Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation

Blood ◽  
2013 ◽  
Vol 121 (9) ◽  
pp. 1495-1500 ◽  
Author(s):  
Julien Haroche ◽  
Fleur Cohen-Aubart ◽  
Jean-François Emile ◽  
Laurent Arnaud ◽  
Philippe Maksud ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Tumor Response ◽  
Braf V600e Mutation ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Erdheim Chester Disease ◽  
Key Points ◽  
Erdheim Chester ◽  
Chester Disease

Key Points Treatment with vemurafenib induced a dramatic response in 3 patients with histiocytosis harboring BRAF V600E mutations. Tumor response was observed in both Erdheim-Chester disease and Langerhans cell histiocytosis.

scholarly journals Successful treatment with cladribine of Erdheim-Chester disease with orbital and central nervous system involvement developing after treatment of langerhans cell histiocytosis

2016 ◽  
Vol 73 (1) ◽  
pp. 83-87 ◽  
Author(s):  
Predrag Peric ◽  
Branislav Antic ◽  
Slavica Knezevic-Usaj ◽  
Olga Radic-Tasic ◽  
Sanja Radovinovic-Tasic ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Langerhans Cell Histiocytosis ◽  
Braf V600e Mutation ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Cns Involvement ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Introduction. Erdheim-Chester disease (ECD) is a rare, systemic form of non-Langerhans cell histiocytosis of the juvenile xantho-granuloma family with characteristic bilateral symmetrical long bone osteosclerosis, associated with xanthogranulomatous extras-keletal organ involvement. In ECD, central nervous system (CNS) and orbital lesions are frequent, and more than half of ECD patients carry the V600E mutation of the proto-oncogene BRAF. The synchronous or metachronous development of ECD and Langerhans cell histiocytosis (LCH) in the same patients is rare, and the possible connection between them is still obscure. Cladribine is a purine substrate analogue that is toxic to lymphocytes and monocytes with good hematoencephalic penetration. Case report. We presented a 23-year-old man successfully treated with cladribine due to BRAF V600E-mutation-negative ECD with bilateral orbital and CNS involvement. ECD developed metachronously, 6 years after chemotherapy for multisystem LCH with complete disease remission and remaining central diabetes insipidus. During ECD treatment, the patient received 5 single-agent chemotherapy courses of cladribine (5 mg/m2 for 5 consecutive days every 4 weeks), with a reduction in dose to 4 mg/m2 in a fifth course, delayed due to severe neutropenia and thoracic dermatomal herpes zoster infection following the fourth course. Radiologic signs of systemic and CNS disease started to resolve 3 months after the end of chemotherapy, and CNS lesions completely resolved within 2 years after the treatment. After 12-year follow-up, there was no recurrence or appearance of new systemic or CNS xanthogranu-lomatous lesions or second malignancies. Conclusion. In accordance with our findings and recommendations provided by other authors, cladribine can be considered an effective alternative treatment for ECD, especially with CNS involvement and BRAF V600E-mutation-negative status, when interferon-? as the first-line therapy fails.

Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation

Blood ◽  
2014 ◽  
Vol 124 (7) ◽  
pp. 1119-1126 ◽  
Author(s):  
Baptiste Hervier ◽  
Julien Haroche ◽  
Laurent Arnaud ◽  
Frédéric Charlotte ◽  
Jean Donadieu ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Brafv600e Mutation ◽  
Erdheim Chester Disease ◽  
Key Points ◽  
Erdheim Chester ◽  
Chester Disease

Key Points The association of both Langerhans cell histiocytosis and Erdheim-Chester disease is not exceptional. This association is linked to BRAFV600E mutation.

scholarly journals Pediatric Erdheim-Chester Disease in the Molecular Era: A Multicenter Case Series

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4194-4194
Author(s):  
Francesco Pegoraro ◽  
Elena Gelain ◽  
Stefania Gaspari ◽  
Jean Donadieu ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Langerhans Cell ◽  
Braf V600e ◽  
First Line ◽  
Erdheim Chester Disease ◽  
Sclerotic Bone ◽  
Hypothalamic Pituitary Axis ◽  
Incident Cases ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Background: Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytic disorder that almost exclusively affects adults. Reports of pediatric-onset ECD are only anecdotal. Additionally, a comprehensive clinical and molecular characterization of pediatric ECD is lacking. Methods: All prevalent and incident cases followed at three ECD referral centers in Italy and France were considered eligible when they had: a) an age <18y at disease onset; b) a clinical presentation consistent with ECD (i.e., at least one of the following localizations: bilateral, sclerotic bone involvement; sclerotic bone lesions of facial sinuses; hairy kidneys; coated aorta; xanthelasma; tumoral atrial involvement); c) pathology consistent with ECD or mixed ECD-Langerhans cell histiocytosis (LCH); d) available data on molecular studies. Results: Ten patients were included (4 boys and 6 girls); their median age at diagnosis was 4.5 years (IQR 3-9). Bone pain, diabetes insipidus, and exophthalmos were the predominant clinical manifestations at onset. The most commonly involved sites were the hypothalamic/pituitary axis (8/10, 80%), the maxillary/facial structures (8/10, 80%), the bone (6/10, 60%), and the central nervous system (CNS; 7/10, 70%). Other less frequent localizations included the skin (3/10, 30%), the retroperitoneum (2/10, 20%), the lymph nodes (2/10, 20%), the large vessels (1/10, 10%), the heart (1/10, 10%), and the lung (1/10, 10%). The median number of involved sites was four (IQR 4-4). Four patients (of whom three were younger than nine years) had clinical or pathological features consistent with mixed histiocytosis (ECD-LCH). Molecular analysis of tissue biopsies revealed the BRAF V600E mutation in 6 patients (60%). As compared with adult series, the retroperitoneum, the heart, the lungs, and the skin seemed to be less frequently involved. Conversely, hypothalamic/pituitary and maxillary/facial involvement were apparently more frequent in our pediatric cohort. Treatments were heterogeneous. First-line regimens mainly consisted of chemotherapy deriving from LCH-based regimens: six out of the eight treated patients received chemotherapy, but only two of them achieved a transient response. Interferon-alpha was used in five patients (as first-line treatment in two and as a rescue treatment in three), with a partial response in two. Four patients with the BRAF V600E mutation received the BRAF inhibitor vemurafenib at some point (partial responses were obtained in all, in one case requiring a combination with cobimetinib). All patients were alive at last follow up (median 94 months, IQR 12-108). Chronic sequelae included end-stage kidney disease in one patient, growth retardation in two, and endocrine abnormalities in seven. Conclusions: The clinical phenotype of ECD differs between children and adults. The hypothalamic/pituitary axis and the maxillary/facial area are frequently involved in pediatric cases, whereas other localizations typically seen in adults (i.e., retroperitoneum, heart, lung, and skin) are rarer. An overlap with LCH is frequent, especially in younger patients. As for LCH, targeted treatments can be highly effective in children carrying the BRAF V600Emutation. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Rare Case of Erdheim-Chester Disease (Non-Langerhans Cell Histiocytosis) with Concurrent Langerhans Cell Histiocytosis: A Diagnostic and Therapeutic Challenge

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Hamza Hashmi ◽  
Drew Murray ◽  
John Greenwell ◽  
Marwan Shaikh ◽  
Soumit Basu ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Langerhans Cell Histiocytosis ◽  
Rare Case ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Therapeutic Challenge ◽  
Erdheim Chester Disease ◽  
Organ Systems ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocyte disorder most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocyte infiltrates on biopsy with or without histiocytic infiltration of extraskeletal tissues. ECD can be difficult to diagnose since it is a very rare disease that can affect many organ systems. Diagnosis is based on the pathologic evaluation of involved tissue interpreted within the clinical context. Patients who have the BRAF V600E mutation are treated first line with vemurafenib. For those without the mutation with symptomatic ECD, conventional or PEGylated interferon alpha is recommended. For patients who are either intolerant or nonresponsive to interferon alpha, systemic chemotherapy with or without corticosteroids can be used. We present a rare case of Erdheim-Chester disease with concurrent Langerhans cell histiocytosis which occurs in only one fifth of the cases and often presents as a diagnostic and therapeutic challenge.

scholarly journals Erdheim-Chester Disease: The Importance of Information Integration

2017 ◽  
Vol 10 (2) ◽  
pp. 613-619 ◽  
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.

Erdheim?Chester disease of the breast associated with Langerhans-cell histiocytosis of the hard palate

2004 ◽  
Vol 445 (4) ◽  
pp. 405-409 ◽  
Author(s):  
V. P. Andrade ◽  
C. C. V. Nemer ◽  
A. N. L. Prezotti ◽  
W. S. L. Goulart
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Hard Palate ◽  
Langerhans Cell ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals Dramatic efficacy of dabrafenib in Erdheim-Chester disease (ECD): a pediatric patient with multiple large intracranial ECD lesions hidden by refractory Langerhans cell histiocytosis

2019 ◽  
Vol 23 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Xiaolei Hao ◽  
Ruie Feng ◽  
Yalan Bi ◽  
Yuhan Liu ◽  
Chunde Li ◽  
...  
Keyword(s):  
Pediatric Patient ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Neurological Involvement ◽  
Treatment Processes ◽  
Erdheim Chester Disease ◽  
Intracranial Lesions ◽  
The Central Nervous System ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester disease (ECD) is a rare non–Langerhans cell form of histiocytosis that can affect the central nervous system. ECD predominantly affects adults, and only a few pediatric cases have been reported. The co-occurrence of ECD and Langerhans cell histiocytosis (LCH) is exceedingly rare. An 11-year-old boy, who was diagnosed with LCH 7 years previously, presented with multiple giant intracranial lesions. At the time of his initial diagnosis, only one intracranial lesion was observed, and it began to enlarge. Currently, up to 7 intracranial lesions can be observed in this patient. However, the diagnosis of ECD was not confirmed until this most recent open resection. The BRAF V600E mutation was detected in both LCH and ECD lesions. Dabrafenib therapy exhibited dramatic efficacy in this pediatric patient. This case represents the first successful application of dabrafenib in a pediatric patient with intracranial ECD lesions as well as mixed ECD and LCH. In this article, the authors describe the intricate diagnosis and treatment processes in this patient. Recent studies regarding treatment with BRAF inhibitors for neurological involvement in mixed ECD and LCH are also reviewed.

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