Neuropathology Rotation Flashcards
Reactive astrogliosis
Very common in any structural pathology of the CNS
Astrocytes multiply and extend their processes, thickening the neuropil background.
Can be best appreciated via the GFAP stain (glial fibrillary acidic protein). GFAP becomes thicker and brighter staining as you draw closer to the lesion in many neurological specimens.
Protoplasmic astrocyte
Found all throughout gray matter.
Morphologically characterized by several stem branches in a uniform globoid distribution.
Fibrous astrocyte
Found all throughout white matter.
Morphologically characterized by several long, fiber-like projections that are sparser, longer, and more disorganized than those of a protoplasmic astrocyte.
Astrocyte functions and triggers of reactivity
Markers of active astrocytes
GFAP
S100-beta
Glutamine synthetase
Astrocyte physiology
Astrocytes are not neurons, and they do not “fire” or generate action potentials. However, they do exhibit regulated increases in intracellular Ca2+ which may be triggered by extracellular stimuli or connected astrocytes.
This calcium flux results in the release of glutamate into the extracellular space, triggering local glutaminergic neurons and other astrocytes.
They also play several housekeeping roles in the CNS, one of which is to express transporters that sequester extrasynaptic glutamate, purines, GABA, and glycine.
Features of mild to moderate astrogliosis
Variable GFAP level and astrocyte hypertrophy
No astrocyte proliferation
Associated with: Non-penetrating, non-concussive trauma, diffuse innate immune activation (systemic infection), distance from structural CNS lesion
Is there background levels of GFAP expression in healthy neuropil?
No - it plays a role in reactivity and is only upregulated upon reactive astrogliosis.
Features of severe astrogliosis
Pronounced upregulation of GFAP
Astrocyte proliferation
Astrocytic hypertrophy
Formation of dense astrocyte barriers (glial scars) bordering necrotic tissue.
Key features to aid in identifying neural tumors
Age of the patient
Location of the tumor
Radiographic appearance
Demyelinating lesions
The major non-malignant differential for CNS tumors
Often looks like a tumor on radiology, but pathology reveals numerous foamy macrophages and an absence of apparently malignant cells.
This is also the appearance of an infarct, with some added liquefactive necrosis.
Features of astrocyte hypertrophy seen in gliosis
1: Normal astrocytes should have no visible cytoplasm. In gliosis, they often develop visible, densely pink (almost oncocytic) cytoplasm.
Evaluating a CNS tumor: how is it clinically different?
1: Malignant potential matters less. The blood brain barrier also protects the blood – primary brain tumors do not tend to metastasize, even the mean ones. So, we do not TNM stage brain tumors, examine margins, or size tumors. Instead, the main form of evaluation is in WHO grading.
How WHO grading works for tumors of the CNS
Most neoplasms are assigned a grade by definition: ie, if you have x tumor, it is grade 2.
Some have a spectrum of grades based on histologic features (especially astrocytic tumors). Reasons to a higher grade may include:
- Cytologic atypia (subjective)
- Increasing cellularity relative to lowest-grade tumor (subjective)
- Increasing number of mitoses (quantitative)
- Microvascular proliferation (present or absent)
- Necrosis (present or absent)
WHO grading “anaplastic” qualifier
Means that the tumor is grade 3
For example, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ependymoma
WHO grading “blastoma” qualifier
Means that the tumor is grade 4
For example, glioblastoma
Different preps of a neural lesion and what to look for in each
1: Smear/touch prep – smears are great for identifying fibrillary processes characteristic of glial tumors. Nuclear detail is also well preserved on smear, and you can get a sense of cohesion.
Diffuse astrogliomas are also divided into. . .
. . . IDH mutant and IDH wild-type
This has significant prognostic impact
Subependymal giant cell astrocytoma
A tumor of the lateral ventricles consisting of very large cells with a somewhat ganglionic appearance.
Classically associated with tuberous sclerosis complex.
Tumor that looks like a meningioma on imaging, but then you see this on biopsy
Solitary fibrous tumor / Hemangiopericytoma
This is a staghorn vessel, characeristic of the tumor. The tumor is also blue and highly cellular, in contrast to many pink and whorly meningiomas.
Ischemic nerve cell change
Mineralization / Ferruginization
Describes the appearance of dystrophic calcification of neurons. Typically shrunken and basophilic, sometimes with apparent calcium deposits.
Vacuolated neuropil and neurons
A pathologic hallmark of CJD
Neuronal lipofuscin accumulation
A histopathologic hallmark of an aging brain, or a characteristic of “ceroid lipofuscinosis”, a neuronal storage disorder.
The pigment is also PAS positive and Luxol fast blue positive.
Pick bodies
Round, homogeneous intracytoplasmic neuronal inclusions characteristic of Frontotemporal dementia, where they are seen in pyramidal cells, dentate granule cells, and other affected areas.
The structure is immunoreactive with tau, 3R-tau isoform, ubiquitin, and tubulin. They are masses of intermediate filaments with entrapped vesicular structures.
Hirano bodies
Brightly eosinophilic, rod-shaped or elliptical cytoplasmic inclusions that often overlap with the cell border of a neuron cell body.
They are found in Alzheimer’s disease, FTD, and Guam parkinsonism-dementia complex.
They are immunoreactive for actin and actin-associated proteins.
Bunina bodies
Eosinophilic, nonviral intracytoplasmic inclusions found in motor neurons in familial or sporadic ALS.
They are immunoreactive for cystatin C.
Skein-like inclusions
Abnormal, ubiquitinated, p-62 positive structures occurring in anterior horn cells in motor neuron diseases, such as ALS.
Linear, thread-like structures that occur in a single inclusion or form networks of threads. These inclusions contain TDP-43.
Marinesco bodies
Small, eosinophilic, intranuclear inclusions. Strongly ubiquitin positive. (intranuclear in image, ignore the cytoplasm)
Suggest different diseases depending upon their location (namely, inside of outside of the substantia nigra and locus ceruleus).
