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Neuropathologist Dr. Julia Keith.

When pathologists examine tissue to look for signs of cancer, it's an extraordinary meeting of art and science 

After 29-year-old Shawn Spooner had his first seizure, he was referred for an MRI, which revealed a mass on his brain stem. In March of 2012, Shawn underwent surgery at Sunnybrook to have the tumour removed, a process that took eight hours. "I tried to stay positive, but there's always that part of your mind that thinks the worst," recalls the project manager in the telecom industry. Doctors discovered there was another, smaller tumour, as well, but its location made it more difficult to remove, and doctors wanted to know more.

That's where Dr. Julia Keith of Sunnybrook's Department of Anatomic Pathology, comes in. One of 40 neuropathologists in Canada, she analyzes tissue samples – like those taken from Shawn's brain – to determine if someone has cancer and what type of cancer it is. There are, after all, hundreds of possibilities. Before she can do this, however, the tissue specimen must be transformed into a tiny piece of "art" affixed between glass.

Photomicrograph of Shawn Spooner's brain tumour
– known as a subependymoma – showing relatively
low cellularity and a nonmalignant appearance.

How does this transformation happen? As soon as a piece of tissue is taken out, it's placed in a plastic container in a protective solution. Next, the label with the patient's information is checked and re-checked and a unique barcode is assigned to each specimen. "Minimizing errors is something that pathology departments take very seriously," explains Dr. Keith. Large samples of the specimen need to be cut by a pathology assistant, and each piece is put in a plastic tray or cassette that's smaller than a matchbox, and is labelled with the patient's barcode.

Once in the trays, various solutions are added to the samples to dehydrate and harden them. Machines that use microwave technology can speed up this process. "We can now get a breast biopsy and in the same day do the processing; whereas, it used to have it sit in solution overnight," explains Dr. Corwyn Rowsell, deputy chief of Anatomic Pathology at Sunnybrook.

Next, a medical lab technologist adds hot paraffin wax to each cassette and places these blocks on trays of ice to allow the wax to harden. Each block is then fed into special machines and another technologist skillfully makes four-micrometre thick slices from the block. The slices are then carefully floated within a water bath, then deftly affixed onto a glass slide.

Some of the slides are then fed through a routine staining machine, while others are left as blank canvases. The reactive compounds in the routine stain (Hematoxylin and Eosin) turn the nucleus of each cell blue, while other structures, like the cell wall and proteins, stain pink. To the naked eye, the stained slide looks like purple fingerprints or ink blots.

Some samples need special stains, however, to identify unique structures, such as the bacteria causing an infection. These stains are prepared by a lab technologist, and are based on Standard Operating Procedures formulas and applied with eyedroppers to the slides. One type of stain is made with real saffron; others have names like "Movat's Pentachrome" and "Gram stain."

Once a slide is stained, it's ready for Dr. Keith to examine under a microscope. In some cases, her trained eye can identify a cancer based on how the cells look, how numerous and spaced the cells are and how many cells are captured in the act of dividing. Says Dr. Keith, "You have to have a good eye and extensive training to interpret the things you see on the slide."

When Dr. Keith needs more details on what she's seeing, she'll order the plain tissue samples to be stained with other compounds – called immunohistochemical stains – to help identify cell and tumour types. Many cancers can spread (metastasize) to the brain or spine, from other sites in the body. "The first step is identifying metastatic disease, but then I want to know: 'Where did this cancer come from?'" explains Dr. Keith. For example, if a "TTF1 stain" stains the nuclei of the tumour cells brown against a blue background, Dr. Keith knows she's seeing a metastatic tumour to the brain, from the lung. Aside from immunohistochemical stains, Dr. Keith might also order genetic tests on a brain tumour (see sidebar).

So what did the slides of the tumour specimen removed from Shawn's brain reveal? From the routinely stained slides, Dr. Keith could tell right away the tumour wasn't usual. Most brain tumours have cells that are chaotically arranged and fast-growing. But in Shawn's case, the blue-stained nuclei of the cells were the same shape and size, and none of the cells were caught in the act of dividing. These traits, and the way the cells were clustered together with some spaces in the background, led Dr. Keith to a subependymoma. "Fortunately, it is one of the most benign brain tumours," she explains.

At Sunnybrook's Odette Cancer Centre, pathologists participate in multidisciplinary cancer conferences. These are regularly scheduled meetings bringing together cancer care professionals from different disciplines – to include pathology, radiology, surgical, radiation and medical oncology, nursing and pharmacy – who discuss and share expertise on the complexities of a treatment plan for a patient, to ensure a co-ordinated approach.

Shawn isn't expected to need chemo or radiation for the remaining tumour. Instead, he goes for an MRI every six months to ensure the tumour hasn't grown.

Watching the tumour samples be cut, processed, embedded in wax and stained, it's easy to forget that each of these tiny samples tells a story. Fortunately, we're increasingly wresting control of these stories, which is why Dr. Keith is also involved in research and meets regularly with neuropathologists across the country and around the world. "The more we learn, the more we can personalize treatment," she says. "Pathology is changing extremely rapidly."


"Genetic studies are featuring more and more in the diagnosis and how we predict how a patient will respond to a certain therapy," says Dr. Julia Keith, who increasingly sends tumour samples to specialized labs for genetic testing. "As pathologists, we need to stay up-to-date in terms of what types of testing are clinically useful and available, and sometimes we need to help propel the development of a certain test."

The shift toward including genetics to help classify tumours means a steep learning curve, which is why it's a key advantage that each pathologist at Sunnybrook has specialized expertise, focusing on diseases affecting a particular organ system. "The breast tumours are interpreted by the breast pathologist, the gynecological cancers are interpreted by the gynepathologist and so on," says Dr. Keith. Likewise, she focuses on diseases affecting the nervous system. "The diseases of the brain are unique. You need a dedicated expert to interpret brain tumours."

This content was produced by The Globe and Mail's advertising department, in consultation with Sunnybrook. The Globe's editorial department was not involved in its creation.

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