02/10/2020

Neuropathology – Pathology of the Nervous System

Neuropathology is done by pathologists as a general specialty. Neuropathology is particularly
difficult as it is a subspecialty dealing with the CNS. The CNS is composed of cells with a very peculiar
lineage of differentiation and function. The neurological diseases which come to the attention of th
epathologists are very rare. It is therefore considered to be a niche sector, and is not performed in
every centres.

The CNS is an anatomic sanctuary, being a closed system. It has meningeal layers, talking with some
parts of the body. Most notably, it is composed of neurons and glia, which are very specific cells
making up a tissue with different functions. The CNS function will not be considered here. Neurons
are the functional/effector parts of the CNS, which communicate by chemical and electrical means.
However, neurons make up the minority of the CNS. The majority is made up by glia, up to 90% of all
CNS cells. Glia are cells deriving from the neuroectoderm, and some from HCS. Their function is to
support the function of the neurons, by providing mechanical support, traffic support and give
protection. They can be considered to be the connective tissue of the CNS.

Tasks and the tools of modern neuro-pathology. A pathology should have expertise in the
oncological field. The pathologist makes a diagnosis of the tumour, classifies the tumour (grading)
and then help in assessing the treatment and the prognosis. The tools a pathologist uses is
morphology (via given things), cytogenetic tools and molecular pathology tools.

Specimens
They can be small biopsies or surgical specimens. They should not be fractioned, and should be sent
in their entirety to the pathology unit. Under standard settings, the pathologist receives all the
specimens taken out by the surgeon. The pathologist should be able to decide what should happen
to the specimen.

The Materials
Use an appropriate container and an appropriate fixative if you’re a pathologist. When you use
multiple samples from different sites, separate in different containers and carefully report the
anatomical location, so that the pathologist can reconstruct what the surgeon has done and what
the diagnosis could be. Fixation is a central part of the pathological assessment. It is a technique
allowing the tissue to be stored for an indefinite time. You could store a specimen in a fixative for
life.

The fixative is the neutral formalin buffered 10%. The cytological material may be sent in alcohol 50-
70% or fresh, by arrangement. The prolonged permanence (i.e. 72h) of the specimen in formalin
leads to over-fixation, which can impair special colorations, immunohistochemistry and molecular
biology. So, fixation can be for a long amount of time but it gives defects.

Cytological Material
Generally represented by spinal fluid or aspiration from cystic cavities. One fo the request of the
surgeon is to see if there are inflammatory or tumoral cells. Hmmmm didn’t get this part 15:00

Stereotactic biopsies
This is mostly performed on surgically untreatable lesions in order to access the non-surgical
therapeutic options, such as radiation therapy or chemotherapy. This technique determines both the
nature and the extent of the lesion. There’s a machine that does it, porco dio very interesting. This is
a well-tested and well-tolerated technique, but may occasionally give rise to haemorrhage.

This though gives you a small specimen, so it has its limitations. You may get the diagnosis, but you
might not have any material left for doing the molecular profiling. Sometimes, the specimen may be
sent for an intraoperative evaluation, which mostly deals with assessing the adequacy of the
specimen. So, the surgeon wants to see if they sampled the lesion or not. The pathologist may then
ask for more material for thediagnosis.

Open-air biopsies
Very rare and infrequent, as they are very invasive. They are done in decompressive interventions
(after a haemorrhage), and the surgeon collects biopsy for a pathological evaluation.

Intraoperative Examinations
This is a very interesting and important point, that all physicians who work in the hospital settings in
the surgical branches of their institution should keep in mind. It is a medical intervention in which a
pathologist is involved, which takes place during the very limited time of the surgical intervention
(performed in parallel). This is done in cases where the diagnosis may change the course of the
surgery. Therefore, this is not done just to establish a diagnosis. This is performed by frozen section
of the specimen. Actually, intraoperative examination is not that infrequent in clinical practice, but it
is a normal part of many of the surgical examinations (such as sentinel lymph node examination in
breast cancer surgery), or for looking for resective margins. In neuropathology, though, it is not very
frequent, which is impaired by different anatomical limitations. CNS is full of fat and water,
especially if you need to take a lesion that is associated with edema. The presence of fat and water
may impair the freezing of the tissue, which will then make it difficult to cut. Nevertheless, there are
instances where this is required.

In order to have a slice of a specimen, the soft specimen should be hardened. You therefore take the
specimen and put it in a chamber with a -20/-25 degrees celcius temperature, freeze it, and use the
sharp blade to cut the specimen in thin slices.

21-10-2020
CROCI
Hemorrhagic Strokes

There are different types of cerebral hemorrhages, epidural, subdural, subarachnoid and
intraparenchymal, which have different etiologies (trauma shared) and different features.

Secondary events hemorrhagic in nature can also happen when one event leads to the other events.

Intraparenchymal
Primary can be caused by hypertension, amyloid angiopathy. It is primary most of the times 80%.
The damage concerns the small vessels of the CNS and chronic damage. Secondary IPH are due to
arteriovenous malformations, aneurysms, tumours or coagulopathies. So, it also affects the larger
vessels.

Extraparenchyma
The other 3 types. Dura is made of 2 layers, periosteal and meningeal. The epidural space lies
between the periosteal dura mater and the skull. Subarachnoid is between the arachnoid mater and
the pia mater. The subdural hematoma is between the meningeal dura mater and the arachnoid
mater. The arachnoid mater pierces the meningeal dura mater to create a tunnel through which the
veins of the brain flow. It can be a cause of subarachnoid haemorrhage secondary to venous vessel
rupture.

Epiidural Hematoma
This is an emergency as the arterial pressure leads to the quick expansion of the epidural space
(which is not very expansible) and it creates a high pressure at the skull, rapidly bringing symptoms
secondary to compression. Transtentorial hernia is when the occipital lobe herniates through the
tentorium after an increase in the pressure, as part of the emergency.

Subdural Hematoma
It can appear in different anatomical compartments, but it is between the pachimeninges and
leptomeninges. These are most commonly secondary to trauma, and due to venous vessel rupture.
These veins can be stretched by the trauma, causing a rotation of the contents within the skull and
these may increase the stiffness of the pachymeninges. This sudden trauma can therefore lead to a
rupture of these bulging veins. When they rupture, the blood pressure is not as high anymore.

Subarachnoid Hemorrhage
Most commonly, it is secondary to a rupture of arterial aneurysms but can also be due to
arteriovenous malformations (or more complex malformations – hemangioma?). It usually has a
more rapid onset of symptoms. The first signs are intense headache which follows into a loss of
consciousness. Consistent with haemorrhage secondary to arterial rupture, there is a high rate of
death after the first event.

Aneurysm
Localized abnormal dilation of the wall of a vessel. It usually occurs in the arteries. They are referred
to as varices when they are present in the veins.

30-10-2020
02-11-2020

Embryonic Tumours

These tumours are generally composed of small cells without a clear-cut morphological
differentaiton.