Headache, Radicular Pain, and Enhancing Lesions

A 37-year-old right-handed woman sought care for a dull headache present for 6 months, which was followed by the development of radicular pain in the left leg radiating down the back of her leg into her foot, with associated left foot numbness. Magnetic resonance imaging of the lumbar spine showed an enhancing lesion within the conus. She was referred for neurosurgical evaluation and underwent magnetic resonance imaging of the entire neuraxis, which showed an enhancing lesion in the left cerebellum. She underwent a left cerebellar debulking surgical procedure. Postoperative diplopia developed for approximately 1 month and then subsequently resolved. She walked with a walker after surgery, with progressive deterioration in gait. Two months after surgery a postural tremor developed in the left arm and leg. She was referred for neurologic evaluation. Pathologic evaluation of cerebellar tissue showed foamy histiocytes and xanthomatous cells that stained positive for CD68 (KP1). Staining for CD1a was negative. Tissue immunohistochemistry for the BRAF V600E sequence variation was negative. No hyponatremia was detected. Positron emission tomography/computed tomography of the body from vertex to toes indicated hypermetabolism in the distal femur and proximal tibia. Examination and imaging findings were consistent with a diagnosis of multifocal Erdheim-Chester disease. The patient was initially treated with pegylated interferon, with clinical and radiographic progression. She was subsequently treated with vemurafenib and dexamethasone, with continued radiologic progression. Treatment with radiotherapy and cladribine were also unsuccessful. At that point, next-generation sequencing of cerebellar tissue showed a BRAF V471F sequence variation. She was then treated with trametinib, which resulted in a decrease in size of the cerebellar lesion and growth stabilization of the conus lesion. Histiocytic neoplasms are a heterogeneous group of multisystem disorders, primarily including Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease. Although initially thought to represent inflammatory processes, recent insights into their genomic architecture have shown that they are derived from macrophage-lineage neoplasms.