oncology

Hemangiopericytoma: A Tumor of Pericytes

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In order to understand hemangiopericytomas we have to define a few terms. The first term is mesenchyma. Mesenchyma is a word used to describe the different tissues that provide structure to the bodies’ organ systems. A type of mesenchymal cell known as a “pericyte” provides structural support to blood vessels. When pericytes go haywire they form hemangiopericytomas.

Hemangiopericytomas can occur anywhere blood vessels are located, but are most commonly located in the lower extremities, pelvis, head, and neck.

Intracranial hemangiopericytomas are uncommon. They represent less than 1% of tumors within the confines of the skull. They typically arise from blood vessels adjacent to the dura (ie: lining of the brain) and often form dural attachments. They are therefore commonly lumped into the category of “dural-based tumors”, but should be distinguished from their more benign meningeal cousins (ie: meningiomas).

Since hemangiopericytomas are mesenchymal in origin, they typically have lots of reticulin (a collagen fiber) that envelopes individual cells (see pathology slide). They are highly cellular tumors, and vascular channels in the shape of "staghorns", may be seen under the microscope. Actively dividing cells (aka: "mitotic" figures) are commonly seen and are a testament to their more malignant nature. Unlike meningiomas, calcifications are absent.

Hemangiopericytomas test positive for vimentin (a marker of connective tissue), Ki-67 (a marker of proliferation), vascular endothelial growth factor (VEGF, a marker of blood vessel proliferation), CD34 (a marker of blood and vascular cell lineage), and reticulin (a collagen fiber). These tumors do not stain positive for epithelial membrane antigen. Genetic mutations have been found on different chromosomes , but the importance of these abnormalities is not well understood.

Intracranial hemangiopericytomas are considered malignant tumors. This means that they can spread to other areas of the body. In addition, hemangiopericytomas that have been removed surgically have a high recurrence rate.

Hemangiopericytoma

Signs and Symptoms

Hemangiopericytomas are relatively slow growing and often do not cause symptoms until they become quite large. However, once they start to compress adjacent brain tissue they may cause headaches, seizures, confusion, weakness, or visual problems.

Diagnosis

MRIs and CT scans of the brain typically reveal a contrast enhancing dural-based lesion. Cerebral angiograms show a highly vascular tumor with blood supply coming from the dura, as well as the underlying brain tissue.

Based on imaging alone, hemangiopericytomas are often mistaken for meningiomas. Subtle characteristics such as a lack of calcification seen on CT scans may help distinguish one from the other, but this is not reliable.

The only reliable way to diagnose hemangiopericytoma is to look at a specimen of the tumor under a microscope. Special stains and features of the tumor can help delineate it from a meningioma (see pathology section above).

Did I Hear Someone Say “Treatment”?

Intracranial hemangiopericytomas should be surgically resected when feasible. Unfortunately, even after complete resection, they frequently recur and/or spread to other areas of the body.

Because of their aggressive nature, patients with hemangiopericytomas should also have adjuvant radiation therapy. Radiation treatment after surgical removal of the tumor has been shown to lengthen survival and slows (but doesn’t appear to prevent) the time to recurrence.

The role of chemotherapy is less clear and is still being investigated. At this point, chemotherapy is typically used in patients where radiation and surgery have failed to control the disease.

Let’s Recap It…

Intracranial hemangiopericytomas are malignant dural-based tumors that arise from pericytes. They are highly vascular tumors that enhance on MRI and CT scans. Symptoms are variable and depend on the size and location of the tumor. Treatment is with surgical removal followed by radiation therapy. Recurrence rates are high despite optimal treatment.

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Ependymoma: Myxopapillary, Anaplastic, and Perivascular Pseudorosettes

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Ependymomas are tumors that develop from cells known as ependymal cells (duh!). Ependymal cells are a type of glial cell that line the ventricles (ie: fluid filled cavities) of the brain and central canal of the spinal cord.

Normal ependyma have cilia and microvilli on the side of the cell that faces cerebrospinal fluid (ie: the "apical" side). Cilia are hair like extensions that are believed to "beat" cerebrospinal fluid around the ventricles. Microvilli are folds in the cellular membrane that are thought to aid in the reabsorption of cerebrospinal fluid.

Unlike other epithelial cells in the body, of which ependyma are considered a subgroup, they do not rest on a basement membrane. Instead their basal surfaces (the surface not in contact with cerebrospinal fluid) intertwine with the overlying brain tissue.

Like any other cell in the body, ependymal cells can decide to turn naughty and form a tumor. Ependymomas can occur anywhere there are ependymal cells, and therefore develop in both the brain and spinal cord. Intracranial ependymomas are more common in younger age groups, whereas spinal forms are more common in older individuals. Of those that form within the confines of the skull, the most common location is in the fourth ventricle near the brainstem.

There are three "grades" of ependymoma. There are two subsets of grade one: myxopapillary and subependymomas. The second grade of ependymoma has four distinct variants. They are cellular, papillary, clear cell, and tanycytic. The third grade is also referred to as "anaplastic" ependymoma. Regardless of the grade, each type has its own distinct characteristics when viewed under the pathology microscope.

Surgical specimens of ependymomas are often "stained" by pathologists to help aid in diagnosis, and more importantly, distinguish them from other tumor types. Ependymomas stain positive for the glial fibrillary acidic protein (GFAP), as well as phosphotungstic acid hematoxylin (PTAH).

Ependymomas may have perivascular pseudorosettes, which helps support the diagnosis. Pseudorosettes may not be apparent in tumors with dense cellularity such as anaplastic ependymomas.

In addition, ependymomas can spread throughout the cerebrospinal fluid space. For example, a tumor that arises in the fourth ventricle may "drop" tumor cells down into the spinal cord forming a secondary tumor. These secondary tumors are referred to as "drop mets".

Signs and Symptoms

The signs and symptoms depend on the location of the ependymoma.

The most common symptom of intracranial ependymoma is headache associated with nausea and/or vomiting. These symptoms occur when the ependymoma blocks the flow of cerebrospinal fluid, which causes a condition known as non-communicative hydrocephalus.

You can think of non-communicative hydrocephalus as a clog in a pipe. Everything upstream of the clog starts to back up, which eventually leads to increasing pressures. When this increased pressure occurs in the ventricular system of the brain it causes worsening headaches, nausea, and vomiting. This is especially true if the ependymoma is in the fourth ventricle of the brain, which even without tumor, is an anatomically narrow "pipe" to begin with.

Additionally, if the tumor pushes on brainstem structures a patient may present with dysfunction of the nerves that go to the various muscles of the head and face. The most commonly involved nerves are the facial nerve, which can cause weakness of the face, as well as the abducens nerve, which can cause weakness of the eye.

Tumors located in the spinal cord cause weakness and sensory disturbances.

Diagnosis

Ependymoma

MRI scans can be very useful and can support (but not prove) the diagnosis of ependymoma, especially when the tumor is in a common anatomical location.

If there is a high index of suspicion for ependymoma then the entire neuro-axis, meaning the brain and entire spinal column, should be imaged using MRI. This will detect “drop” mets, which, if present, further support the diagnosis.

Diagnosis can only be officially made when a sample of tumor (either surgical or at autopsy) is seen under the pathology microscope.

Treatment

Treatment of ependymoma is with surgical resection followed by radiation therapy. Patient outcome is most effective if the entire tumor can be removed during surgery. This is known as "gross total resection". However, the extent of surgical resection should always be weighed against the risk of harming the patient, especially if the tumor has invaded vital structures like the brainstem.

Fortunately, ependymomas are very radio-sensitive, which means that they respond well to getting zapped with radiation. Chemotherapy is not typically helpful except in very young children where the effects of radiation can be devastating.

Overview

Ependymomas arise from the cells that line the ventricular system of the brain and spinal cord. There are different subtypes depending on what it looks like under the pathology microscope. Diagnosis is based on pathological analysis and characteristic MRI findings. Treatment is with surgery and radiation.

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