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Langerhans cell histiocytosis comprises a heterogeneous range of clinical manifestations secondary to clonal proliferation of histiocytes, characterized by the accumulation of these cells in various organs and tissues. The ophthalmological component commonly involved is the orbit. Herein, we report a rare case of Langerhans cell histiocytosis with eyelid involvement, which resulted in severe ocular surface complications, which subsequently significantly impacted the patient’s quality of life. This case report highlights the fact that despite being rare, Langerhans cell histiocytosis should be included in the differential diagnosis of eyelid lesions. Furthermore, a multidisciplinary approach with a systemic overview is crucial for managing the ocular complications. [ABSTRACT FROM AUTHOR]

Background: Histiocytoses, including Langerhans cell histiocytosis (LCH), comprise a diverse group of histiocytic disorders characterized by the abnormal accumulation and proliferation of histiocytes in various tissues or organs throughout the body, ranging from benign, self-limited conditions to aggressive malignancies and systemic inflammatory syndromes. These lesions present unique diagnostic challenges due to their broad spectrum of clinical presentations, overlapping histopathological and immunophenotypical features, and genetic complexity. Methods: This review analyzes major histiocytic lesions, focusing on their epidemiology, clinical presentations, histologic and immunophenotypic features, and genetic characteristics to facilitate accurate diagnosis and differentiation among these histiocytoses. Results: LCH, a well-recognized lesion, can affect various organ systems and necessitates differentiation from other types of histiocytoses such as Erdheim-Chester disease (ECD), Rosai-Dorfman-Destombes disease (RDD), and cutaneous and mucocutaneous non-Langerhans cell histiocytoses. Some histiocytic lesions, such as histiocytic sarcoma, are inherently malignant, while others, like hemophagocytic lymphohistiocytosis (HLH), manifest as severe, potentially life-threatening systemic inflammatory syndromes. Recent molecular genetic studies revealed recurrent genetic alterations in the MAPK pathway, such as BRAF V600E and MAP2K1 in LCH and ECD, and KRAS, NRAS, and MAP2K1 mutations in a subset of RDD. Malignant histiocytoses frequently show alterations in tumor suppressor genes like TP53 and CDKN2A. Conclusion: Precise classification of histiocytic lesions relies on a comprehensive diagnostic approach that integrates clinical, histologic, immunophenotypic, and genetic data. Recent genetic advances shed light on these conditions' unique but occasionally overlapping pathogenic mechanisms. Molecular genetics advancements continue to refine diagnostic accuracy and present new therapeutic targets, especially for aggressive or treatment-resistant cases. [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease (ECD) is a rare clonal myeloid neoplasm typically affecting adults over 50 years old, with bone lesions in almost all patients. The prognosis is poor in most cases if left untreated. Clinical manifestations are not specific, which hinders early diagnosis. The disease has distinct radiological features. However, three-phase bone scintigraphy exhibits the most typical pattern of all imaging modalities, which is the prominent strikingly symmetrical radiotracer uptake in the distal ends of the femurs and proximal and distal ends of the tibiae, sparing the epiphyses. We report a case of a 54-year-old female patient, presenting with atypical persistent knee joint pain. After an MRI scan, she underwent a three-phase bone scan, revealing the characteristic pattern, thus indicating a possible ECD diagnosis, which was eventually confirmed in biopsy material. Novel aspects of the pathophysiology and treatment of the disease, as well as a differential diagnosis from the perspective of an MSK radiologist and nuclear medicine physician, are also discussed. [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease (ECD) is an exceedingly rare non-Langerhans cell CD68+ CD1a- S100- histiocytic multi-organ disease. Diagnosis of ECD is often delayed due to non-specific radiographic findings and heterogeneous lesional tissue. Increasingly, the role of genomic alterations is being recognized for both diagnosis and treatment of ECD. More than half of ECD patients harbor the BRAFV600E mutation. Evaluation for this mutation be can falsely negative on immunohistochemical staining and confirmation with molecular analyses is recommended. We present a case of the 44 year-old male with BRAFV600E-positive ECD treated successfully with steroids followed by single-agent dabrafenib.

Cardiac magnetic resonance imaging (cardiac MRI) is an essential tool in the diagnosis and managing cardiac pathology. This pictorial essay discusses 3 patient case examples used in clinical practice. The cases are representative of very rarely cardiac involvement in Erdheim-Chester disease, where advanced imaging techniques play a crucial role in identifying and evaluating sporadic manifestations in the heart. Cardiac MRI is invaluable in providing detailed structural and functional information. Essential for comprehensive cardiac assessment, it is crucial in guiding effective treatment strategies and improving the patient's outcome with some of the most complex and rare cardiac conditions.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. There are few documented cases in the medical literature. Here, we present an infrequent case of a 53-year-old patient who presented with cutaneous xanthelasma and a gradual decline in general health characterized by asthenia, anorexia, and chronic dyspnea over the last 5 years. Chest, abdominal, and pelvic CT scans revealed distinct findings suggestive of ECD, including peri-renal fat infiltration resulting in the “hairy kidney” sign, hepatosplenomegaly, renal artery ostial stenosis, pneumopericardium thickening, interstitial lung parenchymal involvement, metaphyseal-diaphyseal osteosclerosis affecting long bones, and sinus osteosclerosis. A biopsy confirmed the diagnosis. This case highlights the importance of radiologists being familiar with the characteristic radiologic signs of ECD to avoid unnecessary repeat examinations, delays in diagnosis, or misdiagnosis.

An uncommon benign histiocytic illness, Rosai-Dorfman disease (RDD) mostly affects lymph nodes but can also manifest as extranodal involvement. We describe a case of a female patient, sixty years of age, who had joint discomfort, sleeplessness, weight loss, and headache and eye problems. A heterogeneously hypodense perirectal mass was seen on imaging. Other histiocytic diseases, metastatic cancer, and lymphoma were among the differential diagnosis. Through biopsy and immunohistochemistry staining, which revealed S-100 and CD68 positivity with CD1a negative, a definitive diagnosis of RDD was made. Over a 2-year period following surgical excision, the patient's symptoms significantly improved and there was no sign of recurrence. This example emphasizes the significance of taking RDD into account when making a differential diagnosis for perirectal tumors and the function of imaging in conjunction with histological testing in guiding management.

This case report describes the potential utility of MR spectroscopy and MR perfusion imaging in a patient with central nervous system involvement of Erdheim-Chester disease (ECD). A 57-year-old male presented with a variety of neurological symptoms, and conventional MRI of the brain showed multiple supratentorial and infratentorial findings that generated a wide differential diagnosis. Advanced MRI sequences along with subsequent CT imaging of the abdomen and ultimately a renal biopsy helped narrow the differential and confirm the diagnosis of ECD. Case reports of ECD are sporadic, and the role of advanced neuroimaging in diagnosing this disease has not been fully elucidated.

Background Erdheim-Chester disease (ECD) is a rare histiocytic neoplastic disease, with a wide range of clinical manifestations from mild, localised disease to multi- systemic, life-threatening disease. Materials and Methods This report presents the case of a 64-year-old man who presented with a 2-year history of worsening diplopia, dysarthria, upper and lower limb incoordination, truncal and gait ataxia. Results Subsequent investigations confirmed the diagnosis of ECD. This patient received targeted therapy with BRAF and MEK inhibitors and demonstrated a positive response to treatment with functional gains and reduced disease burden on MR brain imaging. His rehabilitation care and follow up required an interdisciplinary team approach, provided by a rehabilitation physician, physiotherapist, occupational therapist, nutritional therapist, speech therapist, psychologist and social worker. The rehabilitation program consisted of stretching, range of movement exercises, muscle strengthening, balance and flexibility exercises, functional task retraining, equipment provision, fatigue management, nutritional optimisation, targeted communication strategies, psychological support and implementation of services and supports assist his transition towards community reintegration. Conclusion Shared interdisciplinary team and patient goal-setting and timely delivery of cancer rehabilitation interventions were critical in helping maximise this patient’s functional independence, psychosocial outcomes and quality of life.

BRAF V600E mutations are frequently found in histiocytic/dendritic cell neoplasms such as Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH), but few reports have also described BRAF mutations in Rosai-Dorfman disease (RDD), and even these cases may predominantly represent mixed histiocytosis. BRAF mutations have been studied in histiocytic/dendritic cell neoplasms and described to be associated with increased risk of relapse and long-term consequences, but few studies have examined BRAF V600E mutation in RDD, which is recognized as a neoplasm given the high frequency of MAPK pathway alterations. Here, we report a case of BRAF V600E-mutated RDD in a patient who presented with generalized lymphadenopathy. During our evaluation of this patient, we also found expression of PD-L1 in neoplastic histiocytes. During our review period, only few cases of RDD reported to harbor BRAF mutation or were evaluated for the expression of PDL1 by neoplastic cells. Given the potential challenges in distinguishing RDD from other histiocytic/dendritic cell neoplasms, including mixed histiocytosis with similar clinicopathological manifestations, we will discuss the current state of knowledge regarding the frequency and clinical impact of BRAF V600E in RDD, as well as the role of BRAF mutations in RDD pathogenesis. Distinction of BRAF V600E mutated histiocytic/dendritic cell neoplasms requires consideration of distinctive histopathological and immunophenotypic findings in appropriate clinical and radiologic setting. Given the increasing use of BRAF inhibitors as well as checkpoint blockade inhibitors to treat a number of cancers, we will discuss the clinical implications of the presence of BRAF V600E mutation and PD-L1 expression in RDD. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) and Erdheim–Chester disease (ECD) are exceptionally rare disorders characterized by varied clinical presentations, posing several challenges for clinicians. The concomitant occurrence of LCH and ECD is exceedingly rare and has no known etiology. In this report, we present a rare case of mixed histiocytosis (both ECD and LCH) with multisystem involvement. The patient, a 49-year-old female, initially presented with a rash 2 years ago and progressively developed exophthalmos, fatigue, and shortness of breath. She lacked the mutation in codon 600 of exon 15 of B-Raf proto-oncogene (BRAF-V600E) and subsequently underwent treatment with corticosteroids, interferon-alpha, and chemotherapy, all of which proved ineffective. This work highlights the urgent need to improve treatment outcomes for such patients. Therefore, we discuss the latest advancements in understanding treatment strategies for mixed histiocytic syndromes. [ABSTRACT FROM AUTHOR]

PURPOSE: BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective. METHODS: We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations. These alterations were studied through genomic and in silico analyses when applicable, then treated with off-label medications rationally selected on the basis of genomic alterations. RESULTS: Patient 1 had rapidly progressive ECD involving the CNS. A CSF1R in-frame deletion (p.S560_P566del) was identified, and in silico modeling predicted a gain-of-function mutation. This alteration was targeted with pexidartinib, which led to a clinical complete response (CR) within 2 months, and a partial response (PR) on imaging after 3 months. After 15 months, the disease became resistant to pexidartinib and transformed to histiocytic sarcoma. Patient 2 has skin-only involvement of a xanthogranuloma disorder. A KIF5B-FGFR1 fusion was identified on RNA sequencing and targeted with pemigatinib. At 24 months of follow-up, she remains in a clinical PR. Patient 3 has ECD involving the bone marrow, gastrointestinal tract, and subcutaneous tissues. A MEF2C-FLT3 fusion was identified and targeted with sorafenib. He achieved a clinical CR and radiographic PR within 3 months, which has continued for 30 months. CONCLUSION: We report three patients with histiocytic disorders harboring novel alterations who had sustained responses to off-label kinase inhibitors specific to their histiocytic disorder. Pathogenic variants outside of the MAPK pathway, including variants of unknown significant, may be targeted with readily available small molecules. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Crystal‐storing histiocytosis (CSH) is a rare form of histiocytosis with intralysosomal accumulations of immunoglobulins or paraproteins that aggregate as crystals. Central nervous system (CNS) involvement of CSH is uncommon but should be considered in cases of persistent parenchymal enhancement on neuroimaging.We describe one local case of CNS CSH and 10 additional cases identified by literature review.Among 11 CSH patients, lesions involved either the dura (2/11) or brain parenchyma (9/11). Two cases had leptomeningeal enhancement. One case had spinal cord involvement. Two cases were associated with marginal zone lymphoma; one case was associated with an immunoglobulin A‐plasma cell dyscrasia. Eight of 11 cases had outcome data available: 7/8 cases had clinical and/or radiological improvement and 1/8 had radiological stability.Central nervous system involvement of CSH is rare. Potential cases should be comprehensively evaluated for lymphoma or myeloma with positron emission tomography/computed tomography (CT) of the body or alternatively, CT of the chest, abdomen, pelvis and nuclear bone scan, bone marrow biopsy, serum protein electrophoresis, and cerebrospinal fluid protein electrophoresis. Treatment is targeted toward the underlying malignancy. [ABSTRACT FROM AUTHOR]

Tenosynovial giant cell tumor (TGCT) is a rare type of tumor that originates from the synovium of joints and tendon sheaths. It is characterized by recurring genetic abnormalities, often involving the CSF1 gene. Common symptoms include pain and swelling, which are not specific to TGCT, so MRI and a pathological biopsy are needed for an accurate diagnosis. We report the case of a 45-year-old man who experienced painful swelling in his right hip for six months. Initially, this was diagnosed as Erdheim-Chester disease. However, whole exome sequencing (WES) and RNA-Sequencing revealed a CSF1::GAPDHP64 fusion, leading to a revised diagnosis of TGCT. The patient was treated with pegylated interferon and imatinib, which resulted in stable disease after three months. Single-cell transcriptome analysis identified seven distinct cell clusters, revealing that neoplastic cells expressing CSF1 attract macrophages. Analysis of ligand-receptor interactions showed significant communication between neoplastic cells and macrophages mediated by CSF1 and CSF1R. Our findings emphasize the importance of comprehensive molecular analysis in diagnosing and treating rare malignancies like TGCT. [ABSTRACT FROM AUTHOR]

This document provides abstracts of clinical case presentations from the 2024 Vascular Scientific Sessions of the Society for Vascular Medicine. The cases cover a range of vascular conditions and highlight the challenges in diagnosing and managing these conditions. Topics include pulmonary embolism, Erdheim-Chester disease, polycythemia vera, cyanoacrylate closure, antiphospholipid syndrome, heavy metal toxicity, aortic aneurysms, COVID-19 multisystem inflammatory syndrome, large vessel vasculitis, arterial dissections, acute limb ischemia, ruptured abdominal aortic aneurysm, deep venous thrombosis, thoracic outlet syndrome, carotidynia, adrenal leiomyosarcoma, aortic dissection, transgender health, giant cell arteritis, cancer-related venous thrombosis, and vasopressor-induced peripheral ischemia. The cases emphasize the need for prompt diagnosis, appropriate management, and consideration of alternative treatments when necessary. [Extracted from the article]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by xanthomatous infiltration of affected organs. We present a case of a 62-year-old man with ECD initially presenting with constrictive pericarditis. Comprehensive imaging revealed systemic involvement, including the skeleton, orbit, pituitary, lung, kidney, and retroperitoneum, despite the absence of related symptoms. The diagnosis of ECD was eventually confirmed through histopathological evidence from a CT-guided biopsy. The patient responded well to interferon-α2b treatment, with gradual symptom amelioration and improvement in imaging and laboratory findings over a 5-month follow-up period. This case highlights the importance of considering ECD in the differential diagnosis of constrictive pericarditis and the utility of multimodal imaging for accurate diagnosis and management of this rare disease. The patient's positive response to treatment also highlights the potential for effective management of ECD, particularly with early diagnosis and intervention.

Histiocytoses are rare diseases characterised by infiltration of affected organs by myeloid cells with a monocyte or dendritic cell phenotype. Symptoms can range from self-resolving localised forms to multisystemic lesions requiring specific treatment. To demonstrate extremely rare cases of CD68-negative cardiac histiocytosis with expression of SARS-CoV-2 antigen in infiltrate cells. We demonstrated a case of Erdheim–Chester disease in a 67-year-old man with pericardial involvement and positive dynamics with vemurafenib treatment, an autopsy case of xanthogranulomatous myopericarditis in a 63-year-old man, surgical material of xanthogranulomatous constrictive pericarditis in a 57-year-old man, and an autopsy case of xanthogranulomatosis in a 1-month-old girl. In all cases, xanthogranuloma cells expressed CD163, many of them spike protein SARS-CoV-2, while CD68 expression was detected only in single cells. In this article, we demonstrated four cases of extremely rare CD68-negative cardiac xanthogranulomatosis in three adults and one child with expression of the spike protein SARS-CoV-2 in M2 macrophages. This potential indirect association between COVID-19 and the development of histiocytosis in these patients warrants further investigation. To substantiate this hypothesis, more extensive research is needed. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a newborn with high-risk Langerhans cell histiocytosis (LCH) treated with a combination of Vemurafenib, cytarabine, and cladribine. The patient showed clinical improvement and durable remission, but the BRAFV600E-positive clone persisted despite treatment. The study highlights the challenges in eradicating the mutant clone in LCH patients, emphasizing the importance of long-term molecular monitoring to assess treatment effectiveness. The authors suggest that while clinical efficacy is crucial, achieving a definitive cure may require eradicating the mutant clone residing in the bone marrow. [Extracted from the article]

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by systemic fibro-inflammatory infiltrates and an unfavorable prognosis. The disease has gained increasing interest due to a rise in cases, and consensus guidelines for diagnosis and management have been developed. ECD is generally diagnosed in middle-aged adults, with a higher incidence in males. Diagnostic challenges arise due to the variety of clinical manifestations and the need for differential diagnosis with other conditions such as idiopathic retroperitoneal fibrosis and chronic recurrent multifocal osteomyelitis. Thorough assessment and biopsy of fibrous tissue are recommended for accurate diagnosis and targeted genetic therapies. [Extracted from the article]

Key Clinical Message: Diagnosis of Erdheim–Chester disease (ECD) requires the clinician to be familiar with its various manifestations, classic radiologic and histologic features. This case highlights the significance of considering ECD in any patient presenting with bone pain and symmetric osteosclerosis of long bones of extremities to allow for early diagnosis and treatment. Erdheim–Chester disease (ECD) is a rare non‐Langerhans histiocytic disorder with diverse clinical manifestations, ranging from indolent, localized presentation to life‐threatening, multi‐systemic disease. Delayed or erroneous diagnosis is common. The presence of classic radiographic finding along with foamy histiocytes that is positive for CD68 but negative for CD1a on histologic examination establishes the diagnosis. We report a second case of ECD from Ethiopia. A 50‐year‐old Ethiopian man presented with a 13‐year history of bilateral lower leg bone pain, cold intolerance, somnolence, constipation, impotence, decreased libido, and secondary infertility. The diagnosis was suspected when skeletal X‐ray revealed bilateral symmetric sclerosis of metadiaphysis of femur, tibia, and humerus. The demonstration of foamy histiocytes that were positive for CD68 but negative for CD1a on histologic examination with immunohistochemical staining confirmed the diagnosis. Evaluation for the extent of the disease revealed coated aorta sign, hairy kidney sign, and cystic lesion with ground glass opacity of lung, primary hypothyroidism, and hypergonadotropic hypogonadism. ECD is rare histiocytic neoplasm with wide range of clinical features which often delay the diagnosis. Clinician should be mindful of the various presentations and the classic radiographic and histologic features of ECD. This case highlights the significance of entertaining ECD in any patient presenting with lower leg bone pain and symmetric osteosclerosis of long bones of lower extremities to allow for early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Pulmonary Langerhans cell histiocytosis (PLCH) is a subtype of Langerhans cell histiocytosis, a rare neoplastic disease characterized by lung involvement. Here, we present a case involving a patient with multiple cavitary nodules who was diagnosed with PLCH during surveillance after lung cancer surgery. A 74‐year‐old woman underwent right upper lobe resection surgery for right upper lobe lung adenocarcinoma, pStage IIA, 5 years ago. The patient underwent surveillance without adjuvant chemotherapy. During the fifth year of follow‐up, multiple nodules with cavitation were observed on computed tomography in both lung fields. Chemotherapy was considered to address the suspected recurrence of lung cancer; however, video‐assisted thoracoscopic surgery was performed due to the need for biomarker testing. Pathological examination led to the diagnosis of PLCH. This case emphasizes the importance of a proactive histological diagnosis to determine the appropriate treatment strategy, even in situations where lung cancer recurrence is clinically suspected. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses Poland's first case of Erdheim-Chester Disease (ECD) with cerebellar manifestations, a rare inflammatory disorder with only about 1,500 documented cases worldwide. The case study highlights the diagnostic and therapeutic challenges faced by neurological specialists in treating ECD. The patient, a 39-year-old male, presented with speech difficulties, gait problems, weight loss, and other neurological symptoms, leading to the diagnosis of ECD confirmed through genetic testing. Treatment with vemurafenib was initiated, and the patient remained stable for two years under continuous medical follow-up. [Extracted from the article]

Purpose: This study investigates the accuracy of either computerized tomography (CT) or magnetic resonance imaging (MRI) for the evaluation of various orbital diseases. Methods: We collected 126 CT scans and 65 MRI scans from 144 subjects and asked two radiologists to interpret the images without clinical information. Images included 14 with a clinical diagnosis of orbital infection, 144 with orbital inflammation, and 33 with orbital neoplasm. The inflammatory diseases included thyroid eye disease (TED, n = 69), non-specific orbital inflammation (NSOI, n = 44), IgG4-related disease (IgG4-RD, n = 15), sarcoidosis (Sarcoid, n = 9), granulomatosis with polyangiitis (GPA, n = 5), and Erdheim-Chester disease (ECD, n = 2). Results: The balanced accuracy (BA) for the two radiologists ranged from 0.87 to 0.90 for cellulitis, 0.81 to 0.86 for inflammation, and 0.82 to 0.85 for neoplasm. Radiologists were excellent at recognizing GPA (BA = 0.98 to 0.99) and very good for TED (BA = 0.80 to 0.86). They also did well identifying IgG4-RD (BA = 0.75 to 0.77), but slightly less well for NSOI (BA = 0.69 to 0.75) and poorly for Sarcoid (BA = 0.48 to 0.50). Conclusions: CT or MRI scanning contributes to the evaluation of patients with orbital disease, but accuracy does varies based depending on the diagnosis. We could not evaluate issues such as determination of disease activity, variability based on the unit used for imaging or the skills beyond those of our two specialized neuroradiologists. Future studies should directly compare the two imaging modalities and assess the utility of imaging to determine disease activity. [ABSTRACT FROM AUTHOR]

Aims: Early detection and treatment of neurodegenerative Langerhans cell histiocytosis (ND-LCH) have been suggested to prevent neurodegenerative progression. The aim of the study is to validate a standardized multidisciplinary diagnostic work-up to monitor the intravenous immunoglobulins (IVIG) treatment response and the natural course of the disease in untreated patients. Methods: Patients with abnormal somatosensory evoked potentials (SEPs) received monthly 0.5 g/kg IVIG. The diagnostic protocol included structural 3T MRI, neurological examination, brainstem auditory evoked potentials (BAEPs) and SEPs. Results: Twenty-two patients were followed for 5.2 years (median) from the first MRI evidence of ND-LCH. Eleven patients received IVIG for 1.7 years (median). At treatment start neurological examination was abnormal in 10 patients, of whom two had severe clinical impairment and four had abnormal BAEPs. At last followup, 1/11 remained stable and 7/11 improved, while worsening of neurological or neurophysiological findings, or both, occurred in 3/11. Risk factors for worsening were a severe clinical or MRI ND-LCH at treatment initiation and prolonged exposure to LCH. Of the 11 untreated patients, none improved and three worsened. Conclusions: Using a standardized diagnostic protocol, we demonstrated that IVIG treatment can lead to clinical stabilization or improvement in all paucisymptomatic patients with an MRI grading of less than 4. [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring. [ABSTRACT FROM AUTHOR]

This article discusses a case of normolipemic xanthoma associated with folliculotropic mycosis fungoides (fMF), a variant of mycosis fungoides. The patient, a 60-year-old Japanese man, presented with yellowish masses and patchy alopecia on the scalp, as well as follicular papules on the trunk and extremities. Trichoscopy and histological analysis revealed mucin deposition, lymphocyte and eosinophil infiltrations, and dense infiltration of histiocytes mixed with eosinophils and lymphocytes. The article suggests that the tumour microenvironment triggers histiocyte infiltration, which may lead to xanthoma formation. The case highlights the challenges in diagnosing fMF due to excessive granulomatous/xanthomatous components and emphasizes the importance of a comprehensive assessment for a definitive diagnosis. [Extracted from the article]

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a‐positive/Langerin (CD207)‐positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life‐threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard‐of‐care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long‐term morbidity, including the risk of LCH‐associated neurodegeneration. Historically, the nature of LCH—whether a reactive condition versus a neoplastic/malignant condition—was uncertain. Over the past 15 years, seminal discoveries have broadly defined LCH pathogenesis; specifically, activating mitogen‐activated protein kinase pathway mutations (most frequently, BRAFV600E) in myeloid precursors drive lesion formation. LCH therefore is a clonal neoplastic disorder, although secondary inflammatory features contribute to the disease. These paradigm‐changing insights offer a promise of rational cures for patients based on individual mutations, clonal reservoirs, and extent of disease. However, the pace of clinical trial development behind lags the kinetics of translational discovery. In this review, the authors discuss the current understanding of LCH biology, clinical characteristics, therapeutic strategies, and opportunities to improve outcomes for every patient through coordinated agent prioritization and clinical trial efforts. Langerhans cell histiocytosis is an inflammatory myeloid neoplastic disorder driven by activating somatic mutations in mitogen‐activated protein kinase pathway genes. Rapid advances in mechanistic understanding of Langerhans cell histiocytosis now offer opportunities to improve outcomes for patients. [ABSTRACT FROM AUTHOR]

This case report highlights a unique presentation of Erdheim-Chester Disease (ECD) with bilateral scleral lesions, choroidal infiltration, and extensive sinus involvement. It is the first case report where the diagnosis was confirmed through a scleral biopsy after an initial presentation of a unilateral nodular scleritis. There was a gradual disease progression and ocular examination later revealed bilateral subconjunctival hyperemic lesions and mild exophthalmos, ophthalmoplegia, and extensive choroidal infiltration. Infiltration of the frontal and maxillary sinus was present and extended into the nasal cavity and both orbits. The diagnostic work-up is described in detail. Current treatment options are analyzed. It is emphasized that the ophthalmologist can play a crucial role in the diagnosis of ECD, given the substantial prevalence of orbital and ocular symptoms. The overall prognosis for ECD remains unfavorable, particularly in cases with orbital involvement. This case underscores the complexity and importance of a multidisciplinary approach in managing ECD. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a common chronic, recurrent, and non-infectious inflammatory skin disease. Dupilumab is a human monoclonal antibody with clinical efficacy in severe AD and has a good safety profile. Case Presentation: We hereby describe a previously unreported case of multisystem Langerhans cell histiocytosis (MS-LCH) that is associated with a history of AD treatment using dupilumab. Conclusion: A single case of MS-LCH with a history of dupilumab treatment for AD was described for the first time. This case highlights that given its susceptibility to skin involvement, LCH needs to be considered as a differential diagnosis for skin lesions that are not improved by established therapies. [ABSTRACT FROM AUTHOR]

This article discusses the recurrent chromosomal translocation ETV6:SYK fusion in myeloid malignancies. The fusion of the ETV6 oncogene with tyrosine kinase genes such as SYK has been identified in various hematological malignancies and solid tumors. The World Health Organization (WHO) and International Consensus Classification (ICC) recognize this fusion as a category of myeloid neoplasms. Targeted therapies using tyrosine kinase inhibitors (TKIs) have shown promise in treating malignancies with ETV6:SYK fusion. However, the fusion is not currently listed in the WHO or ICC classifications, and further research is needed for its inclusion. The article also presents a case study of a patient with ETV6:SYK fusion and discusses the potential use of SYK inhibitors and downstream pathway targeting in treatment. [Extracted from the article]