Contributed by Patrick J. Cimino, MD, PhD and Richard J. Perrin, MD, PhD
Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
A 71 year old man presented with a two-day history of periodic severe left-sided occipital headache, blurry vision, alexia without agraphia, and occasional nausea without vomiting. His past medical history is significant for hypertension, for which he takes lisinopril, hydrochlorothiazide, and verapamil. He also takes meloxicam for arthritis and pantoprazole for gastroesophageal reflux. He has no personal history of malignancy, but does have a family history significant for esophageal cancer. He does not smoke or use alcohol or drugs, and has no known environmental exposures. Physical examination was remarkable only for a right visual field deficit. Magnetic resonance imaging (MRI) showed a 5.2 x 4.6 x 4.0 cm area of complex signal abnormality in the left occipital/posterior parietal region, with some cortical effacement and white matter edema, but no significant mass effect (T2-weighted MRI; Figure 1). All sequences showed serpiginous and punctate foci of low signal, suggestive of hypervascularity, but revealed no large feeding or draining vessels. There was no diffusion restriction. Irregular contrast enhancement involved a 4.3 x 3.8 x 3.2 cm region of the abnormality (T1-weighted post-gadolinium MRI; Figure 2). Computed tomography (CT) revealed an associated area of calcification near the sagittal sinus. For definitive diagnosis, a stereotactic left occipital brain biopsy was performed.
Hematoxylin and eosin stained sections of the FFPE biopsy specimen show abundant irregular lobules of acellular, pale eosinophilic material, variably separated by modest amounts of brain parenchyma with rare entrapped neurons and scattered atypical glial cells (Figure 3). Small vessels with thickened and hyalinized walls are numerous and, in some areas, merge into pale eosinophilic lobules. Several small patches with multinucleated giant cells, lymphocytes, plasma cells, and modest hemosiderin are present (Figures 4 and 5). Calcification and focal incipient ossification are present, but only in intraoperative frozen sections. A section stained histochemically with Congo Red and examined with polarized light microscopy reveals apple-green birefringence (Figure 6) within the pale eosinophilic deposits; on a section stained with thioflavin S and examined with fluorescence microscopy, the proteinaceous deposits fluoresce intensely (Figure 7). Immunohistochemistry (IHC) for endothelial marker CD34 highlights viable small caliber vessels within a subset of the proteinaceous deposits. Reactivity for glial fibrillary acidic protein (GFAP) highlights gliotic brain parenchyma between the deposits, in which reactivity for neurofilament protein (NF) reveals very sparse axons. IHC for lambda light chain shows very strong reactivity within the deposits (Figure 8), and to a lesser extent, within the brain parenchyma. In contrast, IHC for kappa light chain shows variable weak reactivity (Figure 9), and IHC for amyloid-beta peptide is non-reactive (Figure 10). The presence of abundant lambda light chain within microdissected Congo Red positive areas was subsequently confirmed by liquid chromatography tandem mass spectrometry (LC MS/MS). What is your diagnosis?