Cryptococcal organisms can be visualized within the brain parenchyma of both intraoperative and fixed tissues. (A) Intraoperative touch preparation/smear depicting classic “soap bubble” lesions comprised of yeast cells within clear gelatinous capsules infiltrating the brain parenchyma. An absence of inflammatory cells was noted; the lack of an appreciable inflammatory response is characteristic of many cryptococcal infections. The scale bar represents 100 μm. (B) An intraoperative frozen section demonstrated spherical-to-oval, variably sized, encapsulated yeast cells. The organisms were refractile, and many had circumferential halos. The scale bar represents 100 μm. (C) Low-magnification image of periodic acid-Schiff (PAS) staining showing infiltration of brain parenchyma by positively staining yeast cells, morphologically consistent with Cryptococcus. The scale bar represents 200 μm. (D) Higher magnification of the image in panel C highlighting the refractile appearance and the intensely stained mucopolysaccharide capsule of the yeast forms in tissue sections. Of note, mucicarmine and alcian blue also showed positive staining in the capsule of cryptococcal organisms (not shown). The scale bar represents 100 μm. (E) Low-magnification image of Grocott-Gomori’s methenamine silver (GMS) staining showing a representative field with innumerable yeast cells, some with narrow-based budding. The scale bar represents 500 μm. (F) Higher magnification of the image in panel E illustrating the intense staining of organisms within the brain parenchyma (stained light green by the counterstain). The scale bar represents 100 μm.