Case Of Erdheim-Chester Disease Research Articles

Intracranial mass lesions and skin discoloration in the armpits as unusual clues to Erdheim-Chester disease: a case report

BackgroundErdheim–Chester disease (ECD) is a non-Langerhans histiocytosis that results in multi-organ disease involving the skin, bones, lungs and kidneys. Central nervous system (CNS) involvement occurs in about 50 % of patients, and diabetes insipidus, visual disturbances, and cerebellar ataxia are the most frequent neurological signs. We report a case of Erdheim-Chester disease with central nervous system involvement in the form of enhancing intracranial mass lesions with massive edema.Case presentationThe patient presented with vertigo, ataxia, encephalopathy and pyramidal signs. Diagnosis was suggested by xanthomatous skin lesions and a biopsy was compatible with Erdheim-Chester disease demonstrating xanthogranulomas CD68 positive (clone KP1) and CD1a and S100 negative. Testing for BRAF mutation was negative, which precluded treatment with Vemurafenib. Treatment with steroids and interferon resulted in improvement of neurological signs and regression of edema on MRI.ConclusionsThe diagnosis of Erdheim-Chester disease should be considered in intracranial mass lesions. Xanthomatous skin lesions are a clue to the diagnosis.

15120 Erdheim-Chester disease: Case report with multisystem manifestations

A 61-year-old man presented with a 3-year history of extensive yellow plaques on both eyelids. The patient also reported retro-orbital headache, lower limb pain, polydipsia-polyuria and progressive fatigue, since last year. Reflectance confocal microscopy showed clusters of multinucleated roundish structures, along with discoid-shaped structures, at superficial dermis. Histopathology examination proved them to be Touton cells and foamy histiocytes respectively. Immunohistochemically, foamy histiocytes were positive for CD68 and negative for S-100 and CD1a. Further investigation revealed retro-orbital masses, osteosclerosis of the distal long bones, pleural and pericardial effusion, diabetes insipidus and retroperitoneal fibrosis. Therefore, the patient was diagnosed with Erdheim-Chester disease. A BRAF V600E mutation was confirmed and vemurafenib (1920 mg/day) was initiated. However, three weeks later the patient developed DRESS syndrome and the treatment was stopped. After multidisciplinary discussion, it was decided to begin treatment with cobimetinib (40 mg/day). A clinically and radiographically (assessed with 18F-FDG PET) significant improvement was noted after three months of therapy. Erdheim-Chester disease is a non-Langerhans cell histiocytosis with possible cutaneous involvement. Diagnosis is challenging and should be suspected in the presence of xanthelasma-like lesions and signs of a multisystem disease. Since 2012 with discovery of BRAF mutations in about 50% of patients, BRAF inhibitors have become a first-line treatment. More recently, cobimetinib, a MEK inhibitor, has been used in patients with BRAF wild-type disease, or in who cannot tolerate or do not respond to vemurafenib. To the best of our knowledge, we report herein the first case of Erdheim-Chester disease evaluated by confocal microscopy.

P42 Use of trametinib, a MEK1 inhibitor, to treat Erdheim Chester disease (ECD)

Abstract Background Erdheim Chester disease (non-Langerhan’s cell histocytosis) is a poorly recognised rare multisystem disorder. Alfa interferon (αINF) is recommended as initial therapy. BRAFV600E and MAP2K1 mutations have been identified in this condition, for which targeted biologic therapy is now available. We present a clinically challenging case of ECD, including both small and large vessel vasculitis, intolerant of αINF, who has now responded well to MAP2KI inhibition. Methods A 49-year-old gentleman was referred to the rheumatology clinic in 2013 with a multisystem inflammatory condition, initially characterised by weight loss, systemic upset, cranial diabetes insipidus and hypogonadism, testicular masses, lymphadenopathy and knee arthritis. Initial PET scan demonstrated uptake in these areas, together with the typical long bone pattern of uptake of ECD with complete enhancement of the pituitary on MRI. Non-Langerhan’s cell histocytosis was confirmed histologically from synovial biopsy, with presence of the MAP2K1 mutation. He was initially treated with αINF, which he was unable to tolerate, and he was then maintained on a combination of subcutaneous methotrexate and prednisolone. In 2017, he developed transient weakness and dysarthria, and episcleritis with DSA-MRI consistent with small vessel cerebral vasculitis. This was treated with cyclophosphamide. 6 months later, he experienced amaurosis fugax. He was found to have critically stenotic carotid arteries, despite these being normal when imaged 6 months previously. Carotid artery biopsy confirmed non-giant cell vasculitic changes, and PET confirmed large vessel uptake from carotids to aortic arch. Results Funding for targeted biologic therapy was turned down by NHSE. Trametib, a MEK1 inhibitor was obtained on compassionate grounds. Following commencement of this, PET uptake in all areas, including the vasculature normalised, with symptomatic resolution and CRP falling from 148 to 4. At the 6-month point, he remains in remission symptomatically, radiographically and in laboratory markers. Conclusion ECD is a rare multi-system disorder characterised by tissue infiltration of foamy histiocytes. There are approximately 550 cases described in the literature. It is classified as an inflammatory myeloid neoplasm, with variable phenotype and prognosis. Median survival is 162 months. CNS involvement and lack of response to α-INF are both independent predictors of a poor prognosis. Two genetic mutations have been identified in these patients: BRAFV600E in over 60% and MAP2K1 in 20%. Both mutations now have targeted biologic inhibition. ECD may present in the rheumatology clinic due to its inflammatory and multisystem involvement. We hope to promote recognition of this condition through this case. Although targeted therapies exist, better avenues of funding need to be available for patients with rare conditions to access them. Disclosures H. Alkoky None. T. Munir None. F. Borg None.

A rare case of non-Langerhans cell histiocytosis/ Erdheim-Chester disease presenting as desquamative gingivitis and oral mucosal erythema

Background Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by BRAFV600 E mutations in greater than 50% of patients; multisystemic involvement, such as skin (xanthelasma); heart (pericardial effusion); central nervous system (brain-stem lesions); and bone lesions. ECD has a distinct histopathology and immunochemistry profile, which is negative for CD1 a, S100, and Langerin. Craniofacial involvement has been reported in less than 10 cases and described as multiple, solitary, well-defined radiopaque/lucent lesions of the jaws. We report a case of ECD, which initially included desquamative gingivitis, mucosal erythema, and edema. Case Summary A 62-year-old white woman was referred by her local dentist to the Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, in December 2017, with the chief complaint of mouth sensitivity. Her medical history was notable for a 7-year history of intermittent bone pain, nonpruritic, erythematous, papular rashes of the neck, extremities, and trunk, as well as gingival erythema. She was diagnosed with ECD by a hematologist–oncologist in December 2010 based, in part, on tibial biopsy and the presence of BRAFV600 E mutation. Her medications included prednisone 40 mg 4 times daily by mouth, Bactrim 4 times daily by mouth, subcutaneous MTX 27.5 mg weekly injection, and dabrafenib 150 mg every 12 hours. She reported having a 10-year history of intermittent sensitivity, redness, and swelling of the gingiva, without any known triggers or patterns. On oral examination, there was diffuse desquamation, erythema, and edema of the buccal and palatal gingivae, as well as erythema of the mid–hard palatal mucosa. Differential diagnoses were ECD, vesiculobullous disorders, and vasculitis. With the patient's consent, an incisional biopsy specimen was obtained, and histopathology revealed the presence of chronic inflammation and a scant histiocytic infiltrate. The patient was managed with topical clobetasol 0.05% via custom trays to the maxilla and the mandible; the patient reported a greater than 75% improvement in sensitivity score after 1 month of use. Five months later, she presented with 2 erythematous nodules (#12 and #19), which were consistent with pyogenic granulomas on excisional biopsy. Conclusions This is the first report of potential oral mucosal involvement of ECD, with the noted desquamative gingivitis and erythema as its oral presentation.

Abstract #210 Pituitary and Bone Abnormalities in a 55-Year-Old Man: A Case of Erdheimchester Disease with Braf V600 Mutation

Abstract #210 Pituitary and Bone Abnormalities in a 55-Year-Old Man: A Case of Erdheimchester Disease with Braf V600 Mutation

A case of Erdheim-Chester disease

Erdheim-Chester病（Erdheim-Chester disease，ECD）是一种罕见的非朗格汉斯细胞组织细胞增生症，其临床表现异质性高，从无症状骨病变到危及生命的多脏器功能衰竭均可出现。本文报道1例以全身骨痛、心包积液、肺内结节为主要表现并经骨骼病理确诊的ECD，经干扰素α治疗后患者全身骨痛缓解且C反应蛋白水平下降。.

A RARE CASE OF ERDHEIM-CHESTER DISEASE MASQUERADING AS METASTATIC LUNG CANCER

SESSION TITLE: Lung Cancer 3 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Erdheim-Chester Disease (ECD) is a non-Langerhans histiocytosis characterized by xanthomatous infiltration by CD68 positive, CD1a and S100 negative foamy histiocytes causing multi-system involvement. It was first identified in 1930, however, there have only been approximately 500 reported cases. Concomitant pituitary involvement, multiple axial skeletal lesions, and lung involvement is suggestive of ECD. Diagnosis typically involves histopathological studies in the appropriate clinical and radiological context. Here we present a case of ECD diagnosed during investigation of diabetes insipidus (DI) and a lung mass. CASE PRESENTATION: A 63-year-old female with a history of hyperlipidemia presented to the Endocrinology clinic for evaluation of polydipsia which was later diagnosed as DI. Extensive serum evaluation for etiology was unremarkable. MRI brain showed thickened infundibulum with increased enhancement suggestive of an inflammatory or infiltrative process. As part of her routine health maintenance, she had CTA coronaries done which showed a 2.1 cm spiculated left lung mass. Further investigations with repeat chest CT, PET scan and a bone scan confirmed malignant appearing left lung lesion along with body-wide skeletal lesions involving bilateral femurs, tibias, and left humerus, concerning for metastatic lung cancer. She underwent biopsy of the lung mass followed by lobectomy. Pathology findings were consistent with adenocarcinoma of the lung with immunostaining positive for TTF-1 and napsin-A. Subsequently, the patient underwent open biopsy of the left humeral lesion, which showed extensive fibrosis, focal lymphoplasmacytic infiltration, and scattered histiocytes. Immunostaining was negative for S100 and CD1a and positive for CD68. Pituitary involvement, DI, the presence of multiple skeletal lesions and staining profile is highly suggestive of ECD. Peripheral blood cytometry was positive for BRAF-V600 mutation. We are awaiting tissue studies for mutational analysis prior to treatment initiation. DISCUSSION: Patients with ECD are usually males of age 40-70 years; our patient had atypical features with female gender and late age of onset. DI associated with pituitary stalk thickening represents the most common neurological symptom, along with long bone involvement. Given the rarity of the disease, there are no clear guidelines regarding treatment approach; consensus guidelines recommend a treatment tailored for organ predominance and clinical severity to help facilitate treatment of “high risk” groups. CONCLUSIONS: Currently, the 5-year survival is less than 70%. However, the discovery of activating mutations of BRAF in 54% of the ECD patients has led to a modified therapeutic approach. A recent study suggests Vemurafenib (BRAF inhibitor) has prolonged efficacy in patients with BRAF V-600 mutant ECD and warrants consideration as the new standard of care for these patients. Reference #1: Cives, M., Simone, V., et.al. (2015). Erdheim–Chester disease: A systematic review. Retrieved March 03, 2018, from https://doi.org/10.1016/j.critrevonc.2015.02.004 Reference #2: Diamond, E. L., Subbiah, V., et.al. (2017). Vemurafenib for BRAF V600-Mutant Erdheim-Chester Disease and Langerhans Cell Histiocytosis: Analysis of Data From the Histology-Independent, Phase 2, Open-label VE-BASKET Study. Retrieved March 03, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/29188284 DISCLOSURES: No relevant relationships by Nayla Ahmed, source=Web Response No relevant relationships by Ayushi Chauhan, source=Web Response No relevant relationships by Prashant Grover, source=Web Response No relevant relationships by Joerg Rathmann, source=Web Response No relevant relationships by Parin Shah, source=Web Response No relevant relationships by Aniket Sharma, source=Web Response No relevant relationships by John Thayer, source=Web Response

ERDHEIM-CHESTER DISEASE: A RARE ENTITY

SESSION TITLE: Lung Cancer 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis of unknown origin. Its presentation can vary from asymptomatic bone lesions to multiorgan involvement. We describe a case of ECD with central nervous system (CNS), pulmonary, renal and retro-orbital involvement. CASE PRESENTATION: Sixty five year-old man with medical history significant for myelodysplastic syndrome (MDS) complicated by vascular events, chronic kidney disease, initially presented with severe headache and episode of fall, 20 lbs weight loss, multiple infections, recent bacteremia. During that admission, craniotomy done for possible subdural hematoma revealed extensive masses which were biopsied. He was discharged to an acute rehab but subsequently readmitted for progressive weakness.On admission, patient had thin extremities, distended abdomen, dependent pitting edema, rales in lung bases, splenomegaly, exophthalmos. CT Chest was significant for diffuse, marked interlobular septal thickening, ground glass opacities. New lucent lesions were identified on L1 vertebrae. MRI brain showed brain frontoparietal lesions upto 4 mm with mass effect for whichdecadrom was started. Eventually final pathology confirmed Non-Langerhans Histiocytosis along with positive BRAF V600E mutation. Vemurafenib was started, and patient’s initial symptoms of weakness improved. DISCUSSION: ECD is a rare form of non-Langerhans cell histiocytosis characterized by infiltration of lipid-laden histiocytes with foamy or eosinophillic cytoplasm to various organs along with specific immunohistochemistry pattern – CD68 positive and CD1a negative.(1) Mean age of presentation is at 53. Common clinical presentations include bone pain, fever and weight loss. About half of the patients will have extraosseous involvement of the disease, including the pericardium, exophthalmos, diabetes insipidus, CNS and pulmonary involvement. Both CNS and cardiac involvement carry poor prognosis.Pulmonary lesions in ECD are considered to be from histiocytic infiltration of pulmonary tissue.(2) Diagnosis is based in demonstration of histiocytes with characteristic immunohistochemistry pattern with supportive clinical and radiological findings. BRAF V600E mutation is demonstrated in about half of the patients. Interferon α and peginterferon α-2a are the most commonly used first line agent. Other agents like anakinra, toclizumab, infliximab and cladribine have been used with mixed response. In a recent case series targeted therapy with vemurafenib in patients with BRAF V600E mutation have shown promising results.(3) CONCLUSIONS: ECD is a rare disorder with wide spectrum of presentation. Diagnosis is based in demonstration of histiocytes with characteristic immunohistochemistry pattern with supportive clinical and radiological data. Vemurafenib has shown promising results in patient subset with BRAF V600E mutation. Reference #1: Cives M, Simone V, Rizzo FM, et al. Erdheim-Chester disease: a systematic review. Crit Rev Oncol Hematol. 2015;95(1):1-11. Reference #2: Mazor RD, Manevich-mazor M, Shoenfeld Y. Erdheim-Chester Disease: a comprehensive review of the literature. Orphanet J Rare Dis. 2013;8:137. Reference #3: Haroche J, Cohen-aubart F, Emile JF, et al. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol. 2015;33(5):411-8. DISCLOSURES: No relevant relationships by Mridul Gupta, source=Web Response No relevant relationships by Becky Lou, source=Web Response No relevant relationships by Luis Quintero, source=Web Response No relevant relationships by Effie Singas, source=Web Response

A case of Erdheim-Chester disease with spinal cord compression and sphenoid sinus involvement

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis. It is an inflammatory disorder associated with BRAF V600E mutation in 50% of cases. This multisystem disease is rarely associated with spinal involvement. Neurological involvement is an independent predictive factor of poor prognosis. The diagnosis is histopathological based on CD68-positive and CD1A-negative histiocytes. Treatment with interferon-alpha is an independent predictor of survival in Erdheim-Chester disease and vemurafenib has also been shown to be effective for BRAF V600E mutation. We report a clinical case of a 51-year-old patient with multiple and rare locations of Erdheim-Chester disease, particularly at the sphenoid sinus.

A Case of Erdheim-Chester Disease Developed during Treatment of Leukemiain a Child

A Case of Erdheim-Chester Disease Developed during Treatment of Leukemiain a Child

Solving a Mystery . . . 8 Years Later.

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis with multisystem involvement and insidious symptoms. In this article, we describe an interesting case of Erdheim-Chester disease that was eventually diagnosed 8 years after symptoms initially started.

Erdheim-Chester Disease Involving Lymph Nodes and Liver Clinically Mimicking Lymphoma: A Case Report.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis and multisystem disease. First described in 1930, there are no more than 750 cases reported. The etiology remains unknown, but a majority of cases of ECD and Langerhans cell histiocytosis were found to have clonal mutations involving genes of the mitogen-activated protein kinase pathway. We recently encountered a 53-year-old male patient with extensive ECD involving the systemic lymph nodes, pleura, liver, and long bones clinically mimicking malignant lymphoma. Biopsies were performed at multiple sites, including a pleural mass, an external iliac lymph node, bone marrow, and the liver. Based on histopathological and immunohistochemical findings of positivity for CD68 and negativity for CD1a and S-100, the patient was diagnosed with ECD. Interferon-α was administered as the first-line treatment, but the patient rapidly progressed to hepatic failure after 2 months of treatment. We report this rare case of ECD clinically mimicking malignant lymphoma and diagnosed by careful pathological review.

An unusual case of interstitial lung disease in a patient with cardiopulmonary syndrome as the initial presentation of Erdheim-Chester disease

Erdheim-Chester disease (ECD) is a very rare disorder with only approximately 600 cases reported in the literature. ECD has been recently reclassified as a histiocytic dendritic cell neoplasm. The clinical...

Erdheim-Chester Disease with No Skeletal Bone Involvement and Massive Weight Loss

Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell histiocytosis, with only 550 cases reported worldwide. ECD is characterized by diffuse histiocytic infiltration of multiorgans. The age of presentation of this disease is typically between 40 and 70 years. Bone disease is the most common symptom, as unique radiological findings of long bone sclerosis occur in 96% of cases. Furthermore, BRAF V600E mutation is detected in 60% of ECD cases. In this manuscript, we are describing a unique case of ECD; the patient is younger than most reported cases and has no bone pain or any skeletal involvement. This patient has unintentionally lost about 50% of his body mass and is suffering from progressive cerebellar manifestations with radiological evidence of cerebellar atrophy, in contrast to the usual ECD manifestation of cerebellar infiltration. In addition, the patient has cardiac, retroperitoneal, and perinephric involvement, but he retains his sexual drive and fertility. A tissue biopsy from the retroperitoneal mass displayed typical morphological and immunohistochemical features of ECD, and BRAF V600E mutation was detected. He was treated with pegylated interferon alpha, but his disease progressed and the treatment was changed to vemurafenib to which he had an excellent response at 6 weeks.

A case of Erdheim Chester disease with central nervous system involvement

Erdheim Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, commonly involving the musculoskeletal system. Other tissue can also be involved, including the central nervous system with wide spectrum of clinical features, at times being nonspecific. This can cause diagnostic dilemmas with delay in diagnosis and initiation of therapy. Here we describe a 63-year-old man who had presented with ataxia and behavioral changes, bony pains, weight loss, and fatigue. His computed tomography (CT), 99Tc scintigraphy and histopathological features on bone biopsy were consistent with ECD. Thus, ECD should be considered as a differential diagnosis in patients presenting with bony pain and nonspecific features of multiorgan involvement.

A Rare Case of Erdheim-Chester Disease and Langerhans Cell Histiocytosis Overlap Syndrome.

A 48-year-old woman with a past medical history of seizures and end-stage renal disease secondary to obstructive uropathy from retroperitoneal fibrosis presented to the emergency department with seizures and altered mental status. A Glasgow Coma Scale of 4 prompted intubation, and she was subsequently admitted to the intensive care unit. Magnetic resonance imaging of the brain performed to elucidate the aetiology of her seizure showed a dural-based mass within the left temporoparietal lobe as well as mass lesions within the orbits. Further imaging showed extensive retroperitoneal fibrosis extending to the mediastinum with involvement of aorta and posterior pleural space. Imaging of the long bones showed bilateral sclerosis and cortical thickening of the diaphyses. Imaging of the maxillofacial structures showed osseous destructive lesions involving the mandible. These clinical and radiological features were consistent with a diagnosis of Erdheim-Chester disease; however, the patient's skin biopsy was consistent with Langerhans cell histiocytosis.

抗ヒトTNF-αモノクローナル抗体製剤(インフリキシマブ)により皮下腫瘤の増大抑制効果が得られたErdheim-Chester病の1例

抗ヒトTNF-αモノクローナル抗体製剤(インフリキシマブ)により皮下腫瘤の増大抑制効果が得られたErdheim-Chester病の1例

A Case of Erdheim-Chester Disease with Diplopia

A Case of Erdheim-Chester Disease with Diplopia

One case of Erdheim-Chester disease with onset as diabetes insipidus

患者女性,51岁,因多饮、多尿10年,面部、颈部脓疱15天于2012年4月28日入院.入院前10年,患者无明显诱因出现多饮、多尿,诊断尿崩症,MRI检查示垂体病变,考虑垂体瘤,于广州某医院行γ刀治疗,随后长期口服醋酸去氨加压素片治疗.入院前6年因眩晕于重庆某医院行头颅CT检查示右侧胆脂瘤,右侧颞骨骨质局限性破坏,考虑胆脂瘤,行右耳完璧式乳突根治术+外淋巴瘘修补术,术后病检结果为肉芽肿性炎.入院前2年随访MRI发现垂体病变增多,在北京某医院行经蝶垂体组织部分切除术,术后病检见垂体多种细胞,考虑为正常垂体组织.入院前8个月,

Erdheim‐Chester disease with prominent pericardial effusion

Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown origin with distinct clinicopathologic and radiographic features. Reports detailing the cytology of ECD are rare. We describe a case of ECD with pericardial effusion. Cytologic examination revealed a hypercellular specimen composed of clusters and singly dispersed foamy macrophages with round nuclei and inconspicuous nucleoli, admixed with lymphocytes, eosinophils, and Touton-type multinucleated giant cells. Immunostains for CD68 were strongly positive in the foamy macrophages while S100 and CD1a were negative. The presence of foamy histiocytes, multinucleated giant cells, lymphocytes and eosinophils are also features of other systemic histiocytic disorders, including Langerhans cell histiocytosis (LCH), Rosai-Dorfman disease (RDD) and sarcoidosis. To the best of out knowledge, this is the first report describing the cytological features of ECD in a pericardial effusion.