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

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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.

ABBREVIATIONS ECD = Erdheim-Chester disease; FGD = 18F-labeled fluorodeoxyglucose; LCH = Langerhans cell histiocytosis.

Article Information

Correspondence Yongji Tian: Capital Medical University, Beijing, People’s Republic of China. email: ttyysw1tyj@163.com.

INCLUDE WHEN CITING Published online September 28, 2018; DOI: 10.3171/2018.6.PEDS17728.

X.H. and R.F. contributed equally to this work and share first authorship.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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    A: Three-dimensional CT scans of the skull showing osteolytic lesions in the craniofacial bones. B and C: Sagittal and axial T1-weighted MR images obtained 7 years ago. Images show a thickening pituitary stalk, lack of hyperintense signal in the neurohypophysis (B, arrowhead), and a nodular mass with isointense signals located in the trigone of the left lateral ventricle (C, 1.5 × 1.5 × 1.5 cm, arrow). D: Axial T1-weighted Gd-enhanced MR image acquired after the initial chemotherapy. The image shows that the nodular mass with homogeneous intense enhancement is larger now (arrow, maximal diameter 3.0 cm).

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    A: Axial and coronal T1-weighted Gd-enhanced MR images obtained before the recent operation. The images show the mass lesions involving the saddle area (5.8 × 4.7 × 4.5 cm), right lateral ventricle, bilateral frontal and parietal lobes, cerebral falx, and tentorium cerebelli. B: Follow-up MR images acquired after 2 months of dabrafenib therapy. The lesion located in the right parietal lobe was resected completely in the recent operation (arrowhead). The other intracranial mass lesions showed a marked decrease in size (arrows).

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    A: Radiograph of the right tibiofibular and foot bones demonstrating the coexistence of osteolytic and sclerotic changes. B: FDG-PET scan revealing bilateral radiotracer uptake in the ribs, humeri, ilium, and femurs.

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    Photographic and histological studies. A: The ECD lesion resected from the convexity of the right parietal lobe, which has a yellow and solid cut surface. B: The ECD specimen shows foamy histiocytes in a background of fibrosis. H & E, original magnification ×200. Higher-magnification photomicrograph reveals that the foamy histiocytes have bland nuclei and abundant cytoplasm. H & E, original magnification ×400 (inset). C: Immunohistochemical staining shows many of the CD68-immunopositive foamy cells in the ECD specimen. CD68, original magnification ×400. D: The LCH specimen shows Langerhans cells that have coffee bean–shaped nuclei. H & E, original magnification ×200. E and F: These cells reacted positively to CD1a (E) and S100 (F). Figure is available in color online only.



Badalian-Very GVergilio JADegar BAMacConaill LEBrandner BCalicchio ML: Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 116:191919232010


Cohen Aubart FEmile JFCarrat FCharlotte FBenameur NDonadieu J: Targeted therapies in 54 patients with Erdheim-Chester disease, including follow-up after interruption (the LOVE study). Blood 130:137713802017


Diamond ELDagna LHyman DMCavalli GJanku FEstrada-Veras J: Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 124:4834922014


Diamond ELSubbiah VLockhart ACBlay JYPuzanov IChau I: 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. JAMA Oncol 4:3843882018


Emile JFAbla OFraitag SHorne AHaroche JDonadieu J: Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 127:267226812016


Haroche JCharlotte FArnaud Lvon Deimling AHélias-Rodzewicz ZHervier B: High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 120:270027032012


Haroche JCohen-Aubart FRollins BJDonadieu JCharlotte FIdbaih A: Histiocytoses: emerging neoplasia behind inflammation. Lancet Oncol 18:e113e1252017


Hervier BHaroche JArnaud LCharlotte FDonadieu JNéel A: Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood 124:111911262014


Kim SLee MShin HJLee JSuh YL: Coexistence of intracranial Langerhans cell histiocytosis and Erdheim-Chester disease in a pediatric patient: a case report. Childs Nerv Syst 32:8938962016


Laurencikas EGavhed DStålemark Hvan’t Hooft IPrayer DGrois N: Incidence and pattern of radiological central nervous system Langerhans cell histiocytosis in children: a population based study. Pediatr Blood Cancer 56:2502572011


Nordmann TMJuengling FDRecher MBerger CTKalbermatten DWicki A: Trametinib after disease reactivation under dabrafenib in Erdheim-Chester disease with both BRAF and KRAS mutations. Blood 129:8798822017


Váradi ZBánusz RCsomor JKállay KVarga EKertész G: Effective BRAF inhibitor vemurafenib therapy in a 2-year-old patient with sequentially diagnosed Langerhans cell histiocytosis and Erdheim-Chester disease. OncoTargets Ther 10:5215262017




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