Intracranial Pathology of Erdheim Chester Disease

OBJECTIVE: To describe the intracranial pathology found in neurologic Erdheim Chester Disease (ECD). BACKGROUND: ECD is a rare non-Langerhans cell histiocytosis involving multiple organs including the CNS, where the presentation can resemble primary malignancy, lymphoma or inflammatory demyelination. Diagnosis requires finding CD68+, CD163+, CD1a-, CD207-, S100+/-, Factor XIIIa+ foamy macrophages. BRAF and other RAS genes mutations are associated with this disease. CNS histology is rarely or poorly described in the literature. DESIGN / METHODS: 5 patients with confirmed ECD (per consensus guidelines) who also had intracranial biopsies were evaluated under NHGRI study 11-HG-0207. Clinical, imaging and pathological evaluations were performed. RESULTS: Biopsies were from dura, temporal lobe, brainstem, pituitary and frontal lobe. One patient had the CD68+/CD1a- histiocytes in the temporal lobe with reactive lymphocyte infiltrates and demyelination. Another patient had inflammatory histiocytes in the brainstem. A third patient had had CD68+/CD1a+/S100+ histiocytes in the dura mater. A fourth patient had evidence of B-cell lymphoma (a known comorbidity in this patient) but no evidence of ECD in his brain. A fifth patient had a pituitary biopsy that was normal, in spite of having extensive pituitary involvement radiographically. Imaging and clinical findings varied amongst the 5 cases. CONCLUSIONS: The neurologic involvement of ECD is variable in patients with confirmed ECD. CNS histiocytes involved in the disease process can adopt cytopathological patterns atypical of ECD. Additionally, we saw neuropil invasion, demyelination, reactive lymphocytes and reactive glia. Overall, neurologic ECD exhibits CNS-specific features. These results may suggest an explanation for why neurologic involvement carries a poorer prognosis in ECD and raises the possibility that neuro-ECD may respond differently to treatments than systemic disease. Disclosure: Dr. Dave has nothing to disclose. Dr. Boyd has nothing to disclose. Dr. O9Brien has nothing to disclose. Dr. Gahl has nothing to disclose. Dr. Estrada-Veras has nothing to disclose.