Adult brain tumors: Pathology review

Definitions & Key takeaways

Adult brain tumors are tumors that occur in adults. The most common type of adult brain tumor is glioma, which arises from the glial cells that support the nerve cells in the brain. Other types of adult brain tumors include meningiomas (tumors that arise from the meninges, which are the membranes surrounding the brain and spinal cord), schwannomas (tumors that arise from Schwann cells, which support the nerve fibers), and astrocytomas (tumors that arise from star-shaped cells called astrocytes).

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Case study0:00–1:17

In the neurology ward, a 64-year old female, named Angela, came in complaining of morning headaches along with nausea and vomiting for the past few weeks.
Her husband says that her personality has changed over the last few weeks and she seems more aggressive. Brain MRI revealed a mass in the frontal lobe.Tissue biopsy shows a pseudo-palisading pattern with necrosis in the middle and viable cells lining up in the periphery.Now, next to Angela, there’s Jerry, a 59-year old male who’s also having morning headaches for the past few months.
A brain MRI is ordered and reveals a mass on the brain surface, just under the dura mater. Tissue biopsy shows psammoma bodies.
Finally, there’s a 40-year old male, named Dan, who complains of ringing in the ears and hearing loss on one side. A brain MRI is done, and showed a mass on the cerebellopontine angle.
Tissue biopsy shows a mass with biphasic appearance with alternating hypercellular and hypocellular regions. Tumor cells stain positively for S100.Okay, Angela, Jerry, and Dan all had brain tumor.

Pathology1:17–6:10

Brain tumors occur when there’s uncontrolled growth of abnormal cells within the brain. They are broadly classified into primary tumors originating from cells within the nervous system and metastatic tumors originating from cells outside the nervous system.Now, brain tumors can occur in both children and adults.
In this video, let’s focus on adult brain tumors. In adults, metastatic tumors are much more common than primary tumors, in fact, they account for more than half of the cases.
In order of decreasing frequency, they metastasize from the lung, breast, melanoma from the skin, kidneys, and colon. Now, the most common primary brain tumor in adults is glioblastoma multiforme, which is a type of astrocytomas.
Meningiomas and pituitary adenomas are next on the list. Less common brain tumors include oligodendrogliomas, hemangioblastomas, and Schwannomas.
immunocompromised people, like organ transplant recipients or individuals with AIDS, are at high risk of primary central nervous system lymphoma caused by the Epstein-Barr virus.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, most brain tumors are infratentorial, whereas in adults, they are usually supratentorial, and that’s something you must know for the test!
Glioblastomas multiforme, meningiomas, pituitary adenomas and oligodendrogliomas are generally supratentorial, whereas hemangioblastomas and schwannomas are usually infratentorial.
Metastatic tumors can arise in both regions.Finally, brain tumors can also be classified, or graded, based upon their severity on 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 typically more benign, whereas others are more aggressive.All Right, let’s look at the Causes of brain tumors in general.
The main environmental risk factor for brain tumors is exposure to ionizing radiation, which can come from therapeutic radiotherapy for cancer, or diagnostic imaging like CT scans.
Electromagnetic radiation from cell phones and microwaves is currently being researched as potential risk factors in humans.
Another concept that is frequently tested on the exams is that Meningiomas are particularly more common in women, possibly because the tumor cells possess estrogen and progesterone receptors.Now, a small proportion of brain tumors occur secondary to genetic syndromes.
For example neurofibromatosis type 1 is associated with optic nerve gliomas and schwannomas, whereas neurofibromatosis type 2 is associated with bilateral schwannomas.
Both are associated with meningiomas, which can also arise in people with multiple endocrine neoplasia type 1. Tuberous sclerosis is associated with subependymal giant cell astrocytomas.
The word “subependymal” literally means under the ependymal cells which line the cerebral ventricles, so these tumors are commonly found along the border of the lateral ventricles.
Turcot syndrome is a rare polyposis syndrome that increases the risk of colonic polyps and colorectal cancer, but also increases the risk of brain tumors, specifically gliomas and medulloblastomas.All right, now let’s take a closer look at the different types of supratentorial adult brain tumors, since they make up the large majority in adults.
The most common supratentorial adult tumors are glioblastomas multiforme, meningiomas, pituitary adenomas, and oligodendrogliomas.
Let’s start with glioblastoma multiforme which is a type of astrocytoma. Because astrocytes are found throughout the brain and spinal cord, astrocytomas can form in all of these locations, but glioblastomas are most common in the cerebral hemispheres.
And while astrocytomas can be graded I through IV, glioblastomas are only grade IV because they are highly malignant tumors.
Because of their quick growth and invasion of nearby tissues, glioblastomas tend to rapidly cross the corpus callosum, creating what’s called a “butterfly glioblastoma.”Cancer cells typically recruit blood vessels to provide them nourishment in a process called angiogenesis, but glioblastomas proliferate so fast that even with angiogenesis their nutrient demand outpaces the blood supply.

Glioblastoma multiforme6:10–7:17

As a result, because the blood supply serves the peripheral tumor cells first, the tumor cells at the center of the tumor die off creating necrotic regions with viable cells around the edges.
Another common supratentorial tumor is a meningioma. Meningiomas come from cells found in the arachnoid mater of the meninges, called arachnoid cap cells, and they often attach to the dura mater.
Since these tumors are not within the brain parenchyma, they are also called extra-axial tumors.They typically form in parasagittal regions of the brain but they can also arise on the spinal cord.
They are graded I through III and tend to be relatively slow growing. Next up is the pituitary adenoma, which is formed in the pituitary gland by hormone secreting cells of the anterior pituitary.
There are several cell types in the anterior pituitary that each secrete a tightly regulated level of a particular hormone; for example, lactotroph cells secrete the hormone prolactin.

Meningioma7:17–7:46

Pituitary adenomas are typically benign so they’re classified by the hormone that’s released as the tumor forms, and by the size of the tumor; rather than using the standard WHO classifications.Now, a relatively rare supratentorial tumor is an oligodendroglioma.
Because oligodendrocytes are found throughout the brain and spinal cord, oligodendrogliomas can form in any of these locations, but adult oligodendrogliomas typically form in the frontal lobes of the cerebral cortex because those neurons are the most heavily myelinated.

Pituitary adenoma7:46–8:23

These tumors are categorized as grade II or III, with an overall tendency to be relatively slow-growing tumors, though they still have the ability to become malignant.Okay, so, now let’s focus on infratentorial adult tumors, such as hemangioblastoma.
Hemangioblastomas are tumors that derive from cells with blood vessel origins, so while they can develop anywhere in the brain they are most often found in the cerebellum, especially in a middle-aged person.

Oligodendroglioma8:23–8:57

They are slow-growing tumors and are typically grade I.Hemangioblastomas are associated with Von-Hippel-lindau syndrome, a genetic disorder that causes many different types of tumors, like clear cell renal carcinoma, pancreatic tumors, and adrenal tumors that cause pheochromocytoma.
In the head, it causes hemangioblastomas in the brain and retina, but also endolymphatic sac tumors in the inner ear.Finally, schwannomas are found outside the brain.
They arise from Schwann cells which are a subtype of glial cells that surround and support the peripheral nervous system neurons.

Hemangioblastoma8:57–9:46

They arise in the nerves of the trunk, arms, or legs. They are usually slow-growing and benign meaning that the cells don’t invade surrounding tissue structures.
Now, a small number of schwannomas are related to a disease called neurofibromatosis type 2. In neurofibromatosis type 2 there’s a deletion on chromosome 22.
This mutation inactivates merlin, allowing Schwann cells to divide uncontrollably. As a consequence, several schwannomas develop in multiple locations.For the exams, a high yield fact is that it causes schwannomas on both vestibulocochlear nerves, at the cerebellopontine angle, and are known as vestibular schwannomas, or acoustic neuromas.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 work performance; and psychiatric symptoms including depression.

Schwannoma9:46–10:44

The headache is usually dull, slowly progressive, and involves the whole head. 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 frontal lobe can cause personality changes, while the 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.

Symptoms10:44–13:48

For the tests, also remember that vestibular schwannoma causes bilateral hearing loss, tinnitus, and problems with balance.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 classically occurs with pituitary tumors that compress the optic chiasm.In addition, 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.
Now, it’s also important to consider the cell type that’s involved. So, for example, a pituitary adenoma causing an increase in prolactin secretions may lead to amenorrhea in women and infertility in men.Hemangioblastomas, on the other hand, can secrete erythropoietin which leads to polycythemia.In addition, as the tumor grows in size, it can compress nearby cells and structures, interrupting their normal functions.
For example, as meningiomas enlarge, the mass of the tumor can compress nearby ventricles blocking the flow of cerebrospinal fluid, causing swelling which results in obstructive hydrocephalus and an increase in intracranial pressure, or ICP.
Findings that strongly suggest an increased ICP are papilledema, or swelling of the optic disk on fundoscopy as well as Cushing’s triad.
Remember on your exams that this is hypertension, bradycardia, and an irregular breathing pattern.All right, for diagnosis, 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 oligodendrogliomas.
For imaging, remember that tumors arising in different regions of the brain are more likely to be due to metastasis.Both glioblastomas, and metastatic tumors can show ring-enhancing lesions, where areas of low density appear dark and they’re surrounded by a ring of high density tissue, appear bright white.
Don’t confuse these with brain abscess and multiple sclerosis which also have ring enhancement!Okay, 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. The next clue for diagnosis can be the unique molecular markers associated with certain types of brain tumors.Examples include isocitrate dehydrogenase, or IDH mutations in gliomas, or WNT-activating mutations in medulloblastoma.
Stains are also helpful. Remember that astrocytomas and oligodendrogliomas derive from glial cells, so they stain positively for glial fibrillary acidic protein, or GFAP.

Diagnosis13:48–17:58

Metastatic tumors will have marker or stain for the primary tumor, for example, melanoma will be positive on S100 antibody stain, but keep in mind this is also positive in schwannomas.
Now, it’s also important to remember some histologic findings, since they might be the best clues for identifying each specific tumor type!Let’s start with glioblastoma multiforme.
Histologically, it appears like the cells of the tumor are lining up like fence posts against the necrosis in the middle, producing a characteristic pseudo-palisading pattern.Next up, meningiomas form nests of cells or a multinuclear mass of fused cells, which have an appearance like a wave in the ocean.
Another high yield fact is that these tumors may also cause the formation of calcifications called psammoma bodies. Psammoma bodies are round, eosinophilic structures that can also be seen in papillary thyroid carcinoma and serous papillary ovarian adenocarcinoma.Now in pituitary adenomas, the particular hormone secreting cell that’s causing the pituitary adenoma will increase in number.
As for oligodendrogliomas, remember that prominent features can vary; Grade II tumors have fairly small, round nuclei, surrounded by well-defined “halos” or thick, white cytoplasm, giving them a “fried egg” appearance.
In Grade III tumors, they have a “chicken wire” pattern of blood vessels with areas of calcifications. All right, now hemangioblastomas are composed of thin-walled capillaries that are arranged close to one another.
Finally, another high yield fact you have to know is that schwannomas have a biphasic appearance, meaning they have alternating regions with different cell patterns, called Antoni A and Antoni B.
Areas with an Antoni A pattern are hypercellular, meaning they have lots of tightly packed Schwann cells with elongated or spindle-shaped nuclei and little surrounding cytoplasm.
They can also have Verocay bodies, which are fibrous cell processes, between two rows of palisading, or lined-up, Schwann cells.
Now, areas with an Antoni B pattern are hypocellular, with fewer, more loosely packed Schwann cells that appear scattered.Okay, as a quick recap!
In adults, brain tumors are usually metastatic tumors originating from cancers of the lung, breast, and melanoma. Primary brain tumors are usually supratentorial and include glioblastoma multiforme, meningiomas, pituitary adenomas and oligodendrogliomas.
Other less common infratentorial tumors include hemangioblastomas and schwannomas. Diagnosis can be made with imaging tests like brain CT and MRI scans, as well as tissue biopsy.Now, back to the patients!
Let’s start with Angela. Tissue biopsy showed a pseudo-palisading pattern which is typical for glioblastoma multiforme.
Jerry’s brain MRI revealed a mass just under the dura mater and tissue biopsy showed psammoma bodies. These are consistent with the diagnosis of meningioma.Finally, Dan presented with hearing loss and tinnitus which are symptoms indicative of acoustic neuroma.
MRI and tissue biopsy confirmed the diagnosis. Finally another high-yield fact that you have to know is it's run Oma's have a biphasic appearance.
Meaning they have alternating regions with different cell patterns. Call Antoni a and Antoni V.
Aries, with an Anthony. A pattern are hypercellular meaning that they have lots of tightly packed Schwann cells, with elongated or spindle-shaped nuclei, and little surrounding cytoplasm.
They can also have their okay bodies, which are fibrous cell processes between two rows of palisading or lined up Van sells a pattern or hypo cellular with fewer more Loosely packed strong sales of your scattered.
Okay, as a quick recap in adult's. Brain, tumors are usually metastatic tumors originated from cancers of the lung breast and melanoma primary brain.

Review17:58–18:35

Tumors are usually, supratentorial. And include glioblastoma multiforme meningioma is pituitary, adenoma and oligodendrogliomas.
Other less common infratentorial, tumors include him and robust Oma's and schwannomas. Diagnosis can be made with imaging tests.
Like brain CT and MRI scans as well as tissue biopsy. No doctor the patients.
Let's start with Angela. Tissue biopsy showed a pseudopalisading pattern, which is typical for glioblastoma.

Summary18:35–19:04

Multiforme. Jerry's, brain MRI revealed a mass just under the dura mater and tissue biopsy shows similar bodies.
These are consistent with a diagnosis of meningioma. Finally Dan presented with hearing loss and tinnitus which are symptoms indicative of acoustic.
Neuroma MRI and tissue biopsy confirm