Contributed by Yoo-Jin Kim, M.D. and Wolfgang Feiden, M.D.
Institute of Neuropathology, University of the Saarland, School of Medicine, Homburg/Saar, Germany
A 76-year-old woman operated on bladder cancer two months ago, presented with dysarthria and brachiofacial hypesthesia of the left side. Magnetic resonance imaging (MRI) revealed a T2-hyperintensity in the right gyrus precentralis with only minimal space-occupying effect (Figure 1). Application of Gadolinium revealed an inhomogeneous enhancement of this lesion (Figure 2). Magnetic resonance spectroscopy (MRS) suggested a metastasis, presumably, derived from to the bladder cancer. The patient underwent stereotactic biopsy.
Smear preparations at intraoperative consult revealed moderately cellular tissue with conspicuous astrocyte-like cells with radiating or plump processes (Figure 3). The blood vessels showed marked endothelial hyperplasia, sporadically with perivascular accentuated distribution of cells showing only slight cytological atypia and containing round, hyperchromatic nuclei (Figure 4). Strikingly, there were amounts of cells with large, glassy cytoplasm, containing multiple, small, and seemingly viable micronuclei of varying size ("mn" Figure 5, lower insets Figure 6) or chromatin clumps. Along with those cells, consistent with so called "Creutzfeldt cells", there were numerous granular mitoses with starburst-like appearance ("gm" Figure 5, central figure and upper insets, Figure 6). Some of these structures presented with individually distinguishable chromosomes ("c" upper right inset, Figure 6) or chromosomal fragments. Histopathologic examination of the formalin-fixed paraffin-embedded material of the small biopsy specimens revealed similar findings. The cellular elements were composed of atypical astrocytes with plump processes and hyperchromatic nuclei, small cells with indifferent and round nuclei, and a multitude of Creutzfeldt cells (the two large cells with multiple micronuclei in the centre and upper right inset of Figure 7). The micronuclei in the latter cells were often arranged peripherally and partially embedded in vesicles ("v" upper right inset in Figure 7). There were also mitotic figures (lower left inset, Figure 7) or large cells with chromosomal fragments (lower right inset, Figure 7). The tissue was dissociated and loosened, in one biopsy sample there was coagulative necrosis due to thrombosed blood vessels (right section, Figure 8). Majority of blood vessels showed marked endothelial proliferation (left section, Figure 8).
The cytoplasm of numerous cells, including the majority of the small cells with round nuclei as well as the plump processes of atypical astrocytes were marked with an antibody directed against glial fibrillary acidic protein (GFAP). The Creutzfeldt cells were also immunoreactive and presented a variable staining-intensity (insets, Figure 9). A relative decrease of axons and few axon bulbs were obvious in the neurofilament immunoreaction (Figure 10). Myelin stain (Luxol-fast-blue) showed a moderate loss of myelin. Ki-67 labeling showed an increased proliferative activity. Distinct labeling was also registered for the micronuclei of the Creutzfeldt cells (inset, Figure 11). Numerous nuclei showed an accumulation of p53 protein. Only few monocytes and macrophages (CD68) and sporadic T-lymphocytes (CD3) were detectable. No CD79 positive B-cells were verifiable.