Pediatric brain tumors: Pathology review

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Case Study0:00–0:46

In the neurology ward, two children came in with the same symptoms: morning headaches, nausea, vomiting, and frequent falls.
One of them is a 12 year old named Greg, and the other is a 14 year old individual named Suzan. Greg’s symptoms started a few months ago and retained the same level of severity, while Suzan’s symptoms started a few weeks ago and are rapidly worsening.
A brain MRI with contrast is ordered for both of them, which showed a well circumscribed cystic lesion in the cerebellum for Greg, and a solid, heterogeneous mass in the cerebellum that compresses the fourth ventricle in Suzan.
Okay, so both Greg and Suzan have pediatric brain tumors. Brain tumors occur when there’s uncontrolled growth of abnormal cells within the brain.

Pathology0:46–3:26

They are broadly classified into primary tumors originating from cells within the nervous system, and metastatic tumors originating from cells outside the nervous system.
Primary brain tumors are the most common solid tumors in children and can be either benign or malignant. Now, for the exams, it’s important to remember that the most common primary brain tumor in both adults and children are gliomas, and more specifically, a subset of these called astrocytomas.
In children, medulloblastomas and ependymomas are next on the list, while in adults gliomas are followed by meningiomas.
Less common brain tumors include craniopharyngioma, pinealomas, pituitary adenomas, oligodendrogliomas, hemangioblastomas, and schwannomas.
Now, metastatic tumors are much more common in adults and are always malignant. In order of decreasing frequency, they most commonly come from cancers of the lung, breast, skin melanomas, kidneys and colon.
Okay, brain tumors can also be categorized based upon their location as either supratentorial, or above the cerebellar tentorium, and infratentorial tumors, or below the tentorium, though some tumors can form in either.
In children, a very high yield concept is that most brain tumors are infratentorial, whereas in adults, they are usually supratentorial, and that’s something you also have to remember for the test!Finally, brain tumors can also be classified, or graded, based upon their severity by the World Health Organization’s scale.
The scale goes from I to IV depending 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 brain tumors have all four grades because some tumors are basically always more benign, whereas others are more aggressive.
Alright, in this video, let’s focus on pediatric brain tumors, starting with tumor types that are generally infratentorial, since they make up the majority of tumors in children.
The most common infratentorial pediatric tumors are pilocytic astrocytoma, medulloblastoma, and ependymoma. Starting with pilocytic astrocytoma, which is the most common primary pediatric tumor.

Pilocytic astrocytoma3:26–4:29

It’s a subtype of astrocytomas which are tumors derived from astrocytes. Astrocytes are glial cells, or non-neuron support cells that protect and support the neurons.
Astrocytes have processes coming off their cell body, giving them a star-shaped appearance. Pilocytic astrocytomas can form anywhere in the brain and spinal cord, but they are mostly infratentorial tumors in the cerebellum or near the brainstem, and this will be a big hint on your exams!
But keep in mind they can also appear less frequently in the hypothalamic region or optic pathways. And while astrocytomas can be graded I through IV, pilocytic astrocytomas are only grade I because they are generally benign and slow-growing.
Keep in mind that in adults, astrocytes can give rise to glioblastomas which are usually supratentorial and high grade. Okay, moving onto medulloblastoma, which is the second most common pediatric tumor.

Medulloblastoma4:29–5:27

However, medulloblastoma is the most common malignant pediatric tumor, since pilocytic astrocytoma is usually benign. Medulloblastomas originate from embryonic stem cells and primitive neuroendocrine cells.
Remember that medulloblastomas also form in or around the cerebellum, just like astrocytomas! A very problematic location that’s high yield is the region adjacent to the fourth ventricle, which is a tent-shaped cavity located between the brainstem and the cerebellum, These tumors tend to be extremely aggressive and 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. Finally, the last common infratentorial tumor is ependymoma.

Ependymoma5:27–6:25

Ependymal cells are also neuroglial cells, and they’re cuboidal-to-columnar, or square-to-rectangular shaped. They are ciliated cells that line the ventricles and central canal.
One of their main roles is to regulate the circulation of cerebrospinal fluid. Ependymomas 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, and that’s something you also have to remember for the exams!
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.
Now let’s switch gears and talk about supratentorial pediatric tumors which include craniopharyngiomas and pinealomas. The most common is craniopharyngioma, which forms near the pituitary gland.

Craniopharyngioma6:25–7:11

During fetal development, neuro ectoderm from the brain evagnates downwards to form the posterior pituitary, while oral ectoderm grows upwards, forming the Rathke’s pouch.
This will pinch off from the oral mucosa and fuse with the tissue above, and they will differentiate into the cells that make up the anterior pituitary.
Now, remnants of Rathke’s pouch that remain undifferentiated can give rise to craniopharyngiomas. And this usually occurs above or around the pituitary.
They’re typically only classified as WHO grade I tumors because they are typically benign and slow growing. Finally, a rare supratentorial pediatric tumor is a pinealoma, which forms in the region of the pineal gland.

Pinealoma7:11–7:27

Pinealomas can arise from the pinocytes or from germ cells. They can be grade I through IV.
Okay, now moving onto symptoms. Individuals with brain tumors typically have some combination of 4 symptoms: headache; focal neurological deficits; a neurocognitive disturbance, that often causes a decline in school or work performance; and psychiatric symptoms including depression.

Symptoms7:27–11:39

The headache is usually dull, slowly progressive, and involves the whole head. It’s high yield so remember that often, it’s worse in the morning and can be accompanied by nausea and vomiting.
As for focal neurological deficits, the pattern depends on the location of the tumor. For example, the involvement of the primary motor cortex would cause weakness, whereas involvement of the primary sensory cortex would cause sensory symptoms, like astereognosis, which is the inability to identify objects by touching them.
Involvement of the language areas can cause different types of aphasia, such as expressive aphasia when Broca’s area is involved, or receptive aphasia when Wernicke’s area is involved.
Now, if the visual pathway is affected, it can lead to a variety of visual field disturbances, like bitemporal hemianopsia, which is blindness in the outer half of both the right and left visual fields.
This can occur with craniopharyngiomas that compress the optic chiasm. In addition, infratentorial tumors can compress cranial nerves causing cranial nerve palsies or compress the cerebellum causing cerebellar symptoms like ataxia and gait instability.
Another focal neurologic finding is that brain tumors can cause focal seizures, and occasionally they can cause generalized seizures as well.Okay, now infratentorial tumors like medulloblastomas and ependymomas, and supratentorial tumors like pinealomas can compress nearby ventricles and obstruct CSF flow.
This can cause obstructive hydrocephalus. Because the skull sutures are still unfused in infants, this can lead to an enlarged head or macrocephaly.
This is actually relatively fortunate, because it means the head can accommodate this mass without causing a rapid increase in ICP and deterioration of the child’s neurological status.On exam, there can be signs of cranial nerve defects as well as signs of increased ICP.
For example, fundoscopic examination of the eyes can reveal papilledema or swelling of the optic disk. Also, Cushing’s triad, which includes hypertension, bradycardia, and an irregular breathing pattern also strongly suggests an increased ICP.
Alright, now there are some clues that can help you distinguish the different tumor types. Infratentorial tumors, including pilocytic astrocytomas, medulloblastomas and ependymomas, typically present with headache, accompanied by nausea and vomiting, cerebellar symptoms like ataxia and gait instability, and visual disturbances.
As for supratentorial tumors, craniopharyngiomas which arise above the sella turcica where the pituitary gland sits, can compress the pituitary gland, causing disturbances in growth and pubertal development in children.
Finally, pinealomas cause Parinaud syndrome, a unique syndrome that results from the tumor compressing the dorsal midbrain, which is below the pineal gland.
The classic triad includes paralysis of upward gaze, pupillary light-near dissociation; which means the pupils react to near objects, but not to light, and thirdly convergence-retraction nystagmus, which is oscillation of the eyes inwards, or convergence, and backwards, or retraction.
However, this syndrome is not unique to pineal gland tumors, and happens to occur in cases of obstructive hydrocephalus, multiple sclerosis, and strokes.
What is relatively unique to pinealomas is that they can secrete hCG which can lead to precocious puberty in males. Alright, let’s look at diagnosis.

Diagnosis11:39–14:56

If a brain tumor is suspected, the next step is a brain MRI with contrast, which is optimal for identifying soft tissue structures like tumors.
Sometimes a CT can be helpful as well, because it can more easily identify calcifications, which are seen in some types of brain tumors like craniopharyngiomas.
Another helpful tip is that pilocytic astrocytomas and craniopharyngiomas can appear cystic, while medulloblastomas and ependymomas are solid tumors.
Okay, but to accurately make the diagnosis of a brain tumor, a tissue sample is needed for histopathological and molecular studies.
This sample can be obtained by stereotactic biopsy or by surgical resection of the tumor. In addition to the histopathological type and grade of the brain, an emphasis has been recently placed on identifying the unique molecular markers of different brain tumors, as they aid in treatment decision making.
Examples include isocitrate dehydrogenase, or IDH mutations in gliomas, or WNT-activating mutations in medulloblastoma. Now, it’s also important to remember some histologic findings, since they might be the best clues for identifying each specific tumor type!
Pilocytic astrocytomas are typically well-differentiated neoplasms which can have cysts and bodies of granular material.
They also have 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. Next, medulloblastomas can have small, round, blue cells since they are neuroendorine in origin.
A high mitotic index is also common. Medulloblastomas also have a histologic feature called Homer-Wright rosettes, which are dense tangles of neurons and neuroglial cells, surrounded by ring-like structures formed by tumor cells.
Keep in mind that this can also appear in pinealomas as well as other brain tumors. As for ependymomas, a prominent histological feature are their perivascular pseudorosettes, which are ring-like structures formed by tumor cells with rod-shaped ependymal processes, like cilia, surrounding a centralized blood vessel.
Moving onto craniopharyngiomas. These are pretty complex tumors with lots of prominent features including multiple cysts filled with a thick “motor-oil”-looking fluid and cholesterol crystals.
Tumor cells also 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.
Finally, prominent features of pinealomas include large, round tumor cells resembling germline tumors.Allright, as a quick recap, pediatric brain tumors are usually primary tumors that originate from cells within the central nervous system and they are located below the tentorium, or infratentorial.

Review14:56–15:40

Pilocytic astrocytoma is the most common pediatric tumor and it’s typically benign, while medulloblastoma is the most common malignant pediatric tumor.
Another common infratentorial tumor is ependymoma. Supratentorial brain tumors include craniopharyngiomas and pinealomas.
Diagnosis can be made with imaging tests like brain CT and MRI scans, as well as tissue biopsy. Now, back to the patients!
Due to their symptoms and the brain MRI results, both Greg and Suzan have a brain tumor. Due to their age, they most probably have a primary brain tumor.

Summary15:40–16:22

Both tumors are infratentorial and so, they most likely have either pilocytic astrocytoma, medulloblastoma, or ependymoma.
Greg’s cystic lesion in the cerebellum is more typical of pilocytic astrocytoma, while Suzan’s lesion, which is a heterogenous mass adjacent to the fourth ventricle, could be either medulloblastoma or ependymoma.
To accurately make the diagnosis, tissue biopsy must be done.