An Introduction to Neuropathology

The different diagnoses of diseases and disorders within the nervous system are made using neuropathology in coordination with clinical signs/symptoms and imaging. The imaging techniques discussed in Chapter 9 , coalesced with biopsies, the use of selective antibodies to identify cellular markers, and particular stains to highlight cellular structures, are all used to make a diagnosis. This chapter will present some common neuropathological diseases/disorders.

Stains used to help identify the different cells of the central nervous system (CNS) include hematoxylin and eosin (H&E), Nissl stain, Luxol-fast blue stain, and silver stains. H&E stains are the most commonly used, with the cytoplasm of cells being more acidic (eosinophilic) and staining red, whereas the nuclei and nucleoli are more basic (hematoxylinophilic) and are stained blue. Nissl bodies, which are the rough endoplasmic reticulum of neurons, are basophilic, and the use of a Nissl stain (cresyl violet) results in a dark purple highlight of the rough endoplasmic reticulum. Axons and dendrites cannot be distinguished unless there are swelling-related changes. Astrocytes lack an eosinophilic cytoplasm and have nuclei that appear large and quite clear. When astrocytes react to tissue damage, they appear eosinophilic because their cytoplasm becomes more abundant as a result of an increase in fibrous components, which also accumulate in the nerve processes. Oligodendroglia are smaller than astrocytes, with basophilic densely staining nuclei and a barely visible cytoplasm. The nuclei of microglia present with basophilic club-shaped terminations and are thus easily distinguished. Luxol-fast blue stains the myelin sheath (lipids) blue and is often used to help diagnose demyelinating diseases.

Silver stains (i.e., Bodian staining) use silver, copper, and gold to stain neuronal cell bodies and nerve processes dark brown. Parts of the cells that take up the “silver” stain (called argentaffin parts) can include areas of localized axonal swelling, dendritic lesions, and Alzheimer neurofibrillary degeneration (neurofibrillary tangles [NFTs]). Other silver staining procedures enable clear visualization of amyloid components of senile plaques; immunostained images of β-amyloid proteins show similar results.

Primary Brain Tumors

Tumors of the brain include astrocytomas, oligodendrogliomas, and ependymomas, medulloblastomas as well as several others. Originally these primary brain tumors were thought to originate from glial cells, hence the name (gliomas); recent evidence suggest that they may not only come from glial cells but also from neural stem cells and are characterized based on the expression of particular cell markers. Primary brain tumors are classified not only using stains, selective antibodies, and/or their location (i.e., intra-axial = within the brain parenchyma, or extra-axial = outside of the brain parenchyma) but also based on how well defined the borders of the tumor are (i.e., well circumscribed vs. diffuse). In addition, there are tests, such as KI67 staining for identifying mitotic activity, performed in order to detect how rapidly the cancer is dividing, and the majority of tumors are given a “grade” (grades I-IV from slow to fast) for growth aggressiveness.


Astrocytomas are thought to develop from astrocytes and may arise anywhere in the brain or spinal cord (intra-axial), yet they most often occur in the cerebrum. Astrocytomas are the most common primary CNS tumors and can be further divided based on their ability to either remain localized or diffusely infiltrate.

Figure 10.1

(A) Pilocytic astrocytoma MRI-T1, parasagittal view and (B) MRI-T1 gadolinium enhanced axial view (arrows) . The more localized, slow growing astrocytomas (i.e., grade I) are called pilocytic astrocytomas . These typically well-circumscribed tumors are found more often in children and young adults in areas like the cerebellum, but they are not limited to the cerebellum. These tumors are highly vascular and enhance well with contrast injection. They are often cystic (*) with a protruding solid nodule. (C) Pilocytic astrocytoma of the pons. Though more common in the cerebellum and hypothalamus, pilocytic astrocytoma may occur anywhere. As this example illustrates, pilocytic astrocytoma is frequently grossly cystic. Many cystic pilocytic astrocytomas have a solid mural nodule. (D) Biphasic (cystic and solid) pilocytic astrocytoma with numerous Rosenthal fibers (arrows) . These are cytoplasmic inclusions composed of GFAP (glial fibrillary acidic protein—a marker of neural glial cells), the intermediate filament protein of astrocytes. These types of tumors tend to lack signs of necrosis and mitotic figures with very limited infiltration of surrounding brain. (E) Granular eosinophilic bodies (arrows) are another cellular marker of pilocytic astrocytoma in addition to Rosenthal fibers.

( [A-B] Provided by Dr. Raymond Carmody. [C-E] Provided by Dr. Dimitri P. Agamanolis.)

Infiltrating Astrocytomas

Infiltrating astrocytomas are the most common adult primary CNS (intra-axial) tumor; they are often found in the cerebrum but can also appear in the cerebellum, brainstem, and spinal cord. These types of tumors can range from diffuse astrocytoma (grade II), to anaplastic astrocytoma (grade III), to glioblastoma (grade IV), depending on markers and their speed of proliferation (tumor aggression).

Figure 10.2

(A) Diffuse astrocytoma MRI-FLAIR axial view of the brainstem ( arrows indicating low-grade astrocytoma in temporal lobe). Diffuse astrocytomas are poorly defined and tend to not be well demarcated, but unlike pilocytic astrocytomas they can show signs of infiltration of surrounding brain but often do not enhance using gadolinium. They have a cellular density that is greater than normal white matter with GFAP staining but not as dense as the anaplastic or glioblastoma stages. (B) Diffuse astrocytoma. Low grade cellularity, no atypia or mitoses. The tumor cells show mild atypia and rare mitoses and spread in a diffuse fashion. Diffuse astrocytoma corresponds to WHO grade II. (C) Gemistocytic astrocytoma. The tumor cells are plump with a large eosinophilic cytoplasmic mass (arrows) , similar to certain reactive astrocytes. This is also a WHO grade II tumor. They tend to have some nuclear pleomorphism (i.e., variability in the size, shape, and staining of cell nuclei).

( [A] Provided by Dr. Raymond Carmody. [B-C] Provided by Dr. Dimitri P. Agamanolis.)

Figure 10.3

Anaplastic astrocytomas. MRI-T1 gadolinium-enhanced images of the temporal lobe as well as the midbrain of the brainstem ( [A] axial view, [B] coronal view). Arrows indicate enhancing tumor in cerebral peduncle, mesial temporal lobe, and CSF spaces (extensive CSF “seeding” of tumor). The CSF spread is also causing communicating hydrocephalus. (C) Gliomatosis cerebri. Poorly differentiated glial cells infiltrate the brain and aggregate around blood vessels and neurons. Anaplastic astrocytomas demonstrate dense cellularity, have mitotic figures present demonstrating active proliferation, and have advanced nuclear pleomorphism as compared to the diffuse astrocytomas. Most anaplastic astrocytoma cases are composed of poorly differentiated glial cells, probably astrocytes, that infiltrate the brain diffusely and crowd around neurons and blood vessels (*) and under the pia.

( [A–B] Courtesy Dr. Raymond Carmody. [C] Courtesy Dr. Dimitri P. Agamanolis.)

Figure 10.4

Glioblastoma (previously called glioblastoma multiforme [GBM]) . (A) Grade IV, MRI-T1 with Gadolinium axial view of the tumor crossing via the corpus callosum (arrow) . (B) MRI-T1 with Gadolinium sagittal view (arrow) . These are aggressively growing tumors of the glial cells (i.e., astrocytes, oligodendrocytes) with recent suggestions that neural stem cells may also be a possible origin. Glioblastoma will have mitotic figures displaying rapidly dividing cells that often exhibit nearby necrosis and/or microvascular proliferation. Glioblastomas commonly exhibit a “butterfly appearance” since they can infiltrate through the white matter tracts of the corpus callosum, spreading to both hemispheres. (C) Glioblastoma of the frontal lobe. A large tumor with a variegated appearance due to necrosis and old hemorrhage (arrows) . This is the basis of the term glioblastoma multiforme. Glioblastoma. (D) Viable tumor cells are arranged in a perpendicular (pseudopalisading) fashion around serpiginous necrotic areas (arrows) . Glioblastoma. (E) Microvascular proliferation. The new vessels are often arranged in glomeruloid formations (arrows) and lack a blood–brain barrier. This contributes to cerebral edema and accounts for contrast enhancing in imaging studies. Glioblastomas can be stained for isocitrate dehydrogenase 1 (IDH1) as an important marker for GBM prognosis (IDH1w = poor prognosis [0.8–1.1 years]; IDH1m = better prognosis [2.0–3.8 years]).

( [A-B] Provided by Dr. Raymond Carmody. [C-E] Provided by Dr. Dimitri P. Agamanolis.)


Figure 10.5

Oligodendroglioma. (A) T1-MRI axial image of an oligodendroglioma in the right frontal cortex, (B) MRI-FLAIR image and (C) MRI-T1 with Gadolinium image (arrows) . Oligodendrogliomas are subtle, slowly growing, abnormal proliferations of oligodendrocytes that can be found anywhere in the central nervous system (intra-axial) , yet they are most often found in the frontal and temporal lobes of the cerebral cortex. These tumors often arise in middle-aged adults. Oligodendrogliomas are more circumscribed than astrocytomas. (D) An H&E stained biopsy of a grade II oligodendroglioma demonstrating a blue (hematoxylin stained) nucleus and the appearance of the “fried egg” in which the oligodendroglioma lacks extensions (arrows) . Notice also the rich capillary network (*) , another feature of this neoplasm. (E) Example of perineuronal satellitosis (the accumulation of the oligodendroglial cells encircling a neuron; arrows ). This particular biopsy is classified as grade II (low grade) due to no mitotic figures observed.

Only gold members can continue reading. Log In or Register to continue

Dec 29, 2019 | Posted by in NEUROLOGY | Comments Off on An Introduction to Neuropathology
Premium Wordpress Themes by UFO Themes