Erdheim-Chester disease presenting as a intracardiac mass and pericardial effusion confirmed by biopsy: a case report

Abstract Background Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that can affect the bones, heart, lungs, brain, and other organs. Cardiovascular involvement is common in ECD and is associated with a poor prognosis. Here, we report a case of ECD presenting as a intracardiac mass and pericardial effusion confirmed by biopsy with sternotomy. Case summary A 54-year-old man was admitted because of dyspnoea. He was previously diagnosed with bilateral hydronephrosis and retroperitoneal fibrosis. Echocardiography revealed a large amount of pericardial effusion and echogenic mass on the right atrial (RA) side and atrioventricular (AV) groove. Cardiac magnetic resonance imaging and positron emission tomography-computed tomography (CT) revealed infiltrative mass-like lesions in the RA and AV groove. Pericardial window formation and pericardial biopsy were performed, and the pathologic results showed only pericardial fibrosis with no specific findings. Bone scan revealed increased uptake in the long bones. Considering the high probability of ECD based on the patient’s manifestations and the imaging findings, we performed a cardiac biopsy with median sternotomy despite initial insufficient pathologic results in the pericardial biopsy. The surgical findings included multiple irregular and firm masses on the cardiac wall and large vessels; after obtaining a large amount of suspicious mass, ECD accompanied with CD68 (+) and BRAF V600E mutation was confirmed. Discussion ECD can be associated with various forms of cardiovascular involvement. Considering the multi-systemic manifestations and difficulty in identifying this rare disease, a comprehensive and meticulous diagnostic work-up is crucial.

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Correlation of BRAF V600E mutation with cardiac involvement assessed by heart imaging in a monocentric series of 205 patients with Erdheim-Chester disease.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.7019 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 7019-7019 ◽

Cited By ~ 1

Author(s):

Marine Bravetti ◽

Levi-Dan Azoulay ◽

Fleur Cohen-Aubart ◽

Jean-François Emile ◽

Zahir Amoura ◽

...

Keyword(s):

Cardiac Imaging ◽

Cardiac Involvement ◽

Braf V600e ◽

Myeloid Neoplasm ◽

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

The Right ◽

Pericardial Involvement ◽

Erdheim Chester ◽

Chester Disease

7019 Background: Erdheim–Chester disease (ECD), an inflammatory myeloid neoplasm, is an histiocytosis associated with multisystem infiltration. Cardiovascular involvement in ECD is under-diagnosed and associated with poor outcome. The targetable BRAFV600Emutation is present in up to 70% of all ECD. Methods: Retrospective study of 205 patients (pts) with ECD who had cardiac imaging (195 MRI, 10 CT when MRI was contraindicated). We identified the types of lesions (infiltration, tumor, and effusion), localization (pericardial, myocardial, valvular) and consequences on cardiac function (coronary stenosis, atrial wall dyskinesia, diastolic and systolic functions). Results: 141 (68.8%) pts were male. 30 (14.6%) had mixed histiocytosis (mainly ECD + langerhans cell histiocytosis). BRAF mutation ( BRAFm) was found in 112 (54.6%) cases, while 59 pts (28.8%) were Wild Type (WT) and 34 pts (7.6%) had unknown BRAF status. Among the 205 cardiac imaging, 101 (49.3%) were abnormal. Cardiac involvement was found in 93 pts (49%). Among these, 72 had an impairment of the right ventricular atrioventricular sulcus (74%), 65 of the right atrium (RA) enclosure (69%). Alteration of Tricuspid Annular Plane Systolic Excursion was found in 15% and correlated with the size of the tumor. Pericardial involvement (effusion, thickening or contrast enhancement) was found in 59 pts (29%). Among BRAFm pts, 75 (67%) had a heart abnormality while 37 (33%) had normal imaging; Among WT pts 14 (23.7%) showed heart abnormality, whereas 45 (76.3%) had normal imaging (RR 2.8 (CI: 1.8-4.5); p = 1.8*10-7). A RA tumor was present in 51 (45.5%) BRAFm but only 6 (10.2%) WT pts respectively (RR 4.5 (CI : 2.0-9.8); p = 7*10-6). BRAFm was also associated with aortic infiltration (RR 1.76 (CI: 1.2–2.5)) and pericardial involvement (RR 2.12 (CI: 1.1–3.9), p = 0.0017). Conclusions: Cardiac infiltration is frequent in ECD (49.3%), especially RA tumor. BRAFm is associated with RA, aortic and pericardial involvements.

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P37 Erdheim-Chester disease: an ultra-rare mimic of IgG4-related disease

Rheumatology ◽

10.1093/rheumatology/keaa111.036 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

John S McLaren ◽

Victoria Campbell ◽

Maeve Rahilly ◽

Javed M Rehman ◽

Robert Cargill

Keyword(s):

Pericardial Effusion ◽

Metastatic Carcinoma ◽

Braf V600e ◽

Whole Body ◽

Bone Lesions ◽

Erdheim Chester Disease ◽

Sclerotic Bone ◽

Sclerotic Bone Lesions ◽

Erdheim Chester ◽

Chester Disease

Abstract Background A 56 year old female was hospitalised in July 2019 with abdominal pain and significant weight loss, but little in the way of bone pain. Examination showed no evidence of xanthelasma. A large pericardial effusion was detected, requiring pericardiocentesis. The pericardial fluid contained numerous macrophages staining with CD68. Methods CT scans were reported as consistent with metastatic carcinoma. There were multiple sclerotic bone lesions in the manubrium, T7, T11, L2 and L4. She also had a periaortitis with soft tissue infiltrate around the ascending aorta and aortic arch, in the mediastinum, posterior paravertebral region, and in the retroperitoneum, obscuring both adrenal glands and surrounding both kidneys. Bone marrow aspirate and trephine demonstrated reactive appearances only. Results She required re-admission with breathlessness due to recurrence of the pericardial effusion. Biopsy from the left perinephric region was performed. Histopathology revealed a fibroinflammatory disorder. Some histiocytes were seen. There was no evidence of the typical features of IgG4-RD such as storiform fibrosis or obliterative phlebitis, which had been the working diagnosis thus far. Serum IgG4 level was normal. The classical histological features of Erdheim-Chester disease (ECD, an ultra-rare non-Langerhans cell Histiocytosis) in terms of foamy macrophages and Touton cells, were not obvious, but in the literature, it is not uncommon for the typical histological appearances of ECD to be absent. Further investigation demonstrated the classical radiographic findings of ECD with symmetrical sclerotic lesions in the long bones of the lower limbs. Radionuclide bone scan showed multifocal symmetrical increase in isotope uptake, predominately in the distal femora, proximal and distal tibiae, mandible and maxillae with multiple lesions in the thoracic and lumbar spine. Endocrine failure is frequently seen in ECD. Fortunately, our patient had neither pituitary disease nor hypoadrenalism. Furthermore, CNS involvement, ataxia and retro-orbital disease have all been reported in ECD. Our patient has experienced daily episodes of right retro-orbital pain, dizziness on upward gaze without diplopia, and occasional staggering. An MRI of brain, orbits and whole spine is scheduled, as are a whole body FDG-PET scan and cardiac MRI (to exclude myocardial infiltration). BRAF V600E mutation analysis is in progress since around 50% of ECD patients with this mutation may respond to vemurafenib treatment. Conclusion In this illustrative case, the combination of a fibroinflammatory disorder surrounding both kidneys, along with recurrent pericardial effusion and sclerotic bone lesions, was clinically and radiologically diagnostic of Erdheim-Chester disease. ECD is a recognised mimic of IgG4-RD, which itself is a mimic of multiple other conditions, including metastatic carcinoma. We present this case to highlight this little-known condition. Rheumatologists and Physicians should consider ECD in the differential diagnosis of IgG4-RD, periaortitis, pericardial effusion, symmetrical sclerotic bone lesions, endocrine failure and neurological features. Disclosures J.S. McLaren None. V. Campbell None. M. Rahilly None. J.M. Rehman None. R. Cargill None.

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Erdheim-Chester Disease: The Importance of Information Integration

Case Reports in Oncology ◽

10.1159/000477658 ◽

2017 ◽

Vol 10 (2) ◽

pp. 613-619 ◽

Cited By ~ 5

Author(s):

Anna Nikonova ◽

Khashayar Esfahani ◽

Guillaume Chausse ◽

Stephan Probst ◽

Tina Petrogiannis-Haliotis ◽

...

Keyword(s):

Retroperitoneal Fibrosis ◽

Braf V600e Mutation ◽

Braf V600e ◽

High Dose ◽

Related Disease ◽

Igg4 Related Disease ◽

Erdheim Chester Disease ◽

History Of ◽

Erdheim Chester ◽

Chester Disease

Background: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis disorder that utilizes the RAS-RAF-MEK-ERK pathway. It has a highly variable clinical presentation, where virtually any organ can be involved, thus having the potential of posing a great diagnostic challenge. Over half of the reported cases have the BRAF V600E mutation and have shown a remarkable response to vemurafenib. Case Presentation: We describe herein a patient with a history of stroke-like symptoms and retroperitoneal fibrosis that on initial pathology raised the possibility of IgG4-related disease. However, the patient was refractory to high-dose steroids and progressed further, developing an epicardial soft tissue mass and recurrent neurological symptoms. Integration of the above findings with new information at another hospital about a radiological history of symmetrical lower extremities long bone lesions raised the differential diagnosis of ECD. Molecular analysis of formalin-fixed paraffin-embedded tissue of both of the patient’s retroperitoneal biopsies (the second one of which had shown a small focus of foamy histiocytes, CD68+/CD1a–) was positive for BRAF mutation, confirming the diagnosis of ECD. The patient demonstrated a dramatic and sustained metabolic response to vemurafenib on follow-up positron emission tomography scans. Conclusion: This case highlights the need for developing a high index of suspicion for presentations of retroperitoneal fibrosis that could represent IgG4-related disease but fail to respond to steroids. When unusual multisystem involvement occurs, one should consider a diagnosis of a rare histiocytosis. Vemurafenib appears to be an effective treatment for even advanced cases of both ECD and Langerhans histiocytosis bearing the BRAF V600E mutation.

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Association of BRAF V600E with Hypothalamic-Pituitary-Adrenal Axis Involvement in Erdheim-Chester Disease

Endocrine and Metabolic Science ◽

10.1016/j.endmts.2020.100051 ◽

2020 ◽

Vol 1 (1-2) ◽

pp. 100051

Author(s):

Fady Hannah-Shmouni ◽

Louisa Boyd ◽

Georgios Z. Papadakis ◽

Amit Tirosh ◽

William A Gahl ◽

...

Keyword(s):

Hypothalamic Pituitary Adrenal Axis ◽

Braf V600e ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Erdheim Chester Disease ◽

Erdheim Chester ◽

Pituitary Adrenal Axis ◽

Chester Disease

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Uncommon histiocytic disorders: Rosai–Dorfman, juvenile xanthogranuloma, and Erdheim–Chester disease

Hematology ◽

10.1182/asheducation-2015.1.571 ◽

2015 ◽

Vol 2015 (1) ◽

pp. 571-578 ◽

Cited By ~ 43

Author(s):

Julien Haroche ◽

Oussama Abla

Keyword(s):

Braf V600e Mutation ◽

Braf V600e ◽

Juvenile Myelomonocytic Leukemia ◽

Juvenile Xanthogranuloma ◽

Poor Prognostic Factor ◽

Erdheim Chester Disease ◽

Recurrent Mutations ◽

Life Threatening ◽

Erdheim Chester ◽

Chester Disease

Rosai–Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and Erdheim–Chester disease (ECD) are non-Langerhans cell (non-LCH) disorders arising from either a dendritic or a macrophage cell. RDD is a benign disorder that presents with massive lymphadenopathy, but can have extranodal involvement. In most cases, RDD is self-limited and observation is the standard approach. Treatment is restricted to patients with life-threatening, multiple-relapsing, or autoimmune-associated disease. JXG is a pediatric histiocytosis characterized by xanthomatous skin lesions that usually resolve spontaneously. In a minority of cases, systemic disease can occur and can be life threatening. Juvenile myelomonocytic leukemia (JMML), as well as germline mutations in NF1 and NF2, have been reported in children with JXG. Recent whole-exome sequencing of JXG cases did not show the BRAF-V600E mutation, although 1 patient had PI3KCD mutation. ECD is an adult histiocytosis characterized by symmetrical long bone involvement, cardiovascular infiltration, a hairy kidney, and retroperitoneal fibrosis. Central nervous system involvement is a poor prognostic factor. Interferon-α is the standard as front-line therapy, although cladribine and anakinra can be effective in a few refractory cases. More than one-half of ECD patients carry the BRAF-V600E mutation. Currently, >40 patients worldwide with multisystemic, refractory BRAF-V600E+ ECD have been treated with vemurafenib, a BRAF inhibitor, which was found to be highly effective. Other recurrent mutations of the MAP kinase and PI3K pathways have been described in ECD. These discoveries may redefine ECD, JXG, and LCH as inflammatory myeloid neoplasms, which may lead to new targeted therapies.

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Biological and Therapeutic Implications of the BRAF Pathway in Histiocytic Disorders

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2014.34.e441 ◽

2014 ◽

pp. e441-e445 ◽

Cited By ~ 12

Author(s):

Robert J. Arceci

Keyword(s):

Dendritic Cell ◽

Braf V600e ◽

Current Evidence ◽

Braf Mutations ◽

Therapeutic Implications ◽

Erdheim Chester Disease ◽

Extracellular Signal ◽

Tumor Protein P53 ◽

Erdheim Chester ◽

Chester Disease

Langerhans cell histiocytosis (LCH) has historically evolved in its classification from a primary immune dysregulatory disorder to what current evidence supports as a dendritic cell neoplasm with an immune-inflammatory component. A key part of the classification of LCH as a neoplasm has been the identification of BRAF V600E mutations in 35% to 60% of cases. Tumor protein p53 (TP53) and RAS mutations have also been identified, albeit in less than 2% of reported cases. Of note, over 50% of patients with another dendritic cell disease, Erdheim-Chester Disease, have also been shown to have BRAF V600E mutations. Although the BRAF mutations have not been shown to be associated with extent of disease, they may still provide a target for a molecularly guided approach to therapy. In cases of LCH in which no BRAF mutations were identified, there was evidence for activation of the RAS-RAF-MEK-extracellular signal-regulated kinases (ERK) pathway, suggesting that similar to other tumors, this pathway may be therapeutically exploitable. Anecdotal responses have been reported in a few patients with LCH and Erdheim-Chester Disease to vemurafenib, a BRAF V600E inhibitor. Although these results pave the way for careful, prospective clinical testing, selection of the optimal groups in which to test such inhibitors, alone or in combination, will be critical based on the toxicity profile thus far observed in adults with melanoma and other BRAF mutated tumors.

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Erdheim-Chester Disease Harboring the BRAF V600E Mutation

Journal of Clinical Oncology ◽

10.1200/jco.2012.43.2260 ◽

2012 ◽

Vol 30 (32) ◽

pp. e331-e332 ◽

Cited By ~ 32

Author(s):

Piers Blombery ◽

Stephen Q. Wong ◽

Stephen Lade ◽

H. Miles Prince

Keyword(s):

Braf V600e Mutation ◽

Braf V600e ◽

Erdheim Chester Disease ◽

Erdheim Chester ◽

Chester Disease

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Erdheim-Chester disease presenting with large pericardial effusion: a mimic of disseminated malignancy

Internal Medicine Journal ◽

10.1111/j.1445-5994.2011.02425.x ◽

2011 ◽

Vol 41 (3) ◽

pp. 291-293 ◽

Cited By ~ 3

Author(s):

P. Jain ◽

N. Jepson ◽

R. Lawford

Keyword(s):

Pericardial Effusion ◽

Erdheim Chester Disease ◽

Large Pericardial Effusion ◽

Erdheim Chester ◽

Chester Disease

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Uncommon histiocytic disorders: Rosai–Dorfman, juvenile xanthogranuloma, and Erdheim–Chester disease

Hematology ◽

10.1182/asheducation.v2015.1.571.3916289 ◽

2015 ◽

Vol 2015 (1) ◽

pp. 571-578 ◽

Cited By ~ 4

Author(s):

Julien Haroche ◽

Oussama Abla

Keyword(s):

Braf V600e Mutation ◽

Braf V600e ◽

Juvenile Myelomonocytic Leukemia ◽

Juvenile Xanthogranuloma ◽

Poor Prognostic Factor ◽

Erdheim Chester Disease ◽

Recurrent Mutations ◽

Life Threatening ◽

Erdheim Chester ◽

Chester Disease

Abstract Rosai–Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and Erdheim–Chester disease (ECD) are non-Langerhans cell (non-LCH) disorders arising from either a dendritic or a macrophage cell. RDD is a benign disorder that presents with massive lymphadenopathy, but can have extranodal involvement. In most cases, RDD is self-limited and observation is the standard approach. Treatment is restricted to patients with life-threatening, multiple-relapsing, or autoimmune-associated disease. JXG is a pediatric histiocytosis characterized by xanthomatous skin lesions that usually resolve spontaneously. In a minority of cases, systemic disease can occur and can be life threatening. Juvenile myelomonocytic leukemia (JMML), as well as germline mutations in NF1 and NF2, have been reported in children with JXG. Recent whole-exome sequencing of JXG cases did not show the BRAF-V600E mutation, although 1 patient had PI3KCD mutation. ECD is an adult histiocytosis characterized by symmetrical long bone involvement, cardiovascular infiltration, a hairy kidney, and retroperitoneal fibrosis. Central nervous system involvement is a poor prognostic factor. Interferon-α is the standard as front-line therapy, although cladribine and anakinra can be effective in a few refractory cases. More than one-half of ECD patients carry the BRAF-V600E mutation. Currently, >40 patients worldwide with multisystemic, refractory BRAF-V600E+ ECD have been treated with vemurafenib, a BRAF inhibitor, which was found to be highly effective. Other recurrent mutations of the MAP kinase and PI3K pathways have been described in ECD. These discoveries may redefine ECD, JXG, and LCH as inflammatory myeloid neoplasms, which may lead to new targeted therapies.

Download Full-text