Erdheim-Chester Disease Masquerading as CLIPPERS

Area of Science:

• Neurology
• Oncology
• Radiology
• Histopathology

Background:

• Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by multiorgan infiltration of clonal histiocytes.
• Neurologic involvement occurs in up to 40% of ECD cases, frequently presenting with brainstem lesions.
• These brainstem lesions can mimic acquired neuroinflammatory disorders, notably chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

Purpose of the Study:

• To present four patients with Erdheim-Chester disease (ECD) exhibiting enhancing brainstem lesions.
• To differentiate ECD from CLIPPERS based on clinical, radiologic, histopathologic, and molecular genetic findings.
• To emphasize the importance of considering ECD in the differential diagnosis of CLIPPERS mimics.

Main Methods:

• Retrospective case series analysis of four patients with Erdheim-Chester disease.
• Evaluation of clinical presentations, neuroimaging (MRI, PET-CT), histopathology, and molecular genetic data.
• Comparison of findings with established criteria for CLIPPERS.

Main Results:

• Patients with ECD presented with enhancing brainstem lesions, initially suspected as CLIPPERS.
• Key differentiating features included refractoriness to corticosteroids, atypical MRI characteristics (lesion size, T2/T1 enhancement mismatch), and systemic findings (e.g., 'hairy kidney,' osteosclerosis).
• Molecular genetic analysis revealed activating MAPK-ERK pathway variants in ECD histiocytes.

Conclusions:

• Erdheim-Chester disease is an important mimic of CLIPPERS, with distinct pathophysiology and targeted treatment options.
• Systemic manifestations and specific imaging criteria are crucial for differentiating ECD from CLIPPERS.
• Histiocytic disorders, including ECD, should be considered in the differential diagnosis when neuroinflammatory findings are not classic for CLIPPERS.