MACROSCOPIC APPEARANCES

The cerebral lesion is usually single and located in the cortical gray matter, basal ganglia, or at the junction between cortex and white matter. Early lesions appear as small foci of hemorrhagic softening. These become necrotic, with yellow–green centers, and later cavitate. The walls are irregular and there is no evidence of encapsulation. Occasionally there are multiple abscesses.

MICROSCOPIC APPEARANCES

Cerebral amebic abscesses contain inflamed necrotic tissue and it may be difficult to distinguish E. histolytica trophozoites within this tissue from macrophages. The trophozoites are spherical or oval, 15–25 μm in diameter, and have vacuolated cytoplasm and a single nucleus. Occasionally pseudopodia can be seen. In routinely stained sections, the nuclei are round and have a small central karyosome and peripheral chromatin (Fig. 18.1). The cytoplasm contains abundant glycogen.

Trophozoites can usually be identified in the abscess wall, which has an inner zone of necrotic tissue and a broad outer zone with prominent congestion and vascular proliferation. Reactive gliosis and an infiltrate of lymphocytes, plasma cells, macrophages, and some neutrophils are seen in the surrounding brain.

MACROSCOPIC APPEARANCES

The brain is swollen and there is a hemorrhagic exudate in the meninges over the cerebrum, brain stem, and cerebellum. The olfactory bulbs and tracts and the adjacent parts of the frontal and temporal lobes contain areas of hemorrhagic necrosis (Fig. 18.2).

MICROSCOPIC APPEARANCES

A scanty mononuclear inflammatory infiltrate (Fig. 18.2) with focal hemorrhage is seen in the meninges, and there is usually extensive necrosis of brain parenchyma. N. fowleri amebae are present in the subarachnoid space and around vessels in the necrotic parenchyma (Fig. 18.3). Their diameter, of 8–15 μm, is slightly less than that of E. histolytica. They resemble macrophages, but can be distinguished from them by their vesicular nucleus with its large central nucleolus.

MACROSCOPIC APPEARANCES

The brain is usually swollen, covered by a diffuse leptomeningeal exudate, and includes foci of softening, hemorrhage, and necrosis, particularly in the anterior part of the cerebral hemispheres, the thalamus (Fig. 18.4), brain stem, and cerebellum (Fig. 18.5).

MICROSCOPIC APPEARANCES

The brain shows foci of chronic inflammation centered around arteries and veins. The inflammation is typically granulomatous and includes lymphocytes, macrophages, plasma cells, and multinucleated giant cells, but may be necrotizing. There is also a chronic inflammatory infiltrate in the meninges (Fig. 18.6). Acanthamoeba or Balamuthia trophozoites and cysts may be found in and around the walls of affected blood vessels (Fig. 18.6), and also in areas relatively free of inflammation (Fig. 18.6). The amebae are 15–40 μm in diameter and have a prominent vesicular nucleus with a dense central nucleolus. The cysts are surrounded by a double membrane (Fig. 18.6).

MACROSCOPIC APPEARANCES

The brain is usually swollen with congested leptomeninges. The cerebral cortex may appear dusky pink color due to marked congestion, or slate gray due to the presence of abundant malarial pigment (Fig. 18.8). The white matter often contains petechial hemorrhages.

MICROSCOPIC APPEARANCES

The small vessels are engorged by red blood cells, which may have a ghost-like appearance with poor staining of hemoglobin (Fig. 18.9). Many of these cells, particularly in the gray matter, contain malaria parasites and/or granules of dark malarial pigment, which is related to hematin. Marginated aggregates of red blood cells may appear to be adherent to the vascular endothelium (Fig. 18.10).

Edema, capillary necrosis, and perivascular hemorrhages are usually evident, and there may be parenchymal and meningeal infiltration by lymphocytes and macrophages. Petechial or larger hemorrhages can occur in any part of the brain, but are most common in the white matter and may surround necrotic arterioles and veins (Fig. 18.11). Patients with longer survival may harbor foci of softening and gliosis. Collections of microglia and astrocytes, the so-called Dürck granulomas, are probably related to resorption of ring hemorrhages (Fig. 18.11). The microglia contain iron pigment and lipid.

MACROSCOPIC APPEARANCES

The brain typically contains multifocal necrotic lesions of variable size (Fig. 18.12). There may be associated hemorrhage. Older lesions are cystic due to resorption of necrotic material. The basal ganglia are often involved, but any part of the brain may be affected. Occasionally brain involvement results in an encephalitic process without obvious focal lesions on macroscopic examination.

MICROSCOPIC APPEARANCES

Necrotizing abscesses or foci of coagulative necrosis are surrounded by mononuclear and polymorphonuclear inflammatory cells, newly formed capillaries, reactive astrocytes, and microglia (Fig. 18.13). Infiltrates of lymphocytes and macrophages surround the blood vessels. Scanty fibrous encapsulation may be evident. Other findings include intimal proliferation and thrombosis, fibrinoid necrosis (Fig. 18.13), and perivascular hemorrhage. The pathological findings depend partly on the degree of impairment of immune function: inflammation is less prominent and fibrosis usually absent in patients whose immune function is severely compromised.

Intracellular and extracellular Toxoplasma tachyzoites (also known as endozoites or trophozoites) are usually abundant. They are oval- or crescent-shaped and measure 2–4 μm by 4–8 μm (Fig. 18.14). Those within cells may be clustered together (in vacuoles or larger pseudocysts) or may appear to lie free in the cell cytoplasm. They can be seen reasonably well when stained with hematoxylin and eosin, but are more readily identified and distinguished from other protozoa immunohistochemically (Fig. 18.15). Cysts measuring 20–100 μm in diameter and containing large numbers of bradyzoites (also known as cystozoites) may occur within, or at the periphery of, the necrotic areas (Figs 18.15, 18.16).

Chronic lesions consist of cystic spaces containing macrophages and only very rare tachyzoites. Cerebral toxoplasmosis occasionally causes a diffuse non-necrotizing inflammatory process with scattered microglial nodules and astrocytic gliosis involving both gray and white matter. In HIV patients who have received cART, end-stage (burnt out) lesions are common: foci of cavitation and gliosis without a surrounding tissue reaction. However, in patients who develop IRIS, there may be florid inflammation.

MACROSCOPIC APPEARANCES