CNS Pathology Flashcards
Clinical involvement by CNS toxoplasmosis is seen in immunocompromised individuals, most notably in HIV+ patients, and involves usually cerebral cortex and deep gray matter nuclei. The infection reflects reemergence of latent disease acquired previously as a result of ingestion of infected food. The latent form is represented by slow-growing protozoa forms called bradyzoites encased in cysts with a cyst wall (arrows). Multiple basophilic dot-like parasites can be seen in cysts. A primary CNS infection may go unnoticed with this latent form and may never produce clinical symptoms
Active CNS disease is characterized by the presence of tachyzoites, which are free parasites in the tissue and which incite an inflammatory response. The cause of transformation of bradyzoite forms to tachyzoites during immunosuppression is not completely known. Tachyzoites are crescent-shaped 4-8 microns big organisms with a nucleus (arrow) that freely invade into the neuropil. This results in a mixed inflammatory reaction that may form large abscesses with ensuing focal CNS symptoms.
Clinical CNS involvement may be heralded by focal neurologic symptoms or non-specific symptoms such as fever, headache, and confusion. Brain MRI typically shows ring-enhancing lesions, which is characteristic but not diagnosis of this infection as similar lesions are seen in primary CNS large B-cell lymphoma, CNS tuberculosis, and CNS fungal infections. Toxoplasma cyst (arrow) shows a true cyst wall but may be mistaken for necrotic cell debris if not actively searched for. In active disease inflammatory cells may surround the cysts.
What’s on the differential for ring-enhancing CNS lesions?
The differential diagnosis of ring-enhancing CNS lesions with mass effect includes pyogenic brain abscess, syphilitic gummas, toxoplasmosis, TB, fungal infection, neurocysticercosis, gliomas, and lymphomas.
Arachnoidal cells in Arachnoid villi
Arachnoid granulations (dura peeled back)
Arachnoid, pia, subarachnoid space
Arachnoid villi
Aspergillus Hyphae in Blood vessels
Basal exudate - H. Influenzae (left)
Sonvexity exudate - S. Pneumoniae
What is the brown stuff?
Brown is normal lipofuschin due to aging
Cryptococcus neoformans (soap bubble appearance)
Cryptococcus neoformans (soap bubble appearance)
Cryptococcus neoformans (soap bubble appearance)
Cysticercosis
Cysticercosis
What is the organism?
How is it transmitted?
Cysticercosis
Taenia solium - larvae in pigs!
Cytoplasmic round Lewy inclusion
Is this early or late in abscess formation?
Early abscess
What are the labeled cells?
O - oligodendrocytes
N - neurons
A - astrocytes
Gray or white matter?
Gray matter - there is a neuron cell body, and the oligodendrocytes are surroundeing the cell body
Grocott silver stain - Aspergillosis
Herpetic encephalitis - temporal lobes affected
What type of virus?
HIV encephalitis - multinucleated giant cells
Intranuclear CMV inclusion
Example of intranuclear inclusion - viral encephalitis
Progressive multifocal leukopathy (JC polyoma virus)
Progressive multifocal leukopathy (JC polyoma virus)
Is this early or late in abscess formation?
Late
Microglia
Microglial nodule - one of the features of acute viral encephalitis
Microglial nodule - one of the features of acute viral encephalitis
Which two features of acute viral encephalitis does this picture illustrate?
Microglial nodule and neurophagia - two of the features of acute viral encephalitis
Microglial nodule and neuronophagia - two of the features of acute viral encephalitis
Mucormycosis / Zygomycosis
Mucormycosis/Zygomycosis
Mucormycosis/Zygomycosis
Mucormycosis/Zygomycosis
What disease are these associated with?
Rabies
Negri bodies
Negri bodies
Negri bodies
Neurofibrillary tangle
Neuromelanin in the substantia nigra, normal
Where is the Nissl substance?
In the dendrite but not in the axon
Neuronophagia - one of the features of viral encephalitis
Which of the brains is normal? Why is the other brain opaque?
Left is normal. The other brain is aged - collagen is deposited in the subarachnoid space, making it opacified
Features of the oligodendrocyte?
Lots of Golgi - it needs to make lots of membranes. Smaller than neuron.
Perivascular inflammatory infiltrate - a feature of viral encephalitis
Perivascular inflammatory infiltrate - a feature of viral encephalitis
Perivascular inflammatory infiltrate - a feature of viral encephalitis
Rabies
Are these neurons normal?
Nope, they’re red neurons - eosinophilic, possibly due to ischemia. These are neurons of Ca1
Red neuron of the cerebellum (Purkinje)
Which side is normal?
Right
TB, acid-fast stain
TB, giant cells around necrotic center
Tuberculosis meningitis, basal brain
Toxoplasmosis
Toxoplasmosis
Do these cysts resemble an expansile (growing) or necrotizing (destructing) pathology?
The smooth walls and uniform shapes of the cysts suggest a predominantly expansile process rather than a predominantly necrotizing process. (Cryptococcus)
What is this organism? What kind of stain?
Cryptoccocus - India Ink
Mucicarmine stain = red
What is mucicarmine?
How does it relate to the stained organism?
Mucicarmine stain (mucicarmine stains mucin red) reveals that the organisms filling the expanded spaces produce abundant mucoid material, a characteristic of cryptococcus. This explains the “glistening” nature of these areas seen when viewing the gross specimens
Which pathogen most likely caused these inclusions in this AIDS patient? How else might they present?
Cytomegalovirus (CMV) is the most likely cause. CMV causes both intranuclear and intracytoplasmic inclusions. The typical CMV intranuclear inclusions are brightly eosinophilic and are sometimes compared to an “owl’s eye”.
Cryptococcus
Cryptococcus in VR space
Was this abscess likely the cause of the patient’s death? How can you tell?
Not the cause of death. The border of the abscess has successfully healed, suggesting that it was drained prior to the patient’s death. Also, there is no significant mass effect on the lateral ventricle, also favoring the hypothesis that this was not the cause of death.
Bacterial Meningitis, Microscopic (H&E)
Bacterial meningitis, H&E stain, microscopic view. The subarachnoid space is packed with acute inflammatory cells (polymorphonuclear leukocytes). The bacteria are present but not visible at this magnification
Tuberculous Meningitis
The basilar leptomeninges are opacified by chronic inflammation. The brainstem, cerebellum, and cranial nerves are obscured. This is a typical example of chronic meningitis, which tends to be relatively localized to the basilar meninges
Herpes Encephalitis
This brain was removed at autopsy from a patient who suffered from Herpes encephalitis two years prior to death. The left temporal lobe is selectively and severely affected. Much of the lobe is missing, yet the remainder of the brain appears relatively intact. Herpes encephalitis is an aggressively necrotic disease. The dead brain tissue has been largely phagocytosed and removed, leaving a large defect with relatively smooth edges.
Tan-brown discoloration of the anterior horns due to poliomyelitis
H and E stained classical Lewy body in the substantia nigra characteristic of Parkinson’s disease. The Lewy body has a central eosinophilic core surrounded by a pale halo. Note the displacement of the neuromelanin to the periphery of the cell.
Pigmented neuron with multiple Lewy bodies stained with an antibody specific for alpha-synuclein, the main component of these inclusions.
Globose tangles and neuropil threads characteristic of progressive supranuclear palsy stained with an antibody for tau (which makes it look brown).
Cerebral Atrophy, Hippocampus
Coronal section of formalin fixed brain at the level of the lateral geniculate nucleus. There is prominent atrophy of the hippocampus bilaterally, as well as marked dilatation of the lateral ventricles.
Glial cytoplasmic inclusions in the midbrain characteristic of multiple system atrophy stained with an antibody to alpha-synuclein, that makes it look brown. In contrast to Parkinson’s disease, these alpha-synuclein inclusions are predominantly within oligodendrocytes.
Alzheimer’s Disease, Limbic Neuronal Loss and Senile Plaques
H&E stained section of hippocampus. There is neuron loss with associated gliosis (increased numbers of glial cells) and many senile plaques (circles), seen on H&E as bright eosinophilic deposits of amorphous extracellular material.
Right lateral view of brain from a patient with a clinical diagnosis of frontotemporal dementia (FTD) showing prominent frontal lobe atrophy. The parietal and occipital lobes are relatively spared.
Pick bodies in the dentate gyrus of patient with frontotemporal dementia. These inclusions are composed of the microtubule-associated protein tau similar to the neurofibrillary tangles of Alzheimer’s disease.
Immunohistochemistry for TDP-43
Examples of different types of inclusions in ALS: Filamentous (skein like) and round intracytoplasmic neuronal inclusions in anterior horn cells of the spinal cord and in the substantia nigra (bottom right).
Alzheimer’s Disease, Senile Plaques and Neurofibrillary Tangles
Thioflavin S stain of neocortex demonstrating senile plaques, neurofibrillary tangles, and neuropil threads. These are characteristic features of Alzheimer’s disease. (Thioflavin S is a fluorescent dye that specifically binds crossed, b-pleated sheet amyloid structures, characteristics of these inclusions in the AD brain.)
Globose tangles and neuropil threads characteristic of progressive supranuclear palsy stained with an antibody for tau (which makes it look brown).
Pick bodies in the dentate gyrus of the hippocampus stained with an antibody to tau. These well-circumscribed inclusions are observed in the frontal and temporal lobes as well as limbic structures as depicted here are diagnostic of Pick’s disease.
Ubiquitin positive, tau negative inclusions in the dentate gyrus of a different patient with FTLD. These ubiquitin positive, tau negative inclusions are diagnostic of a distinct disorder that leads to FTLD termed “FTLD-U,” where the U stands for ubiquitin. In most cases of FTLD with ubiquitin inclusions, there is protein aggregation of the RNA binding protein TDP-43, which also aggregates in the motor neurons of patients with ALS.
