NQ-097 Answer: (A) Toxoplasma gondii

Diagnosis: Toxoplasmosis

Pathology of this case: There is a centrally located "ball with a granular skin" in the picture (arrow) or you can call it a ball of densely packed beads or seeds. Within this spherical structures are many small dark clumpy dots that correspond to bradyzoites. The diameter of this spherical lesion is around two to three times the diameter of the adjacent nuclei. These features are that of a cyst of toxoplasma. They are most frequently seen in the viable adjacent to the necrotic foci in toxoplasmosis. Very often, large, non-viable round eosinophilic, hyaline like featureless structure of the same size and shape are found within necrotic debris in toxoplasmosis. These structures are most likely dead cysts. They are suggestive but not diagnostic for toxoplasmosis. Viable cyst must be seen. Immunohistochemical staining is often helpful. it is because of the persistence of the cysts, demonstration of cysts in the absence of tissue reactions does not prove that an active infection is taking place. Bradyzoites are often difficult to be seen with HE stain (arrow) and are best demonstrated by immunohistochemistry.

Toxoplasma gondii is an intracellular parasite, remarkably, can invade and multiply inside most mammalian cell types nonselectively. It can circumvent the immune responses and allow it to survive indefinitely in the host. The definitive host is domestic cats. The sexual phase of the life cycle is in cats. Human acquires infection either by eating not thoroughly cook parasite infested meat or from contaminated feces of cat. Tachyzoites (cell-invasive proliferating form), and tissue cysts (containing bradyzoites, may contain up to 3000 bradyzoites each) are found in human tissue. A large number of people are infected worldwide but most of these cases are subclinical. Active infection can be resulted from primary infection and reactivation of a latent infection. Congenital infections can also occur. Many symptomatic cases occur in immunosuppressed host. Toxoplasmosis is one of the commonest opportunistic infection of the central nervous system (CNS) in patients infected by human immune deficient virus (HIV). The inflammatory change is often that of a granulomatous one with and without necrosis. The spectrum of pathology in the CNS  includes:

• Meningoencephalitis during primary infection in an immunocompetent host.
• Encephalitis and retinochoroiditis as a result of transplacental infection of the fetus.
• Retinochoroiditis associated with primary infection or reactivation of an earlier infection.
• Intracerebral mass lesions or encephalitis in immunocompromised hosts.
• Abscess formation in common in HIV infected patients.

    Immunohistochemistry is often a useful help in identification of Toxoplasma gondi.

[More information on the biology of Toxoplasma gondii]

Malarial encephalitis: Plasmodium falciparum is one of the several species of plasmodium that causes malaria and typically leads to severe clinical manifestations. Malarial encephalitis affects the CNS globally. Macroscopically, there are numerous globally distributed petechial hemorrhages. Microscopically, the small blood vessels and capillaries have swollen endothelial cells with extravasation of red blood cells. Dark pigmentation known as malarial pigment are common.There are also blockage of cerebral capillaries by erythrocytes with some of them may contain the parasite. Proteinaceous material may be seen around the involved vessels. There is necrosis of the perivascular white matter, focal loss of myelin staining, accumulation of reactive microglia and astrocytes in the vicinity.

Primary amoebic meningoencephalitis is caused by Naegleria fowleri, a fresh water amoeba that is found worldwide, and is almost uniformly fatal in 2 to 7 days. It usually occurs in healthy children and young adults, typically in summer or autumn. The parasite enters the CNS through the cribiform plate, often due to swimming in contaminated lakes or ponds. Macroscopically, it is a purulent meningitis with a relatively thin layer of exudates. Histologically, there is acute necrotizing and hemorrhagic meningoencephalitis with massive destruction of the brain. The trophozoites may appear as cells about 10-20 micron in diameter, with pale vesicular nuclei, and prominent nucleoli and are found in the Vichow- Robin or subarachnoid space; it is often difficult to distinguish them from macrophages. Viable organisms may be recovered. In fresh preparation or culture, the organisms show characteristic motility. In contrast to acanthoamoeba, they move swiftly.

Blastomycosis, also known as North American blastomycosis or Gilchrist’s disease, is found predominantly in North America and is endemic in the south-eastern regions of the United States including the Mississipi and also in Africa. Blastomyces dermatidis, the causative agent is found in soil and decayed wood. It may occur in an immune competent or compromised host. The route of entry is through the respiratory tract to the lung. Systemic dissemination to other organs including the brain can follow. It shares many clinical and pathological features of tuberculosis and, therefore, often mistaken clinically as tuberculosis. The incidence of CNS infection is only about 1.2% in patients with blastomycosis. Infection of the central nervous system can occur as meningitis, meningoencephalitis, and brain abscesses. Evidence of pulmonary disease is usually found in patients with CNS blastomycosis.  Meningitis is the most common form and typically occurs late in the course of disseminated disease; it may also be resulted from local extension. There is no reliable serologic test and CSF culture is rarely positive even in cases of B. dermatidis meningitis. An open biopsy to obtain tissue for culture is often necessary to establish the diagnosis. [Click here to see an image]