Definition

Tumor grade refers to systems for determining the degree of malignancy of a tumor and classifies cells in terms of abnormal characteristics of the tumor cells (it is differentiated from cancer staging which refers to the severity and extent of the spread of the disease). It is determined by a pathologist from biopsied tumor tissue, as well as other characteristics of the tumor. The National Cancer Institute “Pathology Reports” (http://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/pathology-reports-fact-sheet) describes the information found in pathology reports.

Oncologists use a tumor grading system to help determine prognosis and treatment options. The specific characteristics differ in reference to different tumor types. Tumor types refer to the cells from which they developed (e.g., astrocytomas develop from unregulated growth of astrocytes). Other brain tumor types are not graded but classified by how abnormal the cancer cells and milieu looks and how likely the tumor will grow or disseminate (Fig. 1).

Tumor Grade, Fig. 1
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Malignant tumor (Courtesy Michael Fisher, MD, Peter C. Phillips, MD. The Children’s Hospital of Philadelphia)

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Current Knowledge

The tumor grading used for the most common tumors – gliomas – comes from the American Joint Commission on Cancer. In reference to gliomas, it can be generally stated that tumors are classified as one of the four grades (Cancer 2002):

  1. 1.

    Low grade I, in which case the tumor cells remain well differentiated and without other signs of abnormality in cell nuclei or tissue structure. The tumor cells grow slowly, rarely grow into the surrounding tissue, and may be gross totally resected.

  2. 2.

    Low-grade II, considered moderately differentiated but still benign. Grade II tumors have a greater chance of de-differentiation and transformation into a more malignant tumor and may have spread into the surrounding tissue.

  3. 3.

    Anaplastic (grade III), the tumor cells are poorly differentiated, the tumor has likely spread into the surrounding tissue, and the tumor is malignant.

  4. 4.

    High grade, undifferentiated, and highly malignant and aggressive (e.g., glioblastoma multiforme are always considered grade IV). At this stage, tumors are very difficult to treat.

The histologic characteristics that are considered in tumor grading include the degree of pleomorphism, nuclear atypia, endothelial proliferation, mitotic rates, and focal or superpalisading necrosis. A more general classification is (1) well differentiated and low grade, (2) moderately differentiated and intermediate, (3) poorly differentiated and high grade, and (4) undifferentiated and high grade.

Although tumor histology itself does not appear to influence the severity or type of cognitive impairment (Kayl and Meyers 2003) (aside from the location of the tumor), tumor grade is associated with the severity of neuropsychological deficit. This is because higher grade tumors grow more aggressively, are larger, and thus are more disruptive of neural connections. A neuropsychological study that compared cognitive impairments resulting from tumors versus stroke (cases individually matched by location of lesion, with tumor lesions at least as large or larger than the stroke lesion) shows that tumors tend to cause less impairment, and tumors may cause less “focal” deficit than strokes (Anderson et al. 1990).