Histological evidence of MAPK pathway activation across subtypes of adult orbital xanthogranulomatous disease irrespective of the detection of oncogenic mutations.

Adult orbital xanthogranulomatous disease (AOXGD) is a spectrum of histiocytoses with four subtypes. Mitogen-activated protein kinase (MAPK) pathway mutations have been detected in various histiocytic neoplasms, little is known about this in AOXGD. Targeted regions of cancer- and histiocytosis-related genes were analyzed and immunohistochemical staining of phosphorylated ERK (pERK), cyclin D1 and PU.1 was performed in 28 AOXGD and 10 control xanthelasma biopsies to assess MAPK pathway activation. Mutations were detected in 7/28 (25%) patients. Positive staining for pERK and/or cyclin D1 was found across all subtypes in 17/27 (63%) patients of whom 12/17 (71%) did not harbour a mutation. Xanthelasma tissue stained negative for pERK and cyclin D1. Relapse occurred in 5/7 (71%) patients with a MAPK pathway mutation compared to 8/21 (38%) patients in whom no mutation could be detected. Molecular analysis and evaluation for systemic disease is warranted to identify patients at risk of recurrent xanthomatous disease.

Co-occurrence of Erdheim-Chester disease and clonally evolving acute myeloid leukemia with FLT3-ITD and PTPN11 mutations.

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.

Cardiovascular manifestations of Erdheim-Chester disease: A narrative review with two cases.

Erdheim-Chester disease (ECD) is a rare 'L' (Langerhans) group histiocytic neoplasm that affects a multitude of organ systems, causing osteosclerotic bone lesions, periaortic encasement ('coated' aorta), retroperitoneal fibrosis involving kidneys and ureters ('hairy kidney'), and infiltration of the central nervous system. Cardiovascular involvement can occur in up to 70% of patients and is usually found during computed tomography/magnetic resonance imaging evaluation. When present, cardiovascular symptoms can have wide variability in presentation from asymptomatic to pericarditis, fatal cardiac tamponade, myocardial infarction, conduction abnormalities, heart failure, renal artery stenosis, and claudication. Cardiac involvement found on imaging includes right atrial pseudotumor, right atrioventricular groove infiltration, and pericardial effusions. ECD can involve the large- and medium-sized arteries, often seen as periarterial thickening (commonly coating the aorta) with stenosis/occlusion. Although more cardiovascular ECD cases have begun to be published in the literature, more data are needed on the outcomes of these patients, as well as how cardiovascular manifestations respond to treatment of ECD.

Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.

Erdheim-Chester disease and nuclear medicine imaging. A case report and brief review.

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.

Prevalence, patterns and outcomes of cardiac involvement in Erdheim-Chester disease.

AIMS: Cardiac involvement of Erdheim-Chester disease (ECD), a rare L group histiocytosis, has been reported to be associated with poor outcomes, but systematic studies are lacking. The present study aimed to investigate the prevalence, clinical features, imaging features, and prognosis of cardiac involvement in ECD in a large series. METHODS AND RESULTS: All patients with ECD who underwent cardiac magnetic resonance (CMR) imaging between 2003 and 2019 at a French tertiary center were retrospectively included. Primary outcome was all-cause mortality. Secondary outcomes were pericarditis, cardiac tamponade, conduction disorders, device implantation and coronary artery disease (CAD). A total of 200 patients were included [63 (54-71) years, 30% female, 58% BRAFV600E mutated]. Median follow-up was 5.5 years (3.3-9 years). On CMR, right atrioventricular sulcus infiltration was observed in 37% of patients, and pericardial effusion was seen in 24% of patients. In total, 8 patients (4%) had pericarditis (7 acute, 1 constrictive), 10 patients (5%) had cardiac tamponade, 5 patients (2.5%) had ECD-related high-degree conduction disorders, and 45 patients (23%) had CAD. Overall, cardiac involvement was present in 96 patients (48%) and was associated with BRAFV600E mutation [Odds ratio (OR) = 7.4, 95% confidence interval (CI) (3.5-16.8), P < 0.001] and ECD-related clinical events [OR = 5, 95%CI (1.5-21.2), P = 0.004] but not with lower survival in multivariate analysis [adjusted hazard ratio (HR) = 1.4, 95% CI (0.8-2.5), P = 0.2]. CONCLUSION: Cardiac involvement is present in nearly half of ECD patients and is associated with BRAFV600E mutation and complications (pericarditis, cardiac tamponade, and conduction disorders) but not with lower survival.

Unusual orbital, scleral and choroidal findings in Erdheim-Chester disease: a case report.

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.

Erdheim-Chester disease: misdiagnosed as multiple sclerosis.

Erdheim-Chester disease is a rare histiocytic neoplasm with a wide range of clinical manifestations. Due to its rarity and protean characteristics, this condition often presents a diagnostic challenge. A Caucasian woman in her late 60s presented with unsteadiness, dysphagia and dysarthria. She was initially diagnosed with secondary progressive multiple sclerosis but deteriorated over 2 years with a potential lack of therapeutic response. Subsequent investigations resulted in the diagnosis of Erdheim-Chester disease. She received targeted therapy with BRAF and MAPK-pathway inhibitors. Her initial response to treatment has been positive with functional gains and reduced disease burden on MR brain imaging, and with no significant adverse effects.

Orbital histiocytosis; From A to Z.

PURPOSE: Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. METHOD: This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. RESULTS: 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. CONCLUSION: Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.

Clinical phenotypes and long-term outcome of kidney involvement in Erdheim-Chester histiocytosis.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that frequently infiltrates the peri-kidney space ("hairy kidney" appearance), kidney pelvis and proximal ureters, leading to obstructive uropathy. Here, we analyzed the clinical characteristics, imaging findings and long-term kidney outcome of a large multicenter cohort comprising 195 consecutive patients with ECD. Retroperitoneal peri-kidney or peri-ureteral involvement was detected at diagnosis in 147 patients. Of them, 70 had hydronephrosis (bilateral in 47), and 16 with kidney atrophy (unilateral in 14). Kidney vascular peduncle infiltration was found in 60 patients, and kidney artery stenosis in 31. The estimated glomerular filtration rate (eGFR) at diagnosis was significantly lower in patients with than in those without peri-kidney involvement (median 74 vs. 98 mL/min/1.73 m2). Ureteral stenting often failed to achieve kidney function recovery. A total of 181 patients received medical therapies: first-line treatments included interferon-α (61%), BRAF-inhibitors (17%), mTOR-inhibitors (7%), or other drugs (15%). These therapies were efficacious for ECD but rarely induced kidney function improvement (one-year eGFR increase over 25% in under 10% of patients). After a median of 43 months, 19% of patients died and 5% developed kidney failure. Among patients with peri-kidney involvement, 44% developed chronic kidney disease (CKD) 3-5 at five years vs. 5% of those without. Unadjusted predictors of advanced CKD and kidney failure/death were age over 50 years, hypertension, BRAFV600E mutation, and baseline eGFR. At multivariable analysis, cardiovascular comorbidities were associated with advanced CKD, and age over 50 years with kidney failure/death. Thus, kidney involvement is common in ECD and can lead to CKD or kidney failure despite effective medical therapies or urological procedures.

The clinical spectrum and prognostic factors of Erdheim-Chester disease and mixed Langerhans cell histiocytosis and Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare and probably fatal multisystemic non-Langerhans cell histiocytosis (LCH). To comprehensively investigate the clinical features, genomic analysis, treatments, and prognostic factors of ECD, we retrospectively analyzed the clinical data of 75 ECD patients and 10 mixed LCH and ECD patients in our center. The median age at diagnosis was 46 years (range, 5-70). ECD patients were older at diagnosis (p = 0.006) and had more cardiac involvement (p = 0.011) as well as vascular (p = 0.031) involvement compared to mixed LCH and ECD patients. 64.8% of ECD patients and 87.5% of mixed LCH and ECD patients carried BRAFV600E mutation. The BRAFV600E mutation correlated with a greater number of affected organs (p = 0.030) and was associated with lung involvement (p = 0.033) as well as pleural involvement (p = 0.002). The median follow-up time was 38 months (range, 1-174). The estimated 5-year progression-free survival (PFS) and overall survival (OS) were 48.9% and 84.7%, respectively. In a multivariate analysis, right atrial pseudotumor (p = 0.013) and pancreatic involvement (p = 0.005) predicted worse OS, while pleural (p = 0.042) and central nervous system (CNS) involvement (p = 0.043) predicted worse PFS. Our study described the clinical spectrum of ECD and mixed LCH and ECD, while also revealed the prognostic value of right atrial pseudotumor and pancreatic, pleural, and CNS involvement for worse survival.

Comparison of neuroimaging features of histiocytic neoplasms with central nervous system involvement: a retrospective study of 121 adult patients.

OBJECTIVES: To compare neuroimaging characteristics of three types of histiocytoses, namely Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD), with central nervous system (CNS) involvement. METHODS: A total of 121 adult patients with histiocytoses (77 LCH, 37 ECD, and 7 RDD) and CNS involvement were retrospectively included. Histiocytoses were diagnosed based on histopathological findings combined with suggestive clinical and imaging features. Brain and dedicated pituitary MRIs were systematically analyzed for tumorous, vascular, degenerative lesions, sinus, and orbital involvement and for hypothalamic pituitary axis involvement. RESULTS: Endocrine disorders, including diabetes insipidus and central hypogonadism, were more common in LCH patients than in ECD and RDD patients (p < 0.001). In LCH, tumorous lesions were mostly solitary (85.7%), located in the hypothalamic pituitary region (92.9%), and without peritumoral edema (92.9%), while in ECD and RDD, tumorous lesions were often multiple (ECD: 81.3%, RDD: 85.7%), their distribution was more widespread with meninges mostly involved (ECD: 75%, RDD: 71.4%), and they most likely presented with peritumoral edema (ECD: 50%, RDD: 57.1%; all p ≤ 0.020). Vascular involvement was an exclusive imaging characteristic of ECD (17.2%), which was not observed in LCH or RDD; this was also associated with a higher risk of death (p = 0.013, hazard ratio = 11.09). CONCLUSION: The typical characteristic of adult CNS-LCH was endocrine disorders with radiological findings limited to the hypothalamic pituitary axis. The pattern of multiple tumorous lesions with predominant involvement of meninges was the main manifestation of CNS-ECD and CNS-RDD, while vascular involvement was pathognomonic for ECD and associated with poor prognosis. CLINICAL RELEVANCE STATEMENT: Involvement of the hypothalamic-pituitary axis is the typical imaging characteristic of Langerhans cell histiocytosis. Multiple tumorous lesions, predominantly involving but not limited to meninges, occur in most Erdheim-Chester disease and Rosai-Dorfman disease patients. Vascular involvement occurs only in Erdheim-Chester disease patients. KEY POINTS: • The different distribution patterns of brain tumorous lesions can help differentiate among LCH, ECD, and RDD. • Vascular involvement was an exclusive imaging finding of ECD and was associated with high mortality. • Some cases with atypical imaging manifestations were reported to further expand the knowledge on these diseases.

Neurological Manifestations of Histiocytic Disorders.

PURPOSE OF REVIEW: Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. RECENT FINDINGS: Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.

Erdheim-Chester Disease with BRAF V600E Mutation and a Concomitant Myeloid Malignancy Sharing NRAS and IDH2 Mutations.

Erdheim-Chester disease (ECD) is a rare clonal histiocytic process that is characterized by a foamy (xanthomatous) proliferation often associated with Touton giant cells. The diagnosis is often challenging and not exclusively a histologic diagnosis, as it requires correlation with unique clinical, radiographic, and recently described molecular findings. Activating mutations involving the MAPK pathway including BRAF, ARAF, N/KRAS, and MEK are recurrent in the disease. However, it is increasingly being described that mutations associated with clonal hematopoiesis are also found in bone marrow specimens of patients with ECD, as well as higher frequency of overt concomitant myeloid malignancy including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes, and mixed myeloproliferative neoplasms/myelodysplastic syndromes. Herein, we report a unique case of a patient presenting with BRAFV600E-positive ECD with peripheral blood findings consistent with a concurrent myeloid malignancy featuring co-occurrence of NRAS and IDH2 mutations.

Erdheim-Chester disease: diffusion-weighted imaging and dynamic contrast-enhanced MRI provide useful information.

This is, to our knowledge, the first case report with in-depth analysis of bone marrow and bone lesions with diffusion-weighted imaging and dynamic contrast-enhanced MRI in Erdheim-Chester disease to date. We present a case of a 70-year-old woman who was referred for an X-ray of the pelvis, right femur and right knee after complaints of migratory arthralgia in hip and knee five months after an initial hip and knee trauma. Bone lesions on X-ray were identified. This case report highlights the strength and complementary use of modern multimodality multiparametric imaging techniques in the clinical radiological manifestations of Erdheim-Chester disease, in the differential diagnosis and in treatment response assessment, which is classically performed using 18FDG PET-CT. Erdheim-Chester disease is a rare form of non-Langerhans' cell histiocytosis, mainly affecting individuals in their fifth-seventh decade of life and without sex predominance. Apart from the typical bilateral symmetric lesions in long bone diaphyseal and metaphyseal regions and classically sparing the epiphyses, this multisystemic disease causes significant morbidity by infiltrating critical organs (the central nervous system, cardiovascular system, retroperitoneum, lungs and skin). With non-traumatic bone pain being the most common complaint, Erdheim-Chester disease is diagnosed most often in an incidental setting on imaging. The imaging workup classically consists of a multimodality approach using conventional radiography, CT, MRI, bone scintigraphy and 18FDG PET-CT. This case report extends this evaluation with diffusion-weighted imaging and dynamic contrast-enhanced imaging techniques.

Cardiovascular involvement in Erdheim-Chester diseases is associated with myocardial fibrosis and atrial dysfunction.

PURPOSE: Erdheim-Chester disease (ECD) is a rare multisystem histiocytosis, whose cardiovascular involvement has not been systematically characterized so far. We aimed to systematically (qualitatively and quantitatively) describe the features of cardiovascular involvement in a large cohort of ECD patients and to evaluate its impact on myocardial fibrosis extension and cardiac function. MATERIAL AND METHODS: Among 54 patients with biopsy-proven ECD, 29 patients (59 ± 12 years, 79% males) underwent 1.5-T CMR using a standardized protocol for qualitative and quantitative assessment of disease localization, evaluation of atrial and ventricular function, and assessment of non-dense and dense myocardial fibrosis. RESULTS: The right atrioventricular (AV) groove was the most commonly affected cardiac site (76%) followed by the right atrial walls (63%), thoracic aorta (59%), and superior vena cava (38%). Right AV groove involvement, encasing the right ventricular artery, was associated with non-dense myocardial fibrosis in the infero-septal (20/26 patients) and the inferior (14/26 patients) mid-basal left ventricular (LV) wall. In two patients with right AV groove localization, LGE revealed myocardial infarction in the same myocardial segments. Three out of five patients with left AV groove involvement had non-dense LGE on the lateral LV mid-basal wall. Bulky right atrial pseudomass was associated with atrial dysfunction and superior and inferior vena cava stenosis. CONCLUSIONS: In ECD patients, AV groove localization is associated with LV wall fibrosis in the downstream coronary territories, suggesting hemodynamic alterations due to coronary encasement. Conversely, atrial pseudomass ECD localizations impact on atrial contractility causing atrial dysfunction and are associated with atrio-caval junction stenosis.

Erdheim-Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib.

Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging. However, recent breakthroughs in our understanding, particularly the discovery of somatic mutations in the RAS-MAPK pathway, have opened new opportunities for targeted therapy in a significant subset of patients with ECD and other histiocytoses. In this report, we present the case of a patient with ECD harboring a previously unidentified microduplication in the NRAS gene in a small fraction of skin cells. This discovery played a pivotal role in tailoring an effective therapeutic approach involving kinase inhibitors downstream of NRAS. This case underscores the crucial role of deep sequencing of tissue samples in ECD, enabling the delivery of personalized targeted therapy to patients.

Erdheim-Chester disease and vemurafenib: a review of ophthalmic presentations and clinical outcomes.

PURPOSE: To provide a comprehensive review of ocular and orbital manifestations of Erdheim-Chester Disease (ECD) and compare clinical outcomes with vemurafenib (INN) to historical treatments (HT). Primary outcomes are ophthalmic findings on presentation, changes in visual acuity, and mortality rate. Secondary outcomes include the progression of ocular findings, systemic involvements, and treatment modalities. METHODS: All published literature from January 1983 to March 2021 was searched for ophthalmic manifestations of ECD. Clinical outcomes following HT were collected and compared with INN. RESULTS: Forty-seven patients with ECD and ophthalmic presentations were identified. The mean age was 49.6 years (SD = 15.0). Proptosis (65.6%) and extraocular muscle restrictions (42.5%) were the most common presenting signs. Of 41 (87.2%) patients with orbital masses on radiologic examination, 90.2% were bilateral, and 53.7% were located in the intraconal space. Ophthalmic examination was significant for xanthelasma (27.2%), optic disc edema (34.0%), and subretinal changes (21.3%). Common treatments were systemic steroids (76.6%), interferon-α (17.0%), and cyclophosphamide (14.9%). INN was less commonly used (12.8%). The mean change in logMAR visual acuity declined with HT (29.9%) but improved with INN (79.1%) (p > 0.05). The proportion of eyes with complete vision loss increased after HT (p < 0.05). The overall mortality rate was 27.7% and notably higher in the HT group (29.3%) when compared to the INN group (16.7%) (p > 0.05). CONCLUSION: ECD presents with many ophthalmic manifestations. Although the intraocular treatments remain controversial, INN should be highly considered in treating orbital ECD patients with BRAF-V600E mutations to prevent and reverse vision loss.

An Unusual Case of Erdheim Chester Disease (ECD) with Knee Pain: A Case Report.

Background: Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown etiology that occurs in multiple organs. The clinical characteristics of ECD are unknown, making it difficult to diagnose. Case presentation: A 61-year-old woman presented with left knee pain and contracture. She had recent medical problems such as recurrent urinary tract infection, pericardial effusion, and pleural effusion. Simple radiography and magnetic resonance imaging of the knee revealed an osteosclerotic lesion. Under suspicion of malignancy, other radiologic modalities were performed, but there were no significant results showing malignancy. A bone biopsy of the knee lesion led to a final diagnosis of ECD. The patient was treated with systemic steroids and was ultimately tried on PEG-interferon. Conclusion: This report describes an unusual presentation of ECD involving the skeletal system and multiple extraskeletal organs. Owing to its non-specific nature, ECD was notably difficult to diagnose. Therefore, if a patient has knee pain and other multiorgan presentations without malignancy, clinicians should suspect ECD.

Impact of a Multidisciplinary Tumor Board on the Care of Patients with Histiocytic Disorders: The Histiocytosis Working Group experience.

INTRODUCTION: Histiocytic disorders pose significant diagnostic and management challenges for the clinicians due to diverse clinical manifestations and often non-specific histopathologic findings. Herein, we report the tumor board experience from the first-of-its-kind Histiocytosis Working Group (HWG). MATERIALS AND METHODS: The HWG was established in June 2017 and consists of experts from 10 subspecialties that discuss cases in a multidisciplinary format. We present the outcome of tumor board case discussions during the first 2 years since its inception (June 2017-June 2019). RESULTS: Forty cases with a suspected histiocytic disorder were reviewed at HWG during this time period. Average number of subspecialties involved in HWG case discussion was 5 (range, 2-9). Histiocytosis Working Group tumor board recommendations led to significant changes in the care of 24 (60%) patients. These included change in diagnosis (n = 11, 27%) and change in treatment (n = 13, 33%). CONCLUSION: Our report highlights the feasibility of a multidisciplinary tumor board and its impact on outcomes of patients with histiocytic disorders.