Neurologic and oncologic features of Erdheim–Chester disease: a 30-patient series. Issue 7 (17th January 2020)

• Record Type: Journal Article
• Authors: Bhatia, Ankush; Hatzoglou, Vaios; Ulaner, Gary; Rampal, Raajit; Hyman, David M; Abdel-Wahab, Omar; Durham, Benjamin H; Dogan, Ahmet; Ozkaya, Neval; Yabe, Mariko; Petrova-Drus, Kseniya; Panageas, Katherine S; Reiner, Anne; Rosenblum, Marc; Diamond, Eli L
• Is Part Of: Neuro-oncology. Volume 22:Issue 7(2020)
• Page Start: 979
• Page End: 992
• Publication Date: 2020-01-17
• Subjects: central nervous system -- Erdheim–Chester disease -- histiocytosis -- MAPK pathway -- targeted therapy; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa008
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Erdheim–Chester disease (ECD) is a rare histiocytic neoplasm characterized by recurrent alterations in the MAPK (mitogen-activating protein kinase) pathway. The existing literature about the neuro-oncological spectrum of ECD is limited. Methods: We present retrospective clinical, radiographic, pathologic, molecular, and treatment data from 30 patients with ECD neurohistiocytic involvement treated at a tertiary center. Results: Median age was 52 years (range, 7–77), and 20 (67%) patients were male. Presenting symptoms included ataxia in 19 patients (63%), dysarthria in 14 (47%), diabetes insipidus in 12 (40%), cognitive impairment in 10 (33%), and bulbar affect in 9 (30%). Neurosurgical biopsy specimens in 8 patients demonstrated varied morphologic findings often uncharacteristic of typical ECD lesions. Molecular analysis revealed mutations in BRAF (18 patients), MAP2K1 (5), RAS isoforms (2), and 2 fusions involving BRAF and ALK . Conventional therapies (corticosteroids, immunosuppressants, interferon-alpha [IFN-α], cytotoxic chemotherapy) led to partial radiographic response in 8/40 patients (20%) by MRI with no complete responses, partial metabolic response in 4/16 (25%), and complete metabolic response in 1/16 (6%) by 18 F-fluorodeoxyglucose (FDG)-PET scan. In comparison, targeted (kinase inhibitor) therapies yielded partial radiographic response in 10/27 (37%) and complete radiographic response in 14/27 (52%) by MRI, and partial metabolic response in 6/25 (24%) and complete metabolic response in 17/25 (68%) by FDG-PET scan. Conclusions: These data highlight underrecognized symptomatology, heterogeneous neuropathology, and robust responses to targeted therapies across the mutational spectrum in ECD patients with neurological involvement, particularly when conventional therapies have failed.