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Pediatric brain tumors are masses of abnormal cells that generally occur in children, and
result from the uncontrolled growth of those cells within the brain.
OK - let’s start with some basic brain anatomy.
First off, there’s the cerebral cortex which is the part of the brain that’s supratentorial
or above the tentorium, and the cerebellum, which is infratentorial or below the tentorium.
And the brain has four interconnected cavities called ventricles, which are filled with cerebrospinal
fluid - a fluid that helps provide buoyancy and protection, as well as metabolic fuel
for the brain.
Highest up, are two C-shaped lateral ventricles that lie deep in each cerebral hemisphere.
The two lateral ventricles drain their cerebrospinal fluid into the third ventricle, which is a
narrow, funnel-shaped, cavity at the center of the brain.
The third ventricle makes a bit more cerebrospinal fluid and then sends all of it to the fourth
ventricle via the cerebral aqueduct.
The fourth ventricle is a tent-shaped cavity located between the brainstem and the cerebellum.
After the fourth ventricle, the cerebrospinal fluid enters the subarachnoid space, which
is the space between the arachnoid and pia mater, two of the inner linings of the meninges
which cover and protect both the brain and the spine.
So this makes it possible for cerebrospinal fluid to also flow through the central canal
of the spine.
Now, focusing in on cells within the brain - there are many different types with specialized
functions.
For example, neurons communicate neurologic information through neurotransmitter regulated
electrical impulses.
Then there are cells that secrete hormones into circulation and regulate the functions
of other cells throughout the body.
These cells are found in glands, like the supratentorial pineal gland which is located
just behind the third ventricle.
Or the infratentorial pituitary gland located near the front of the third ventricle.
There is also a category of cells called neuroglial cells that help support brain homeostasis,
and neuronal functions.
These include astrocytes which have cellular processes coming off their cell body, giving
them a star-shaped appearance.
Astrocytes are found throughout the brain and spinal cord, and their main roles include
maintaining the blood-brain barrier, providing nourishment to neurons, and recycling neurotransmitters.
Ependymal cells are also neuroglial cells, and they’re cuboidal-to-columnar - so square
to rectangular shaped - ciliated cells that line the ventricles and central canal.
One of their main roles is to regulate the circulation of cerebrospinal fluid.
Some brain cells have a limited ability to be replaced, especially during injury, and
they do it by having undifferentiated stem cells - called embryonic stem cells - in the
brain activate and mature into a specialized cell.
Now, a tumor develops if there’s a DNA mutation in any of these cell types that leads to uncontrolled
cell division.
Typically these are mutations in proto-oncogenes which results in a promotion of cell division,
or mutations in tumor suppressor genes which results in a loss of inhibition of cell division.
You can think of proto-oncogenes as the accelerator or gas pedal and tumor suppressor genes as
the brakes.
Too much acceleration or an inability to brake can lead to runaway cell division.
As a result, the mutated cells can start piling up on each other and can become a tumor mass.
Some of these tumors are benign and stay well contained or localized.
But some become malignant tumors or cancers, and these are the ones that break through
their basement membrane and invade nearby tissues.
Malignant tumor cells can get into nearby blood or lymph vessels, and travel from the
primary site to establish a secondary site of tumor growth somewhere else in the body
- and that’s called metastasis.
Brain tumors can be categorized by their primary site location as either supratentorial, or
infratentorial tumors – though some tumors can form in either.
They are typically named by the cell type involved, so for example an astrocytoma is
a tumor formed by mutated astrocytes.
But their severity is classified, or graded by the World Health Organization’s (WHO)
scale.
The scale goes from I to IV based on the morphologic and functional features of the tumor cells;
a grade IV tumor being the most abnormal looking cells that also tend to be the most aggressive.
But not all tumors have all four grades because some tumors are basically always more benign,
whereas others are more aggressive.
So let’s start with tumor types that are generally infratentorial tumors, because they
make up the majority of pediatric brain tumors.
Overall, the most common malignant tumor is a medulloblastoma, which typically forms in
or around the cerebellum, adjacent to the fourth ventricle.
Medulloblastomas originate from embryonic stem cells and they tend to be extremely aggressive.
One relatively unique feature is that they metastasize through the cerebrospinal fluid
in a process called drop metastasis where the tumor spreads to the base of the spine.
Because of this, medulloblastomas are typically only classified as grade IV.
Histologically, medulloblastomas often have a feature called Homer-Wright rosettes, which
are dense tangles of neurons and neuroglial cells, surrounded by ring-like structures
formed by tumors cells.
Now, while medulloblastoma may be the most common malignant tumor, the most common primary
pediatric tumor is a type of astrocytoma called a juvenile pilocytic astrocytoma.
Because astrocytes are found through the brain and spinal cord, astrocytomas can form throughout
those locations, but juvenile pilocytic astrocytomas are mostly infratentorial tumors in the cerebellum
or near the brainstem.
And while astrocytomas can be graded I through IV, juvenile pilocytic astrocytomas are only
grade I because they are generally benign and slow-growing.
Histologically, they can have cysts, or sacs filled with fluid; bodies of granular material;
and Rosenthal fibers, which are fibers that clump together in the cytoplasm of the astrocyte
and look a bit like a worm or a corkscrew.
Among the fibers is the structural protein glial fibrillary acidic protein that is typically
found in astrocytes.
Finally, another common infratentorial tumor is an ependymoma.
Now, again, they can form in the brain and spinal cord because that’s where ependymal
cells are found, but pediatric ependymomas tend to form in the fourth ventricle.
Now, there are a few types of ependymomas and they’re WHO graded I through III.
In grade II, classic ependymomas, tumor cells have a regular, round to oval nucleus.
Histologically, a prominent feature are their perivascular pseudorosettes, which are ring-like
structures formed by tumors cells with rod-shaped ependymal processes, like cilia, surrounding
a centralized blood vessel.
Ok, so, now let’s focus on supratentorial pediatric tumors.
The most common is a craniopharyngioma, which forms near the pituitary gland.
During development, some cells migrate down from the brain and form the posterior pituitary;
while some cells migrate up from the back of the throat, called the oropharynx, first
forming the Rathke’s pouch and then eventually forming the anterior pituitary gland.
Now, remnants of Rathke’s pouch that do not mature can form craniopharyngiomas.
They’re typically only classified as WHO grade I tumors because they are typically
benign and slow growing.
Histologically, it’s a pretty complex tumor with lots of prominent features including
multiple cysts filled with a thick “motor-oil”-looking fluid; and cells that stratify, or arrange
themselves in layers.
The innermost layer tends to have loosely packed cells that retain their nuclei despite
being filled with keratin, a strong protein, creating what’s called a “wet keratin”
appearance.
A rare supratentorial pediatric tumor is a pinealoma, which forms in the region of the
pineal gland.
Pinealomas primarily emerge from the endocrine cells of the pineal gland, and they can be
grade I through IV.
Histologically, prominent features include large, round tumor cells resembling germline
tumors; or small cells forming Homer-Wright rosettes.
Now, the most common symptoms of brain tumors include headaches, nausea, vomiting, and seizures
- and they are a result of the compression and destruction of healthy brain tissue.
In addition, it’s important to consider the cell type that’s involved.
So, for example, a pinealoma may lead to increased secretion of the hormone beta human chorionic
gonadotropin that can cause an early onset of puberty.
In addition, as the tumor grows in size, it can compress nearby cells and structures,
interrupting their normal functions.
For example, as pinealomas, medulloblastomas, and ependymomas enlarge - the mass of the
tumor can compress nearby ventricles blocking the flow of cerebrospinal fluid which causes
swelling, called hydrocephalus.
Generally, the diagnosis of central nervous system tumors includes medical imaging, like
CT scans but more commonly MRIs.
But definitive diagnosis needs to be made based on the histologic and molecular characteristics
of a tissue biopsy.
Treatments depend on the tumor type, grade, and symptoms.
And can include surgical removal, radiotherapy, or chemotherapy - frequently in a combination.
But specific courses of treatment are guided by the molecular characteristics of the tumor
based on the biopsy.
Finally, the chance of recurrence gets higher in high grade tumors and in tumors that have
not been fully removed or destroyed.
Ok, quick recap: Pediatric brain tumors can be infratentorial and supratentorial and form
from a variety of cells.
Tumor types are classified using WHO grading based on histologic and functional features.
Diagnosis includes medical imagining, with a definitive diagnosis being made with a tissue
biopsy.
Treatments are largely dependent on the molecular characteristics and tumor grade, and can incorporate
surgical removal and some combination of radiotherapy
and chemotherapy.