MACROSCOPIC APPEARANCES

Hematogenous dissemination generally leads to multiple lesions, which vary from a few millimeters to several centimeters in diameter. These often occur in the anterior and middle cerebral artery distributions and involve the cerebral cortex (Fig. 17.1), white matter, and basal ganglia, but brain stem and cerebellar structures (Fig. 17.1) may also be affected.

Early lesions often resemble hemorrhagic infarcts (Fig. 17.1). These may form abscesses, although a thick fibrous capsule only rarely develops. In other lesions, there are foci of non-suppurative white or yellow necrotic material admixed with a variable amount of hemorrhagic tissue (Fig. 17.1). Much less frequently the fungus produces intraparenchymal granulomas or even meningitis. Aspergillus granulomas are usually a feature of chronic infection, but may be solitary lesions.

Aspergillus that enters the cranial cavity as a result of direct rather than hematogenous spread usually causes chronic, relatively localized infection with a tendency to fibrosis and granuloma formation.

MICROSCOPIC APPEARANCES

Prominent microscopic features are:

Hyphae are found in the lumen, the wall and adjacent tissue of blood vessels of varying caliber (Fig. 17.2) and may be visible as silhouette-like unstained structures in giant cells. Although they are faintly visible in hematoxylin and eosin preparations and stain with the PAS technique, the hyphae are most clearly demonstrated by methenamine silver impregnation. Because Aspergillus is morphologically similar to several other molds, a diagnosis of ‘invasive septate hyphae consistent with aspergillosis’ is the most accurate diagnosis that can be given on histopathology alone.

Neutrophils predominate in the early phase of disease and macrophages at later stages. In abscesses, frank pus can be seen in the center of the lesion and abundant neutrophil infiltration at the edges, in some cases accompanied by granulomas. Necrotizing non-suppurative lesions include zones of coagulative necrosis with scanty neutrophil reaction and hemorrhage. Both types of acute lesion are associated with vasculitis, vascular necrosis, and thrombosis (Fig. 17.3).

Granulomatous lesions consist of aggregates of lymphocytes, plasma cells, epithelioid macrophages, Langhans-type multinucleated giant cells, and variable amounts of collagen and necrotic tissue (Fig. 17.4). Chronic granulomas may become densely fibrotic.

Chronic abscesses may develop a dense collagenous connective tissue capsule (Fig. 17.5) without a granulomatous tissue reaction. The amount of inflammation varies from patient to patient and may be scanty in treated cases.

MACROSCOPIC APPEARANCES

In rhinocerebral mucormycosis, foci of hemorrhagic necrosis are most prominent in the orbital part of the frontal lobes (Fig. 17.6). Necrotic, hemorrhagic tissue is present in the nasopharynx, orbit, and adjacent skull base. There may be thrombosis in the cavernous sinus or carotid artery. When CNS involvement results from hematogenous dissemination, lesions tend to be concentrated in the basal ganglia.

MICROSCOPIC APPEARANCES

The diagnostic broad non-septate hyphae vary in caliber and branch at irregular intervals. They can be seen in and around the walls of blood vessels in the meninges and brain (Fig. 17.7). Admixed hyphae and thrombus occlude the lumina and are associated with extensive hemorrhagic infarction (Fig. 17.7). The hyphae, which may be relatively sparse, are best demonstrated by methenamine silver impregnation. A mixed or predominantly neutrophil inflammatory response may occur around the infiltrated blood vessels and where hyphae extend into adjacent brain tissue. Multinucleated giant cells are occasionally seen, but granulomas are not a typical feature.