitis and fatigue who underwent an MRI revealing a posterior fossa lesion compressing the fourth ventricle. Subsequent contrast CT of the chest, abdomen, and pelvis was negative for primary malignancy. Histopathologic examination of the lesion following biopsy showed it to be a necrotizing granuloma in an antineutrophil cytoplasmic antibody (ANCA) negative patient. The most likely diagnosis was determined to be spontaneous necrotizing granuloma, a rare entity with only one previous report noted.Conclusions: Spontaneous necrotizing granuloma of the CNS is a rare entity that represents an important differential consideration in the work-up of space occupying lesions of the CNS. [ABSTRACT FROM AUTHOR]

Background: Chondromesenchymal hamartoma of the chest wall is a rare, benign disease that usually presents at birth or in early infancy. It typically involves one or more ribs, forming a unilateral or bilateral extrapleural mass. Patients may be asymptomatic or complain of mild respiratory distress depending on tumor size and location. To the best of our knowledge, only two of the approximately 100 cases reported so far are adults. Case presentation: We present two cases of chondromesenchymal hamartoma. The first case involved the left fifth rib in a 24-year-old male, in close proximity to the fifth vertebral body in the left posterior mediastinum, mimicking a posterior mediastinal tumor on imaging. The tumor was excised via thoracoscopy and the patient had an uneventful postoperative course. The second case was that of a 5-month-old boy, who had a tumor involving the left fifth and sixth ribs which caused thoracic cage collapse. Following en bloc resection of the tumor and the involved rib segments, the patient was transferred to the intensive care unit for treatment of pulmonary infection and disseminated intravascular coagulation (DIC). He was discharged from the hospital in stable condition 11 days later. On histopathology, the tumor was found to be a chondromesenchymal hamartoma with immature spindle-shaped mesenchymal cells, plate-like hyaline cartilage, areas of woven bone formation, endochondral ossification and calcification, osteoclastic giant cells, and secondary aneurysmal bone cysts. Conclusions: Although the presently reported cases have morphological characteristics similar to previously reported ones, they had distinct radiological and clinical characteristics. Patient 1 is only the third report of an adult with chondromesenchymal hamartoma. His case was characterized by its radiological appearance mimicking a posterior mediastinal tumor. Patient 2 represents the first documentation of DIC as a postoperative complication following excision of a chondromesenchymal hamartoma. We present these two cases to provide clinicopathological insights regarding this extremely rare tumor that are relevant to both pathologists and clinicians. [ABSTRACT FROM AUTHOR]

Peripheral metastases of glioblastoma (GBM) are very rare despite the ability of GBM cells to pass through the blood-brain barrier and be disseminated through the peripheral blood. Here, we describe a detailed genetic and immunological characterization of a GBM metastasis in the skeleton, which occurred during anti-PD-1 immune checkpoint therapy. We performed whole genome sequencing (WGS) and 850 K methylation profiling of the primary and recurrent intracranial GBM as well as one of the bone metastases. Copy number alterations (CNA) and mutational profiles were compared to known genomic alterations in the TCGA data base. In addition, immunophenotyping of the peripheral blood was performed. The patient who was primarily diagnosed with IDH-wildtype GBM. After the resection of the first recurrence, progressive intracranial re-growth was again detected, and chemotherapy was replaced by PD-1 checkpoint inhibition, which led to a complete intracranial remission. Two months later MR-imaging revealed multiple osseous lesions. Biopsy confirmed the GBM origin of the skeleton metastases. Immunophenotyping reflected the effective activation of a peripheral T-cell response, with, however, increase of regulatory T cells during disease progression. WGS sequencing demonstrated distinct genomic alterations of the GBM metastasis, with gains along chromosomes 3 and 9 and losses along chromosome 4, 10, and 11. Mutational analysis showed mutations in potentially immunologically relevant regions. Additionally, we correlated tumour-infiltrating lymphocyte and microglia presence to the occurrence of circulating tumour cells (CTCs) in a larger cohort and found a decreased infiltration of cytotoxic T cells in patients positive for CTCs. This study exemplifies that the tumour microenvironment may dictate the response to immune checkpoint therapy. In addition, our study highlights the fact that despite an effective control of intracranial GBM, certain tumour clones have the ability to evade the tumour-specific T-cell response and cause progression even outside of the CNS. [ABSTRACT FROM AUTHOR]

Background: An intravenous leiomyomatosis is a special type of uterine leiomyoma characterized by the formation of benign leiomyomatous tissue within the vascular wall. Although histologically benign, intracardiac metastasis can lead to circulatory failure, and death, if untreated. Herein, we report on a case of a uterine intravenous leiomyomatosis with an isolated large adherent metastasis in the right atrium of the heart. Case Presentation: A 52-year-old Japanese woman sought medical attention at our hospital for lower abdominal pain. A 27-cm uterine mass was detected on clinical imaging, with a 78 × 47-mm mass in the right atrium detected on preoperative echocardiography. Intracardiac mass resection and tricuspid annuloplasty were performed as the first-stage surgery. The pedicle of the tumor was adherent to the wall of the atrium. On histological examination, the tumor was found to consist of spindle-shaped cells with eosinophilic cytoplasm, without atypia, but with a myxoid change, and rich microvascularization of the pedicle. Total abdominal hysterectomy was performed as the second-stage surgery, with confirmation of the diagnosis as uterine intravenous leiomyomatosis with an isolated metastasic lesion to the right atrium. There has been no evidence of tumor recurrence in the 15 months since surgery. Conclusion: We report a unique case in which a large right atrial leiomyoma was identified following a uterine intravenous leiomyomatosis. Our case exemplifies that intravenous leiomyomatosis metastatic tumors have the potential to grow via their vascularization. [ABSTRACT FROM AUTHOR]

Background: Interpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions. Methods: Search for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above. Results: Most clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL. Conclusions: P63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL. [ABSTRACT FROM AUTHOR]

Background: In 1951 Churg and Strauss first described the clinical condition now known as eosinophilic granulomatosis with polyangiitis (EGPA), characterized by asthma, nasal polyposis, rhinosinusitis, hypereosinophilia with organ infiltration, and necrotizing vasculitis. It is classified as an antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, but ANCA negativity is common and more frequently encountered in EGPA with myocardial involvement. Long-term survival has substantially improved with corticosteroid treatment but myocardial involvement is still the leading cause of death in EGPA.Case Presentation: A 53-year old man with a history of asthma and nasal polyposis presented with acute chest pain and elevated troponin; a percutaneous coronary intervention was performed. The left ventricle was described as hypertrophic. After 20 days the myocardium had markedly increased in thickness of both the right and left ventricle. Evaluation revealed hypereosinophilia in the blood and nasal mucosal tissue, which confirmed the diagnosis of EGPA. He presented with signs of active vasculitis including weight loss, tiredness, intracerebral hemorrhage, and increasing serum creatinine. After 6 days of corticosteroid treatment, the myocardium returned to its initial thickness.Conclusion: Rapid and marked thickening of the myocardium is not frequently reported but may occur in EGPA. Myocardial thickening in EGPA can be quickly reversed by corticosteroids, and is most likely caused by edema. [ABSTRACT FROM AUTHOR]

Background: Pythiosis is a potentially fatal but non-contagious disease affecting humans and animals living in tropical and subtropical climates, but is also reasonably widespread in temperate climates, throughout the world. The most commonly reported affected animal species with pythiosis are equine and canine, with fewer cases in bovine and feline. Extracutaneous infections caused by Pythium insidiosum have been rarely described in the cat. Case presentation: Sublingual pythiosis was diagnosed in a 2-year-old, male, Domestic Shorthair cat. The cat had a multilobulated, sublingual mass present for 3 months. Histopathological examination revealed severe multifocal coalescing eosinophilic granulomatous inflammation. Centers of the inflammation contained hyphae that were 3-7 μm-wide, non-parallel, uncommonly septate and rarely branching. The fungal-like organism was identified as P. insidiosum by polymerase chain reaction and subsequent amplicon sequencing. Conclusions: Only a few feline pythiosis cases have been reported and, when encountered, it usually causes granulomatous diseases of the skin or gastrointestinal tract. This case presents an unusual manifestation of feline pythiosis, representing the first involving the oral cavity in cats or dogs. [ABSTRACT FROM AUTHOR]

Background: Kimura's disease (KD; eosinophilic granuloma of soft tissue) is an inflammatory granulomatous disorder of unknown cause with eosinophilic infiltration that occurs mainly in soft tissue. KD occurs mainly in the head and neck, but development in the axillary region is very rare.Case Presentation: A 74-year-old Japanese woman was evaluated for a mass that she noted in the left axillary region. On physical examination, there was a palpable, thumb-sized, hard, elastic, freely movable mass in the left axilla. Blood tests showed elevated soluble interleukin-2 receptor (sIL-2R), normal serum immunoglobulin (Ig) G4, and elevated serum IgE. Ultrasonography of the left axilla showed multiple lymph nodes (LNs) with irregular margins in which central hyperechogenicity was lost. A systemic search by computed tomography (CT) showed no systemic lymphadenopathy or other mass-like lesions suspicious for a primary tumour other than in the left axillary LNs. Biopsy of an excised LN was performed under local anaesthesia for a definitive diagnosis. Histopathology showed various-sized lymphoid follicles, large nodular lesions with an enlarged mantle zone, multiple various-sized germinal centres in single nodules, and eosinophilic infiltration between the nodes. Immunohistochemical (IHC) staining of the germinal centres was positive for cluster of differentiation (CD) 10, positive for B-cell lymphoma (bcl)-6, and negative for bcl-2. These findings led to a diagnosis of KD. Ultrasound after 3 months of follow-up showed disappearance of the axillary lymphadenopathy.Conclusions: A very rare case of KD in the axillary LNs was described. KD has the potential to occur in any region. [ABSTRACT FROM AUTHOR]

Background: Various therapeutic approaches have been proposed for the treatment of pediatric patients with eosinophilic granuloma (EG) of the cervical spine. Our aim was to discuss and present our experience with the individualized surgical intervention of pediatric cervical EG complicated with neurologic deficits and/or spinal instability. Methods: We retrospectively analyzed the clinical data of 19 children who were diagnosed with cervical EG comor spinal/or spinal instability (evaluated by the Spinal Instability Neoplastic Score, SINS = 7) and treated surgically in our institution. Results: Lesions involved C1-2 in 7 patients and C3-7 in 12 patients. Anterior tumor resection combined with posterior pedicle screw fixation, anterior approach of excision and instrumentation, and posterior tumor resection combined with pedicle screws instrumentation were selected according to the different locations of tumors. Frankel scale and Oucher scale improved significantly after surgery. There was no morphologic alteration of the neck at follow-up. Conclusions: Surgery can significantly improve the neurologic status and symptoms. Surgical decision-making must be individually tailored to minimize the influence of surgery on spine growth. [ABSTRACT FROM AUTHOR]

Background: The clinic-pathological features and outcomes of Chinese patients with antineutrophil cytoplasmic autoantibody (ANCA)-positive eosinophilic granulomatosis with polyangiitis (EGPA) and renal involvement have not been studied.Methods: Fourteen EGPA patients with renal involvement were included. All patients underwent renal biopsy. Clinic-pathological features and outcomes were retrospectively analyzed.Results: The most common initial symptom of EGPA was asthma (57.1 %), followed by hemoptysis (21.4 %), gross hematuria (14.3 %), and arthritis (7.1 %). All patients had positive serum ANCA (anti-MPO in 12, anti-PR3 in 2). Elevated eosinophils (median 15 %, range 10-45 %) were found in all patients. The median serum IgE level was 463 g/L (range 200-1000 g/L). All patients presented with renal dysfunction, with a median SCr of 5.4 mg/dL (range 1.47-11 mg/dL), seven patients (50 %) required initial renal replacement therapy. Thirteen patients showed hematuria and proteinuria (median 1.1 g/24 h, range 0.5-7.8 g/24 h). Renal biopsy showed pauci-immune segmental necrotizing glomerulonephritis with crescents in 13 patients and acute interstitial nephritis in one patient. Twelve patients (85.7 %) showed renal interstitial eosinophil infiltration, among whom three had eosinophilic granuloma. Among seven patients (71.4 %) who required initial dialysis, 5 discontinued dialysis, one died, one received maintenance dialysis after glucocorticoids plus immunosuppressive for induction treatment. Twelve patients were followed up for a median of 43.5 months (range 6-83 months), during follow-up, two patients progressed to end-stage renal disease, nine had chronic kidney disease with eGFR < 60 mL/min, and two patients had normal eGFR.Conclusions: Renal involvement in ANCA-positive EGPA could be severe and showed varied renal histology. Although intensive immunosuppressive therapy effectively improved the renal function, the long-term renal survival was poor. Early diagnosis and treatment are essential to improve long-term renal survival. [ABSTRACT FROM AUTHOR]

Background: Langerhans cell histiocytosis (LCH), previously known as Histiocytosis X, is an infrequent disease that congregates a wide spectrum of clinical presentations with variable systemic involvement. Unification of these diseases under only one category is based on the almost identical histopathologic features of the lesions, but the etiology and proper approach for each presentation remains controversial. The localized alternative of Langerhans cell histiocytosis (LLCH), known as Eosinophilic Granuloma (EG) of bone, is the predominant clinical presentation of LCH. The maxilla is involved in 1 % of the head and neck region cases, representing an uncommon condition in this area. Case Presentation: In this clinical case report, it is described a case of a 16-year-old male patient with an asymptomatic osteolytic lesion at first upper left molar apical level, a finding detected on control radiographic images was reported as "Monostotic Eosinophilic granuloma of the maxillary bone", which was later confirmed through an incisional biopsy. A surgical excision was initially planned, but finally it was not performed due to a spontaneous healing of the lesion after the incisional biopsy. Conclusions: The presented case supports a conservative approach in the management of solitary EG of maxillary and mandibular bone lesions and even supports an expectant attitude in the course of treatment given the possibility of a spontaneous regression after the biopsy, especially in small lesions. [ABSTRACT FROM AUTHOR]

Background Eosinophilic granulomatosis with polyangiitis is a complex multisystemic syndrome with heterogeneous presentation. Most often, there is a clinical history of asthma or other atopic conditions, and current presentation generally includes signs of cutaneous or pulmonary involvement. Very few reports described myalgia or weakness as the chief complaint. Of these, only a few included muscle biopsy evaluation and none showed convincing evidence of primary myositis. We believe this report is the first to demonstrate true myositis in the setting of early eosinophilic granulomatosis with polyangiitis. Case presentation This report describes a 74 year old Caucasian man, with no known allergies, presenting severe myalgia, muscle weakness, jaw claudication, and fever. Blood work showed marked eosinophilia and high creatine kinase levels. Biceps brachialis muscle biopsy revealed eosinophilic necrotizing vasculitis and true myositis with myophagocytosis of non-necrotic fibers and strong sarcolemmal MHC-1 overexpression by immunohistochemistry. This patient was successfully treated with prednisone and azathioprine. Conclusion Our finding of true myositis in a case of eosinophilic granulomatosis with polyangiitis suggests that primary auto-immunity against muscle fibers, distinct from the secondary effects of vasculitis, can occur in this entity and may represent an overlap syndrome. Early recognition of eosinophilic granulomatosis with polyangiitis in patients presenting with myositis may provide an opportunity to treat the vasculitis before onset of severe multisystemic disease. We recommend the use of muscle biopsy with immunohistochemistry for MHC-1 to confirm the diagnosis of myositis in the setting of eosinophilic granulomatosis with polyangiitis. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic granulomatosis with polyangiitis is a rare, necrotizing systemic vasculitis associated with asthma and hypereosinophilia. Its cause and pathophysiology are still being elucidated.Case Presentation: We report a case of eosinophilic granulomatosis with polyangiitis in a 50-year-old Caucasian woman who presented with chest pain, dyspnea at rest, fever, and periorbital swelling. She was found to have significant hypereosinophilia and cardiac tamponade physiology. A biopsy confirmed extensive infiltration of both lungs and pericardium by eosinophils. She did not have any anti-neutrophil cytoplasmic antibodies.Conclusions: Eosinophilic granulomatosis with polyangiitis diagnosis does not require the presence of anti-neutrophil cytoplasmic antibodies. Anti-neutrophil cytoplasmic antibody-positive and anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis may present with different clinical phenotypes, perhaps suggesting two distinct disease etiologies and distinct pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Hepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma japonicum infection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweed Fucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary. Methods: We evaluated the hepatic pathology from S. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in the S. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detected in vitro. Furthermore, macrophages were treated with fucoidan in vitro and to detect the inflammatory cytokines. Results: Treatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response during S. japonicum infection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) were observed in the livers from fucoidan-treated S. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treated S. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-β were dramatically increased in the livers from S. japonicum-infected mice after fucoidan treatment. Furthermore, in vitro stimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages. Conclusions: These findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress of S. japonicum infection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection. [ABSTRACT FROM AUTHOR]

Objective: Acute tubular necrosis (ATN) is a frequent cause of acute kidney injury (AKI). In patients with nephrotic syndrome (NS), AKI demands the differential diagnosis between ATN and rapidly progressive glomerulonephritis. In some cases, conclusive diagnosis is possible only by kidney biopsy. We aimed to study the potential use of urine cytology in the differential diagnosis between ATN and proliferative glomerular lesion in patients with NS. Results: Cell size analysis showed a higher proportion of small cells and a lower proportion of large cells in the urine of patients with AKI. Cells phenotypes were easily defined using cytological preparations. Leukocytes were found to be a primary classifier of NS groups, with higher number in patients with AKI and patients with proliferative glomerular lesions. Although renal biopsy is still required for confirmative diagnosis, our data suggests that urinary cytology can be readily performed and support the differential diagnosis between proliferative glomerular lesion and ATN in patients with NS and AKI. [ABSTRACT FROM AUTHOR]

Background: Heart disease (HD) is the major cause of morbidity and mortality in patients with hypereosinophilic diseases. Due to a lack of adequate animal models, our understanding of the pathophysiology of eosinophil-mediated diseases with heart complications is limited. We have discovered a mouse mutant, now maintained on an A/J inbred background, that spontaneously develops hypereosinophilia in multiple organs. Cellular infiltration into the heart causes an eosinophilic myocarditis, with affected mice of the mutant line (i.e., A/JHD) demonstrating extensive myocardial damage and remodeling that leads to HD and premature death, usually by 15-weeks old. Results: Maintaining the A/JHD line for many generations established that the HD trait was heritable and implied the mode of inheritance was not too complex. Backcross and intercross populations generated from mating A/JHD males with females from four different inbred strains produced recombinant populations with highly variable rates of affected offspring, ranging from none in C57BL/6 J intercrosses, to a few mice with HD using 129S1/SvImJ intercrosses and C57BL/6 J backcrosses, but nearly 8% of intercrosses and > 17% of backcrosses from SJL/J related populations developed HD. Linkage analyses of these SJL/J derived recombinants identified three highly significant loci: a recessive locus mapping to distal chromosome 5 (LOD = 4.88; named Emhd1 for eosinophilic myocarditis to heart disease-1); and two dominant variants mapping to chromosome 17, one (Emhd2; LOD = 7.51) proximal to the major histocompatibility complex, and a second (Emhd3; LOD = 6.89) that includes the major histocompatibility region. Haplotype analysis identified the specific crossovers that defined the Emhd1 (2.65 Mb), Emhd2 (8.46 Mb) and Emhd3 (14.59 Mb) intervals. Conclusions: These results indicate the HD trait in this mutant mouse model of eosinophilic myocarditis is oligogenic with variable penetrance, due to multiple segregating variants and possibly additional genetic or nongenetic factors. The A/JHD mouse model represents a unique and valuable resource to understand the interplay of causal factors that underlie the pathology of this newly discovered eosinophil-associated disease with cardiac complications. [ABSTRACT FROM AUTHOR]

Background: Atypical manifestations, such as elevated serum immunoglobulin-G4 (IgG4) and extra-pulmonary IgG4 positive plasmacyte infiltration, have been described in patients with eosinophilic granulomatosis with polyangiitis (EGPA), such complicated situation might not be readily differentiated from IgG4-related disease.Case Presentation: Here, we report an interesting and rare case of EGPA in a 41 year-old male with negative anti-neutrophil cytoplasmic antibodies (ANCAs), which showed abundant pulmonary IgG4-positive plasma cells infiltration and markedly elevated serum IgG4 levels without extra-pulmonary lesions of IgG4-related disease. The clinical characteristics hesitated us whether the diagnosis as EGPA overlapping with IgG4-related lung disease should be concluded because of the absence of storiform fibrosis and obliterative phlebitis with lymphoplasmacytic infiltration. The patient's systemic symptoms, pulmonary lesions, blood eosinophils count / percentage, and serum IgG4 levels were significantly improved with immunosuppressive therapy.Conclusions: We consider that the overlapping pathogenesis exists in the disease course of EGPA and IgG4-related disease, which may lead to interaction during the course of the diseases. And the utilization of diagnostic criteria for IgG4-related lung disease with the careful differentiation is needed in such cases. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis in children. A delayed or missed diagnosis of pediatric EGPA is common, owing to the atypical clinical manifestation and limited recognition of this disorder. The vasculitis in EGPA typically involves small to medium size vessels. Extensive occlusion of arteries in the extremities was being extremely rare and has never been reported in children. Case presentation: A 10-year and 10-month-old girl with recurrent wheezing and breathlessness during exercise, was initially diagnosed with asthma at the age of five years. Despite unexplained manifestations, including intermittent remarkably increased eosinophilia, uncontrolled allergic rhinitis, and recurrent petechia, from the onset of asthma through to its remission, the consideration of EGPA was completely ignored until the patient presented with aggravated petechia and severe ulceration of the lower extremities, associated with extensive stenosis and/or occlusion of the arteries of the shank and foot. Given her history of asthma, eosinophilia, allergic rhinitis, mononeuropathy, pulmonary infiltrates, and vasculitis confirmed by the skin biopsy, the diagnosis of EGPA was ultimately confirmed. Regrettably, the initial inappropriate and irrational use of corticosteroid failed to relieve the symptoms until more aggressive treatment with intravenous methylprednisolone was started. This was followed by methotrexate treatment, with tapering of prednisone, without relapse over a six-month follow-up. Conclusions: Pediatric rheumatologists should be alert to the possibility of EGPA in children with refractory asthma associated with unexplained manifestations, and should be aware of the thromboembolic complications as vascular sequelae of EGPA. [ABSTRACT FROM AUTHOR]

Background: Langerhans cell histiocytosis previously known as histiocytosis X is a rare disease of children and young adults with a very broad clinical spectrum. In children, its annual incidence is estimated between 0.2-0.5 per 100,000.Case Representation: An 8-year-old Moroccan girl with no known personal or family history presented to our institution with painful swelling of both forearms. An X-ray and magnetic resonance imaging were inconclusive. We then performed a biopsy curettage (of her left forearm). Microscopic analysis followed by immunohistochemical analysis disclosed a diagnosis of Langerhans cell histiocytosis. No chemotherapy was necessary. Clinical and radiological improvement was achieved after 6 months.Conclusion: The particularity of this observation is the bilaterality of the lesion on both forearms and it has not previously been reported. Langerhans cell histiocytosis should be included in the differential diagnosis of osteomyelitis and Ewing's sarcoma. [ABSTRACT FROM AUTHOR]

Background: Granulomatosis with polyangiitis (GPA) is a systemic ANCA-associated vasculitis characterized by necrotizing granulomatous inflammation and a predilection for the upper and lower respiratory tract. Eosinophilic granulomatosis with polyangiitis (EGPA) is also a systemic ANCA-associated vasculitis, but EGPA is characterized by eosinophilic as well as granulomatous inflammation and is more commonly associated with asthma and eosinophilia. Polyangiitis overlap syndrome is defined as systemic vasculitis that does not fit precisely into a single category of classical vasculitis classification and/or overlaps with more than one category. Several polyangiitis overlap syndromes have been identified, however, there are very few case reports of an overlap syndrome involving both GPA and EGPA in the medical literature.Case Presentation: We conducted a PUBMED literature review using key words 'granulomatosis with polyangiitis,' 'Wegener's,' 'GPA,' 'eosinophilic granulomatosis with polyangiitis,' 'Churg-Strauss,' 'EGPA,' 'overlap syndrome,' 'Wegener's with eosinophilia,' and 'GPA with eosinophilia' in English only journals from 1986 to 2017. Relevant case reports and review articles of overlap syndromes of GPA and EGPA were identified. We aim to report a unique case of GPA and EGPA overlap syndrome and review the cases that have been previously described. Between 1986 and 2017, we identified 15 cases that represent an overlap syndrome with compelling features of both GPA and EGPA. Patients ranged in age between 21 and 78. Of those whose gender was identified, 80 % of the patients were female. All cases described involved the lungs, 60 % reported sinus involvement, and more than 50 % displayed renal involvement. An overwhelming majority of patients were positive for c-ANCA and demonstrated eosinophilia (peripheral blood or tissue eosinophilia). A preponderance of the cases described were treated with systemic corticosteroids combined with an immunosuppressive/cytotoxic agents.Conclusion: To our knowledge, there have been very few cases reported of an overlap syndrome of GPA and EGPA. Identification of patients with a polyangiitis overlap syndrome of GPA and EGPA is imperative as prognosis, longitudinal management and treatment modalities may differ between these entities. [ABSTRACT FROM AUTHOR]

Background: Kimura's disease (KD; eosinophilic granuloma of soft tissue) is an inflammatory granulomatous disorder of unknown cause with eosinophilic infiltration that occurs mainly in soft tissue. KD occurs mainly in the head and neck, but development in the axillary region is very rare., Case Presentation: A 74-year-old Japanese woman was evaluated for a mass that she noted in the left axillary region. On physical examination, there was a palpable, thumb-sized, hard, elastic, freely movable mass in the left axilla. Blood tests showed elevated soluble interleukin-2 receptor (sIL-2R), normal serum immunoglobulin (Ig) G4, and elevated serum IgE. Ultrasonography of the left axilla showed multiple lymph nodes (LNs) with irregular margins in which central hyperechogenicity was lost. A systemic search by computed tomography (CT) showed no systemic lymphadenopathy or other mass-like lesions suspicious for a primary tumour other than in the left axillary LNs. Biopsy of an excised LN was performed under local anaesthesia for a definitive diagnosis. Histopathology showed various-sized lymphoid follicles, large nodular lesions with an enlarged mantle zone, multiple various-sized germinal centres in single nodules, and eosinophilic infiltration between the nodes. Immunohistochemical (IHC) staining of the germinal centres was positive for cluster of differentiation (CD) 10, positive for B-cell lymphoma (bcl)-6, and negative for bcl-2. These findings led to a diagnosis of KD. Ultrasound after 3 months of follow-up showed disappearance of the axillary lymphadenopathy., Conclusions: A very rare case of KD in the axillary LNs was described. KD has the potential to occur in any region.

Background: Various therapeutic approaches have been proposed for the treatment of pediatric patients with eosinophilic granuloma (EG) of the cervical spine. Our aim was to discuss and present our experience with the individualized surgical intervention of pediatric cervical EG complicated with neurologic deficits and/or spinal instability., Methods: We retrospectively analyzed the clinical data of 19 children who were diagnosed with cervical EG comor spinal/or spinal instability (evaluated by the Spinal Instability Neoplastic Score, SINS ≥ 7) and treated surgically in our institution., Results: Lesions involved C1-2 in 7 patients and C3-7 in 12 patients. Anterior tumor resection combined with posterior pedicle screw fixation, anterior approach of excision and instrumentation, and posterior tumor resection combined with pedicle screws instrumentation were selected according to the different locations of tumors. Frankel scale and Oucher scale improved significantly after surgery. There was no morphologic alteration of the neck at follow-up., Conclusions: Surgery can significantly improve the neurologic status and symptoms. Surgical decision-making must be individually tailored to minimize the influence of surgery on spine growth.

Cases of canine neural angiostrongylosis (NA) with cerebrospinal fluid (CSF) evaluations in the peer-reviewed literature were tabulated. All cases were from Australia. A retrospective cohort of 59 dogs was contrasted with a series of 22 new cases where NA was diagnosed by the presence of both eosinophilic pleocytosis and anti-Angiostrongylus cantonensis immunloglobulins (IgG) in CSF, determined by ELISA or Western blot. Both cohorts were drawn from south east Queensland and Sydney. The retrospective cohort comprised mostly pups presented for hind limb weakness with hyperaesthesia, a mixture of upper motor neurone (UMN) and lower motor neurone (LMN) signs in the hind limbs and urinary incontinence. Signs were attributed to larval migration through peripheral nerves, nerve roots, spinal cord and brain associated with an ascending eosinophilic meningo-encephomyelitis. The contemporary cohort consisted of a mixture of pups, young adult and mature dogs, with a wider range of signs including (i) paraparesis/proprioceptive ataxia (ii) lumbar and tail base hyperaesthesia, (iii) multi-focal central nervous system dysfunction, or (iv) focal disease with neck pain, cranial neuropathy and altered mentation. Cases were seen throughout the year, most between April and July (inclusive). There was a preponderance of large breeds. Often littermates, or multiple animals from the same kennel, were affected simultaneously or sequentially. A presumptive diagnosis was based on consistent signs, proximity to rats, ingestion/chewing of slugs or snails and eosinophilic pleocytosis. NA was diagnosed by demonstrating anti-A. cantonensis IgG in CSF. Detecting anti-A. cantonensis IgG in serum was unhelpful because many normal dogs (20/21 pound dogs; 8/22 of a hospital population) had such antibodies, often at substantial titres. Most NA cases in the contemporary series (19/22) and many pups (16/38) in the retrospective cohort were managed successfully using high doses of prednisolone and opioids. Treatment often included antibiotics administered in case protozoan encephalomyelitis or translocated bacterial meningitis was present. Supportive measures included bladder care and physiotherapy. Several dogs were left with permanent neural deficits. Dogs are an important sentinel species for NA. Human cases and numerous cases in tawny frogmouths were reported from the same regions as affected dogs over the study period. [ABSTRACT FROM AUTHOR]