AssessmentsPediatric brain tumors
Pediatric brain tumors
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 3-year-old boy is brought to the emergency department by his mother for a tonic-clonic seizure on a background of a 4-week history of unsteadiness on walking. The mother explains that he started walking at 15 months and was steady until 4 weeks ago, when he began to have trouble balancing. The mother also noticed that he has lost 3kg (6.6lb) in the last 2 months despite a healthy appetite. The child has no history of epilepsy and is vitally stable, with no recent fevers or infections. An MRI is ordered and reveals a large tumor in the posterior cranial fossa. A sample of the tumor cells reveals a deletion in the INI1 tumor suppressor gene on chromosome 22. Which subtype of brain tumor is most likely present in this child?
Content Reviewers:Rishi Desai, MD, MPH
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 tumor cells.