Understanding Pathology and Staging

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The extent of cancer, what it looks like and where it is will guide diagnosis and treatment.

A number of things must be considered before a doctor can offer treatment options for cancer. The doctor must know how much cancer is in the patient’s body, where it is located, whether it has spread, and the specific type of cells that make up the tumor and how aggressive they are.

The Pathologist

In addition to conducting laboratory tests to diagnose diseases in general, pathologists also conduct specific tests on the cancer to determine a number of factors, including the type of cancer cells, the grade of the cancer, the size of the tumor, the extent the cancer has invaded the surrounding tissue and whether the cancer has spread to lymph nodes and other locations in the body. This information, compiled in a pathology report, provides patients and their medical teams with essential information to help them determine the best treatment. The pathologist first looks at the tissue with the naked eye in a “gross examination.” Its appearance and characteristics, such as size, weight, color and texture, are recorded.

If an entire tumor or lesion has been removed, it is microscopically measured from the edge of the malignancy to the edge of the removed tissue, which should include healthy tissue. If cancer cells are found at the edge, that is considered a positive margin, suggesting that more cancer cells could remain in the body. This means that more surgery or other treatments might be needed to try to remove or kill any remaining cancer cells. A negative or clean margin means there are no cancer cells found at the edge of the removed tissue.

Once removed, the specimen is cut into thin slices by the pathologist for further testing. The pathologist examines the tissue under a microscope, but other techniques are sometimes used to identify factors involved in the abnormal growth of cells, including fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) or other molecular tests to identify mutated genes that might help to drive the cancer. Many tumor characteristics identified by these tests can be important in choosing the right treatment.

As the technology to examine cells has become more advanced, pathology offers more extensive information about which treatments will be most effective.

Patients should ask their doctors about the cancer’s pathology to learn as much as possible about why a certain treatment is recommended and how it will work against the cancer.

If the patient’s cancer is very rare or if the doctor thinks the pathologist’s diagnosis is inconsistent with the patient’s symptoms and other test results, a second opinion might be appropriate.

Grading Systems

The pathologist provides a number of evaluative elements that can help patients understand their tumors. A tumor’s grade describes how abnormal the cancer cells appear under the microscope.

Factors that go into deciding the grade vary, but usually include the size and shape of the cell’s nucleus, the proportion of cancer cells that are dividing and the patterns the cells form as they join. If many cells are dividing, it can be a sign that the cancer is aggressive.

Cancer cells that look more like normal cells usually grow and multiply slowly and are described as being low grade, well differentiated or grade 1. Conversely, cancers that do not resemble normal tissues are called high grade, poorly differentiated or grade 3 or 4. The attributes are combined into an overall tumor grade that ranges from 1 to 4 depending on the cancer type.

Grading systems vary depending on if the cancer is a solid or liquid tumor, and what type of cancer has been identified. For example, the grading system for prostate cancer ranges from 2 to 10. Patients should ask their doctors what factors go into grading the tumor and the scale used.

Regardless of the system used, lower numbers signify less aggressive cancers, and higher numbers more rapid growth. Tumor grade is an important indicator of prognosis in some cancers, such as brain, breast and prostate, as well as lymphoma and soft-tissue sarcoma.

Staging Systems

Many cancers are also staged from 0 to 4, with 4 usually indicating that the cancer is metastatic. Solid and liquid tumors are staged differently, and the staging of certain cancer types may differ. So, patients should try to understand how their cancer is staged and how important this information is for their cancer type.

Staging for most cancers is based on the following:

  • Location and size of the primary tumor.
  • The number of tumors and whether the cancer has spread to nearby organs and tissues, including the lymph nodes.
  • Whether the cancer has spread (metastasized) to distant organs or tissues.

For some cancers, such as bone and soft- tissue sarcomas, the grade is considered when the cancer is staged. In addition to what is contained in the pathology report, data used for staging are gathered from physical examinations and imaging tests, such as X-rays, computed tomography (CT) scans, positive emission tomography (PET) and bone scans and magnetic resonance imaging (MRI) scans.

TNM staging uses three characteristics of the cancer. The T refers to the primary tumor (the place where the cancer began); the N refers to the level, if any, of lymph node involvement; and the M refers to the presence or absence of metastasis. The meaning of these letters and numbers might vary for different types of cancer; some cancers might not have N3 as a category, and in other cancers, the classifications might have subcategories, such as T3a or T3b. Patients should ask their doctors about the staging system for their cancer.

Once these factors are known, an overall number is assigned. Patients who are treated and then experience a recurrence might have their cancer restaged. A restaged cancer often is indicated by inclusion of the letter “R.”

Newer chromosome tests and the analysis of multiple genes at a time (known as gene pro- filing) could subclassify the cancer and help determine prognosis and individual treatment. That's why the 8th edition of the American Joint Committee on Cancer staging system integrates grade and biomarker/molecular data, as well as anatomical indices.

Besides stage and grade, the patient’s cancer type, treatment and health influence prognosis. But understanding what is the cancer’s stage and grade mean can help patients and their care teams choose the best course of action.