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But in recent years, research has led to the development of tests that can identify specific genes and proteins involved in the tumor's growth. These specific tests can help to more accurately identify the type of cancer and may provide clues to the best treatment for that cancer type.
"Research over the last 20 years has moved us from simple microscopic examination to the identification of specific genetic defects that contribute to cancer initiation and progression," says Zutter, who conducts research on the role of proteins called "integrins" in cancer progression and metastasis.
One of the first major steps in this new era of pathology came with the development of antibodies that recognize specific cell markers in the patient's tissue, Zutter notes. The techniques that utilize antibodies for diagnosis, immunohistochemistry and flow cytometric analysis, are particularly critical in the field of hematopathology for categorizing lymphomas as either "T" or "B" cell types, which is an important factor in selecting the appropriate treatment.
More recently, as specific genetic and chromosomal abnormalities have been identified, genetic markers have been incorporated into the diagnostic process. Certain lymphomas and leukemias can now be identified by looking for chromosomal translocations or rearrangments between pieces of two different chromosomes.
Because of their usefulness as diagnostic and prognostic factors, both immunohistochemistry and genetic techniques are now part of the set of pathology tools and have become "routine, standard of care" for many cancers, Zutter says.
In addition to identifying the type of cancer a patient has, pathologists also determine the tumor's "grade," which indicates how aggressive the tumor might be. To do this, pathologists examine the size and shape of the cell's nucleus, the number of cells that appear to be dividing, and the patterns the cells form.
"We look at the growth rate of the tumor in several manners," says David Page, M.D., professor of Pathology and Preventive Medicine. "We look at the atypicality of the nuclei (of the cells), and that gives us extra information about the possibility of metastasis and malignant outcome."
If the cancer cells appear relatively normal and are dividing slowly, the cancer is considered "low grade," "well differentiated," or "grade 1." If many of the cells appear to be dividing, which indicates that the cancer may be more aggressive, the cancer is called "high grade," "poorly differentiated," or "grade 3 or 4."
The grading systems are different for different types of cancer. Some, like prostate cancer, are graded on a wider scale ranging from 2 to 10. Generally, the lower the grade, the less aggressive the cancer.
Pathologists also play an important role in cancer "staging," which describes the extent of the cancer and provides clues about the appropriate treatment and the individual's prognosis.
Like the grading systems, systems for staging cancer also vary for different types of cancer. However, most systems take into account the location of the tumor, tumor size and number of tumors, lymph node involvement, cell type and tumor grade, and presence or absence of metastasis (spread to distant tissues).
The most well-known staging system is the TNM system. The "T" refers to the size and extent of the primary tumor; the "N" signifies lymph node involvement; and the "M" indicates spread to distant parts of the body. A number is added to each letter to indicate the extent of disease.
"The pathologist is usually involved in evaluating the 'T' and the 'N,'" says Page, "while the 'M' is more and more determined with clinical imaging, like CT and MRI scans," features added in the recent Collaborative Staging System (see sidebar).
These factors are then combined to determine an overall "stage," which can range from "0" to "IV" with "0" being an early stage cancer (carcinoma in situ) and "IV" being advanced cancer that has spread to distant areas of the body.
Staging provides information about the patient's prognosis and helps guide treatment. And as new diagnostic and predictive markers are discovered, staging systems will evolve to incorporate that new knowledge.
Accurately staging a cancer involves input from many areas– clinicians, radiologists and pathologists.
"The pathologist provides the basic diagnosis, but it needs to fit into the clinical setting. It's not made in a total vacuum," says Page. "Therefore, we work carefully with clinicians about how the information intersects."
This interaction between clinician and pathologist is critical, especially when the diagnosis is not straightforward, as in Marcy Thomas' case.
"A clinician is only as good as their pathologist," says Greer, who has continued to care for Thomas since her initial diagnosis. "The oncologist may be on the 'front lines'...but everything hinges on the pathology."
Since there are over 30 types of lymphoma, determining the specific type was key to deciding how to treat Thomas. Fortunately, Greer says, Vanderbilt has one of the world's experts in lymphoma classification in Collins – one of the originators of the "Lukes-Collins" classification system for lymphoma, an important component of the evolution of lymphoma classification systems.
And it was that answer from the behind-the-scenes player that gave her the information she needed to go forward.
"It was the only way I could make an informed decision," Thomas says. "I think this is important for people who are diagnosed and may have something that doesn't present forthrightly, as mine didn't. You have to have all the information at your disposal." 
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