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Adult brain tumors: Pathology review



Nervous system


Central nervous system disorders
Central and peripheral nervous system disorders
Peripheral nervous system disorders
Autonomic nervous system disorders
Nervous system pathology review

Adult brain tumors: Pathology review


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USMLE® Step 1 style questions USMLE

5 questions

A 54 year-old woman is brought to the emergency department due to a seizure. People in the homeless shelter who witnessed the event report that she fell to the ground and started having rhythmic jerking movement of the limbs. Her medical history is unknown. Physical examination reveals the patient to be dishevelled, confused, and barely responsive. Computed tomography of the head is obtained and shown below before (left) and after (right) the addition of contrast (shown below):  

Credit: Wikimedia Commons

Which of the following is the most likely origin of this patient's primary tumor?  


Content Reviewers:

Yifan Xiao, MD

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. 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. 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. 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. 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. 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. 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. 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.


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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