An 88-year-old woman with a history of diabetes mellitus, hypertension, hyperlipidemia, and coronary artery disease presented with right ptosis and binocular horizontal diplopia that had begun earlier that day. Examination was significant for anisocoria and a complete right third cranial nerve palsy. MRI brain revealed enhancement of the right oculomotor nerve as well as mass effect and edema in bilateral medial frontal lobes. Cerebrospinal fluid studies were remarkable for protein of 183 mg/dL, lymphocytic pleocytosis of 72 cells/cubic mm (84% lymphocytes), and flow cytometry showing a small population of variable-sized B lymphocytes with no definitive light chain expression, suggesting a B-cell lymphoproliferative disorder. Ultimately, leptomeningeal, pial, and parenchymal core biopsies were obtained from an enhancing lesion in left frontal lobe showing angiodestructive granulomatous mixed inflammatory infiltrate and exuberant reactive astrocytes, mostly T-cells and histiocytes, and a scant population of EBV-positive cells, consistent with the diagnosis of lymphomatoid granulomatosis (LYG).

This case highlights a rare etiology of a pupil-involving third nerve palsy. Despite MRI brain demonstrating enhancement of the third nerve initially and CSF suggesting lymphocytic pleocytosis, these were nonspecific findings and markers that are more specific were negative. Ultimately, a brain biopsy was necessary to confirm this EBV-driven lymphoproliferative disorder. The diagnosis of LYG may only be made by brain biopsy and may mimic disorders such as IgG4-related disease, metastatic disease and other granulomatous conditions.