Taking Charge of Your Health

Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
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much more. Try it free today! 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.

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