Inflammatory/Infectious Flashcards
Rasmussen encephalitis
For mysterious reasons, Rasmussen encephalitis (RE) always affects only one side of the brain. It is an inflammatory disease of the brain occurring most often in children (<15 yrs.). It is characterized by chronic inflammation involving one cerebral hemisphere and typically results in seizures, hemiparesis, and cognitive difficulties. While the underlying cause is unknown, the process is mediated by T cells, with neuronal loss, gliosis, and microglial activation of the affected region. The possibility of a viral infectious agent has been suspected for a long time but no such agent has ever been found. Antibodies against glutamate GluR3 receptors has have been associated with Rasmussen encephalitis but more recent studies show that these antibodies can be found in other epilepsy patients.
RE has an acute stage, where the inflammation is active and neuronal damage is occurring, followed by a chronic (residual) stage, where the inflammation has subsided but the damage remains. In some cases, a prodrome may be identified for a period of time prior to the onset of symptoms. Initially, the treatment involves managing the inflammation with steroids and possibly immunomodulation therapies. In the chronic stage, treatment is focused on improving symptoms. RE patients frequently experience seizures that are often refractory to medical management. Epilepsia partialis continua is a condition in which patients experience focal recurrent motor epileptic seizures, and may be seen in patients with RE. When seizure activity is persistent and/or refractory to medical management, a hemispherectomy (surgical removal of affected hemisphere) may be performed to remove the source of the seizures.
Coccidioides immitis
Coccidioides is the large, ranging from 10 to 80 μm in size, and contains numbers spherules with thick, refractile wall. Like other fungal organisms, they are well demonstrated by GMS and PAS stain, but is also one of the few fungal organisms that can be recognized with hematoxylin and eosin stain.
Coccidioides immitis fungus is native to the San Joaquin Valley of California. Together with Coccidioides posadasii which is endemic to certain arid-to-semiarid areas of the southwestern United States they are the two most commonly seen organisms that cause coccidioidomycosis in the United States. Coccidioidomycosis is usually transmitted by inhalation of airborne spores. Coccidioidomycosis is not associated with compromised immunity.
Histoplasma, Coccidioides, and Blastomyces are often due to systemic dissemination and not associated with compromised immunity. Cryptococcus and Toxoplasma, in contrast, do not cause major problem in most healthy patients but can be serious conditions for immune compromised patients such as HIV(+) patients.
Cryptococcus neoformans
Cryptococcus is a medium sized yeast that is not stained and appears as a negative image among the cytoplasm stained by the Diff-Quick. One should note that the yeast appears as small bright dots on low magnification which can be easily dismissed as entrapped air bubbles. On hematoxylin and eosin stain, Cryptococcus often appears as perfectly round transparent discs that do not take up stain. But their presence is best demonstrated by the use of special stains such as PAS and GMS. In particular, the mucopolysaccharide outer coat of Cryptococcus is positive for mucicarmine stain.
Cryptococcus infection of the brain typically manifests as meningitis. It is relatively uncommon to manifests as meningoencephalitis. In contrast to Naegleria fowleri, most cryptococcal yeast tend to occur as dead fungal organisms that are almost transparent that fail to pick up significant staining on HE stained sections. They like to grow in the Vichow-Robin space and expand them. A PAS, mucicarmine, or GMS stain can highlight these organisms very well.
Prion disease
The pathologic changes here are characterized by diffuse spongiotic changes in the cortex but not in the white matter. The spongiotic changes can be differentiated from fixation artifact because the white matter is not very much affected in comparison to the cortex.
The other histologic features being shown here is almost total loss of neurons. There is extensive gliosis with spongiotic changes in the cortex. Cytoplasmic vacuoles are seen in the neuornal bodies (arrows). The latest is a strong suggestion of prion associated spongiotic encephalopathy. The diagnosis, however, must be confirmed by immunohistochemistry and biochemical studies.
Spongiotic encephalopathy
seen in multiple conditions including spongiotic form encephalopathy (prion diseases), poisoning and and intoxication such as methanol intoxication, metabolic diseases such as Canavan’s disease and amino acid metabolic diseases, and others.
Blastomycosis
Broad based budding yeast. most commonly seen as a primary lung infection and also as skin infection but some of them may disseminate and involve other parts of the body including the central nervous system. The clinical symptoms are similar to histoplasmosis. It is not associated with compromised immunity. Blastomycosis or North American blastomycosis are endemic in eastern North America particularly in the western and northern periphery of the Great Lake Basin with extension along the St. Lawrence River valley into the central Appalachian Mountains and to Mississippi.
Candida
Small yeast without broad based budding
Histoplasmosis
Appears as numerous small dots on hematoxylin that can be easily seen on hematoxylin and eosin stained sections. On PAS, histoplasma is strongly positive an typically have a centrally located dots.
Naegleria fowleri
A fresh water ameba that appears as mononuclear, round to oval cells with dense and hyperchromatic round nuclei. The cytoplasm is amphophilic and sometime vacuolated. Can easily be mistaken as macrophages. Genuine macrophages, however, can also be seen in these cases in necrotic areas. Causes a meningoencephalitis that is typically fatal. Amoeba are most easily found in perivascular spaces with a low to medium amount of cellular infiltration and in areas relatively free from necrosis. The background inflammation is often a mixture of polymorphonuclear leukocytes and lymphocytes.
Toxoplasma gondii
Toxoplasmosis in the brain typically manifests as an intra-parenchymal mass that may simulate a brain tumor. Meningitis and meningoencephalitis is not the usual presentation.
Plasmodium falciparum
Gross pathology of the brain involved by malaria is characterized by numerous petechiae and they are most easily seen on cross sections. The histopathologic highlights are mostly in the mostly the small vessels and capillaries characterized by swollen endothelial cells with extravasation of red cells. Blockage of cerebral capillaries by erythrocytes, some may contain the parasite. Malarial pigment can also be seen in the capillaries Proteinaceous material may be seen around the involved vessels. There is necrosis of the perivascular white matter, and focal loss of myelin staining, also accumulation of reactive microglia and astrocytes in the vicinity.
Post mortem bacterial growth
Due to post mortem growth of gas producing bacteria, also known as “Swiss cheese brain”. Clostridium species are most commonly involved but not always the case. These changes will be more pronounced in obese patient and in dead body that has been stored in higher than optimal temperature.
Lymphocytic hypophysitis
lymphocytic hypophysitis may produce a sellar mass. Sections and cytologic smears would contain lymphocytes. There should not be large atypical cells. Due to the presence of some fibrosis in lymphocytic hypophysitis, the specimen usually would not smear out well.
Non-perfusion brain
aka ventilator brain. The increase in intracranial pressure in these brain exceeds the mean systemic systolic blood pressure and no blood is able to circulate into the brain. As a result, the brain undergo necrosis. It is basically acute infarction of the entire brain. However, because there are no neutrophils and histiocytes to break down the tissue due to the blockage of blood supply, the overall tissue morphology can be preserved even the patient has been maintained on ventilator for a few days. Cells in the central nervous system undergo necrosis in different speed. In the earlier stage of non-perfusion brain, some glial cells that could still be stained by hematoxylin would still be present. Sections will demonstrate many ghost shadows of triangular shaped cells consistent with neurons and the overall pattern of distribution consistent with that of the cerebral cortex with mild disintegration of the histologic details, vacuolation around the neurons, loss of cytologic details, and no nuclei.
Tissue samples that are over decalcified with acid based decalcification solution often lead to failure of hematoxylin staining. What differentiate overdecal from non-perfusion brain is that over decalcified sections have poor hematoxylin staining but the nuclear details are preserved.
Vitamin B12 deficiency/ Friedreich’s ataxia
Rarefied, pale staining and poorly demarcated areas in both the lateral column and dorsal column. On luxol fast blue-cresyl violet stain, there is loss of myelin in the corresponding area. Loss of myelination and degeneration of posterior column and dorsal column are features shared by subacute combined (i.e., dorsal and lateral column) degeneration due to vitamin B12 deficiency and Friedrich ataxia. Diagnosis of these two entities rely more on biochemical and genetic studies. The spinal cord has very little way to manifest pathologic changes.
