The Power of Pathology to Detect Disease

Pathology is the study of disease. Pathologists at Northwestern Medicine conduct more than 9 million reportable tests each year to monitor health status, diagnose diseases, determine disease progression, determine drug levels and measure response to treatment. These tests take many forms, from biopsies to blood draws.

Neuropathology is the study of diseases of the nervous system, which includes the brain.

“With surgical neuropathology, we take biopsies, or tissue samples, from resections of brain tumors during surgery to determine diagnosis and prognosis,” says Northwestern Medicine Neuropathologist Craig M. Horbinski, MD, PhD. “We can tell if the tumor is low-grade or malignant, what kind of cancer is present, the grade of the cancer and more recently, we can examine the tumor on the molecular level to improve diagnostic accuracy and determine how to best treat it — which can be different for each patient.”

A Closer Look

Tumors can look identical under the microscope, but have very different prognoses depending on the person and their genetics. After years of studying brain tumors under the microscope, Dr. Horbinski, a member of the Lou and Jean Malnati Brain Tumor Institute of Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, was a part of a team that discovered a molecule that showed promise against an aggressive type of pediatric brain tumor, and was the lead author of a study that identified a correlation between tumor-associated epilepsy and a genetic mutation within the tumor.

Dr. Horbinski is one of many physician-scientists at Northwestern Medicine who take patient-based bedside observations to the lab bench for further analysis. “We then can take what we discover in the lab and apply it back to the bedside to provide better care for our patients,” he says.

Here’s a glimpse of some of the tissue that Dr. Horbinski analyzes in his Neuropathology Lab. See if you can pick out the patterns he describes in these microscopic views of brain tumors, ranging from common to rare.

Schwannomas are benign tumors that arise in the peripheral nerves and can spread to the brain. They can cause pain and sometimes nerve damage, but are nearly always benign and usually do not grow back after surgery. They’re one of the only tumors whose cells form palisades, which appear as neatly arranged rows, and show areas of denser and looser architecture.

Meningioma tumors are characterized by distinctive pink whorls of cells. They arise in the membranes surrounding the brain and grow slowly. Roughly 90% of meningioma cases are low-grade, but many do grow back and become resistant to radiation. Currently there are no chemotherapies that have proven effective against these tumors.

Metastatic cancer spreads from another part of the body to the brain and is the most common type of brain cancer. Based on the tumor cell patterns and other special tests, neuropathologists can usually determine from where in the body the tumor came. For example, metastatic cancer from the colon tries to form little glands within the brain filled with cellular debris, whereas metastatic cancer from the breast or lung sometimes produces mucus that shows up as bluish-grey material between the cancerous glands.

_{Metastatic brain tumor from colorectal cancer.}

^{Metastatic brain tumor from breast cancer.}

Choroid plexus papillomas form in the choroid plexus, which is the area at the base of the brain where cerebrospinal fluid is made. They present as finger-like structures and are typically low-grade, but can sometimes become aggressive. Even low-grade tumors can be lethal if they block the flow of cerebrospinal fluid, causing excessive pressure in the brain.

Chordomas occur in one out of one million people. The tumor cells form little bubbles and often produce a lot of cartilage-like material, seen as blue-grey areas within the tumor. They form along the spine, invade local structures, and can even destroy the bones at the base of the skull or the spine. Despite surgical resection and radiation, these tumors usually keep growing back.

Glioblastoma is the most common and, unfortunately, the most malignant tumor that starts within the brain itself. Glioblastoma tumor cells spread throughout the brain so that complete surgical removal is not possible. Radiation and chemotherapy are used to slow the spread of the tumor; they do not cure the condition. Roughly 12,000 people are diagnosed with glioblastomas in the United States every year.

Analyzing a biopsy under the microscope is just one way physicians determine diagnosis and prognosis of brain tumors.

“We can achieve great understanding of brain tumors and how to treat them by looking at these tiny patterns and structures on the microscopic level,” says Dr. Horbinski. “Though seemingly behind-the-scenes, pathology is vital for patient treatment, and it is pushing our treatment options forward, one step at a time.”