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Progressive Neurological Impairment and an Enhancing Brainstem Lesion in a Middle-aged Man

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 53-year-old man developed patchy numbness in his right arm. The numbness progressed over 10 months to involve his entire right arm, patches of his left arm, and his distal lower extremities. He also developed right-hand incoordination and imbalance. A magnetic resonance image (MRI) of the brain is shown in Figure 1A. A complete blood cell count with a differential; liver function testing; tests for HIV, rapid plasma reagin, serum aquaporin-4 antibody, and antinuclear antibodies; and levels of sodium, calcium, creatinine, glucose, thyroxine, and vitamin B12 were unremarkable. Examinations of the cerebrospinal fluid had normal results twice, including for white blood cell count with a differential, glucose level, total protein level, IgG index, oligoclonal bands, cultures, and cytology testing.

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B. Erdheim-Chester disease

A skeletal survey radiographic series revealed sclerosis of the bilateral proximal tibias. A tibial bone biopsy by interventional radiology showed replacement of the marrow with fibrous stroma and bland, fibroblast-like spindle cells. Further biopsy testing included hematoxylin-eosin staining with foamy histiocytes and testing for cluster of differentiation 68 protein to confirm histiocyte presence. Tests for S100 and cluster of differentiation 1a proteins had negative results. Together, these findings supported the diagnosis of Erdheim-Chester disease (ECD), a rare, non-Langerhans cell–associated histiocytic disorder.

Neurosarcoidosis can also cause persistently enhancing parenchymal mass lesions, pachymeningitis, and optic neuritis, but these types of infiltrative soft-tissue and osteosclerotic lesions are atypical. Osteosclerotic lesions are also atypical for diffuse large B-cell lymphoma, and the relative MRI stability of the brain lesions over time is less consistent (particularly without exposure to glucocorticoids). Anti–myelin oligodendrocyte glycoprotein (MOG) antibody can cause an acute disseminated encephalomyelitis phenotype, but anti-MOG disease would not account for extranervous system pathology, and the pattern of persistent nodular enhancement and pachymeningeal involvement are not consistent. The pathology of ECD is also distinct; this case highlights the importance of clinical correlation, systemic evaluation, and pathological confirmation.

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Article Information

Corresponding Author: Jeffrey M. Gelfand, MD, MAS, Department of Neurology, University of California, San Francisco, 1500 Owens St, Ste 320, PO Box 3206, San Francisco, CA 94158 (jeffrey.gelfand@ucsf.edu).

Published Online: September 16, 2019. doi:10.1001/jamaneurol.2019.3002

Conflict of Interest Disclosures: Dr Gelfand reports consulting fees from Biogen and Alexion; research support (to University of California, San Francisco [UCSF]) from Genentech; service contracts (to UCSF) from MedDay; honoraria for editorial work from Dynamed Plus; personal compensation for medicolegal consulting from Alkem Laboratories Ltd, Accord Healthcare Inc, Apotex Corp, Apotex Inc, Teva Pharmaceuticals USA Inc, Roxane Laboratories Inc, Mylan Pharmaceuticals Inc, and Merck; and fees as an expert from the Vaccine Injury Compensation Program. His spouse has received consulting fees from Theranica, Impel Neuropharma, Eli Lilly, Impax and Zosano; grants from Amgen; and honoraria from UpToDate (for authorship) and JAMA Neurology (as an associate editor). eNeura pays consulting fees for his spouse’s work to the UCSF Pediatric Headache program; his spouse receives personal fees for medicolegal consulting.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Cavalli  G, Guglielmi  B, Berti  A, Campochiaro  C, Sabbadini  MG, Dagna  L.  The multifaceted clinical presentations and manifestations of Erdheim-Chester disease.  Ann Rheum Dis. 2013;72(10):1691-1695. doi:10.1136/annrheumdis-2012-202542PubMedGoogle ScholarCrossref
2.
Diamond  EL, Dagna  L, Hyman  DM,  et al.  Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease.  Blood. 2014;124(4):483-492. doi:10.1182/blood-2014-03-561381PubMedGoogle ScholarCrossref
3.
De Filippo  M, Ingegnoli  A, Carloni  A,  et al.  Erdheim-Chester disease.  Radiol Med. 2009;114(8):1319-1329. doi:10.1007/s11547-009-0473-8PubMedGoogle ScholarCrossref
4.
Diamond  EL, Subbiah  V, Lockhart  AC,  et al.  Vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis.  JAMA Oncol. 2018;4(3):384-388. doi:10.1001/jamaoncol.2017.5029PubMedGoogle ScholarCrossref
5.
Ozkaya  N, Rosenblum  MK, Durham  BH,  et al.  The histopathology of Erdheim-Chester disease.  Mod Pathol. 2018;31(4):581-597. doi:10.1038/modpathol.2017.160PubMedGoogle ScholarCrossref
6.
Diamond  EL, Durham  BH, Ulaner  GA,  et al.  Efficacy of MEK inhibition in patients with histiocytic neoplasms.  Nature. 2019;567(7749):521-524. doi:10.1038/s41586-019-1012-yPubMedGoogle ScholarCrossref
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