Not Right in the Head' - Video

The patient underwent biopsy of the left orbital lesion. Histopathologic examination showed chronic sclerosing orbititis with perivasculitis, focal occlusive vasculitis, xanthogranulomatous inflammation, and fat necrosis. Staining was negative for microbes, and flow cytometry demonstrated no lymphoproliferative disorder. The IgG4+/IgG+ plasma cell ratio was 12%. He was referred to a rheumatologist for further work-up. Quantiferon gold, ACE, SPEP, C3, C4, IgG, IgG4, RF, hepatitis B and C serologies, and antibodies to ds DNA, SSA, SSB, CCP, myeloperoxidase, and proteinase-3 were all unremarkable. He was treated with prednisone for non-specific orbital inflammation. Symptoms improved on 60 mg/day, but worsened on tapering below 30 mg/day. He was then started on methotrexate. However, vision in the left eye decreased to 20/200 and a left APD developed. He was switched to cyclophosphamide for possible ANCA-negative granulomatous polyangiitis. One month later, his family brought him to the ED because he was "not right in the head." Vision decreased to 20/25 OD and was stable at 20/200 OS. MRI brain and orbits showed enhancement of the intraconal fat bilaterally. Additionally, there were multiple foci of abnormal T2 hyperintense signal within the brainstem, cerebellum, and deep nuclei of the cerebrum. The pituitary gland was enlarged and enhanced heterogeneously. These findings were interpreted by neuroradiologists as consistent with lymphoma, and less likely sarcoid, granulomatous polyangiitis, nonspecific orbital inflammation, or Erdheim-Chester disease. A radionuclide bone scan showed significantly increased radiotracer activity throughout the lower extremities. The original biopsy specimen then underwent further immunohistochemistry, which was negative for anti-CD1a, strongly reactive for anti-CD 68, and partially reactive for anti-S100. BRAF V600E mutation analysis was positive. Based on radiologic and histopathologic findings, the patient was diagnosed with Erdheim-Chester disease.