scholarly journals Dramatic response to encorafenib in a patient with Erdheim–Chester disease harboring the BRAF V600E mutation

2021 ◽  
Author(s):  
Fumiya Wada ◽  
Nobuhiro Hiramoto ◽  
Daisuke Yamashita ◽  
Shigeo Hara ◽  
Yutaka Furukawa ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Braf V600e ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

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.

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

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 571-578 ◽  
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.

Erdheim-Chester Disease Harboring the BRAF V600E Mutation

2012 ◽  
Vol 30 (32) ◽  
pp. e331-e332 ◽  
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

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

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 571-578 ◽  
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.

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

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Hind Salama ◽  
Suleiman Kojan ◽  
Shaima Abdulrahman ◽  
Fahad Azzumeea ◽  
Ayman Alhejazi
Keyword(s):  
Cerebellar Atrophy ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Long Bone ◽  
Common Symptom ◽  
Rare Type ◽  
Skeletal Involvement ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

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.

scholarly journals Evaluation of Clinicopathologic Characteristics and the BRAF V600E Mutation in Erdheim-Chester Disease Among Chinese Adults

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3870-3870
Author(s):  
Xin-xin Cao ◽  
Jian Sun ◽  
Jian Li ◽  
Ding-rong Zhong ◽  
Na Niu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Disease Duration ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Radiographic Findings ◽  
Erdheim Chester Disease ◽  
Rosai Dorfman Disease ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Objectives Erdheim-Chester disease (ECD) is a rare form of histiocytosis with a broad, non-specific clinical spectrum. Here, we retrospectively evaluated the clinical and pathologic characteristics, presence of the BRAF V600E mutation, treatment options and outcomes of Chinese patients diagnosed with ECD at our center. Methods Patients diagnosed with ECD between January 2010 and April 2015 at Peking Union Medical College Hospital were included for study. We evaluated baseline characteristics, reviewed histological material, and tested for the presence of the BRAF V600E mutation using immunohistochemistry and polymerase chain reaction (PCR). Results Sixteen patients were diagnosed with ECD. Median age at diagnosis was 47 years (range, 22-61 years). Median disease duration (from the first symptom to diagnosis) was 22.5 months (range, 3-100 months). The main sites of involvement included bone (93.8%), cardiovascular region (43.8%), skin (31.3%), central nervous system (25.0%), and ¡°hairy kidney¡± (25%). Thirteen patients displayed characteristic histological features, including foamy histiocyte infiltration of polymorphic granuloma and fibrosis or xanthogranulomatosis, with CD68-positive and CD1-¦Á- negative immunostaining. Three patients (designated 3, 5 and 10) displayed CD68-positive and CD1¦Á- negative histiocyte infiltration, but not the above histological characteristics, and were thus initially misdiagnosed as Rosai-Dorfman disease. All three cases were BRAFV600E mutation-positive, leading to revision of diagnosis as ECD. Diagnosis of ECD in each case was additionally supported by typical radiographic findings. The BRAF V600E mutation was detected in 68.8% patients using PCR and 50.0% patients with immunohistochemistry. Ten patients (62.5%) received IFN-¦Á as first-line treatment, 3 patients showed improvement, 3 remained stable, 3 were too early for evaluation and 1 died. Three patients (5, 10 and 11) underwent transsphenoidal pituitary lesion surgery but were not subjected to systemic treatment, owing to the absence of symptoms and disease activity post-surgery and remained stable after a median of 16 months (range, 6-30 months) from diagnosis. Thirteen patients (81.3%) were still alive at median follow-up of 14.5 months. Conclusion ECD remains a largely overlooked disease, and increased recognition by clinicians and pathologists is necessary for effective diagnosis and treatment. The presence of the BRAF V600E mutation may facilitate discrimination of ECD from other non-Langerhans cell histiocytoses. Table 1. Characteristics and treatment of 16 patients with ECD Patient Sex/ age, years Disease duration, mo Main sites of involvement BRAF IH BRAF V600E Therapy Vital Status OS£¬mo 1 M/33 5 B N/A - IFN-6 MIU 3/wk Alive 15 2 M/22 43 S, B - - IFN-3 MIU 3/wk Alive 11 3 M/25 18 B, LN, CNS - + Pred Dead 13 4 F/28 3 S, B + + None Alive 16 5 M/60 27 B, PIT + + Surgery Alive 15 6 F/61 5 B, H, LV, R£¬CNS, MS, S N/A + IFN-6 MIU 3/wk Dead 25 7 F/23 67 S, B, H, LV - - IFN-3 MIU 3/wk Alive 19 8 M/60 43 B, P, LV, R N/A + IFN-6 MIU 3/wk Alive 14 9 M/46 84 CNS, B + + IFN-6 MIU 3/wk Alive 22 10 F/51 7 PIT + + Surgery Alive 6 11 F/36 72 PIT, B + + Surgery Alive 30 12 M/55 100 B, S, CNS, PIT - + IFN-6 MIU 3/wk Alive 3 13 F/50 11 B, H N/A + IFN-6 MIU 3/wk Alive 5 14 F/46 8 B, LV, P + + IFN-6 MIU 3/wk Alive 1 15 M/52 30 B, LV, R, P£¬E - - IFN-6 MIU 3/wk Alive 1 16 M/47 4 B, LV, R, LN - - None Dead 36 Age is at diagnosis£»disease duration is from the first symptom to diagnosis IH, immunohisochemistry; B, long bones; LN, lymph nodes; LV, large vessels; H, heart; S, skin; CNS, central nervous system; MS, maxillary sinus; PIT, pituitary gland; R, retroperitoneal; P, pericardial effusion; E, Exophthalmos; MIU, million international units; N/A, not available Disclosures No relevant conflicts of interest to declare.

scholarly journals Relevant Imaging Presentation of Erdheim-Chester Disease: A case-report

2018 ◽  
Vol 13 (2) ◽  
Author(s):  
Philippe Jacob
Keyword(s):  
Bone Pain ◽  
Clinical Manifestations ◽  
Braf Inhibitor ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Bone Lesions ◽  
Erdheim Chester Disease ◽  
Promising Treatment ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans multisystemic histiocytosis. This disorder is characterised by CD68+/CDa1- foamy histiocytes infiltration in tissues, especially bones, retroperitoneum, heart, lung and brain. Clinical manifestations may range from asymptomatic bone lesions to multiorganic symptoms. Bone pain in lower extremities are however the most common symptoms. Typical imaging findings include symmetric dyaphyseal osteosclerosis of long bones, periaortic sheathing (“coated aorta”) and retroperitoneal infiltration (“hairy kidney”). Lung and brain radiological abnormalities may also be seen on imaging screening. BRAF-V600E mutation is associated with around half of ECD patients. Vemurafenib, a mutated BRAF inhibitor, is a promising treatment for patients with this mutation. We present the case of a 60 years old man who arrived with a pathological right humerus fracture, and who was first admitted for a tuberculosis suspicion. ECD was first suspected with imaging screening.

Erdheim–Chester disease with an 18F-fluorodeoxyglucose-avid breast mass and BRAF V600E mutation

2014 ◽  
Vol 32 (5) ◽  
pp. 282-287 ◽  
Author(s):  
Toshihiro Furuta ◽  
Shigeru Kiryu ◽  
Haruyasu Yamada ◽  
Masataka Hosoi ◽  
Mineo Kurokawa ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Braf V600e ◽  
Breast Mass ◽  
18F Fluorodeoxyglucose ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Irrwege der Diagnostik – Erdheim-Chester Disease (ECD) mit Nachweis einer BRAF-V600E-Mutation

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S81-S81
Author(s):  
S Görlitz ◽  
T Tiedje ◽  
H Berger ◽  
K Junker ◽  
J Rose ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Braf V600e ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

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.

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