Tumor Grade

*Tumor grade facts medical author: Melissa Conrad Stöppler, MD

• Tumor grade is a classification system based on the appearance of tumor cells under the microscope.
• Cancer cells that are described as low-grade (grade 1) have an appearance similar to normal cells.
• High-grade (grade 3) cancer cells appear distinctly abnormal under the microscope.
• Low-grade tumors are often referred to as well-differentiated, while high-grade tumors are called poorly differentiated or undifferentiated.
• Typically, high-grade tumors are more likely to grow and spread faster than low-grade tumors.
• Cancer is usually graded on a scale of 1-3, with 3 being the highest grade. Sometimes, a grade of 4 is used to refer to undifferentiated cancers, which do not resemble any type of normal tissue.
• Tumor grade is different from stage, which refers to the extent to which a cancer has spread in the body.

Tumor grade is the description of a tumor based on how abnormal the tumor cells and the tumor tissue look under a microscope. It is an indicator of how quickly a tumor is likely to grow and spread. If the cells of the tumor and the organization of the tumor's tissue are close to those of normal cells and tissue, the tumor is called "well-differentiated." These tumors tend to grow and spread at a slower rate than tumors that are "undifferentiated" or "poorly differentiated," which have abnormal-looking cells and may lack normal tissue structures. Based on these and other differences in microscopic appearance, doctors assign a numerical "grade" to most cancers. The factors used to determine tumor grade can vary between different types of cancer.

Tumor grade is not the same as the stage of a cancer. Cancer stage refers to the size and/or extent (reach) of the original (primary) tumor and whether or not cancer cells have spread in the body. Cancer stage is based on factors such as the location of the primary tumor, tumor size, regional lymph node involvement (the spread of cancer to nearby lymph nodes), and the number of tumors present.

If a tumor is suspected to be malignant, a doctor removes all or part of it during a procedure called a biopsy. A pathologist (a doctor who identifies diseases by studying cells and tissues under a microscope) then examines the biopsied tissue to determine whether the tumor is benign or malignant. The pathologist also determines the tumor's grade and identifies other characteristics of the tumor.

Grading systems differ depending on the type of cancer. In general, tumors are graded as 1, 2, 3, or 4, depending on the amount of abnormality. In Grade 1 tumors, the tumor cells and the organization of the tumor tissue appear close to normal. These tumors tend to grow and spread slowly. In contrast, the cells and tissue of Grade 3 and Grade 4 tumors do not look like normal cells and tissue. Grade 3 and Grade 4 tumors tend to grow rapidly and spread faster than tumors with a lower grade.

If a grading system for a tumor type is not specified, the following system is generally used (1):

• GX: Grade cannot be assessed (undetermined grade)
• G1: Well differentiated (low grade)
• G2: Moderately differentiated (intermediate grade)
• G3: Poorly differentiated (high grade)
• G4: Undifferentiated (high grade)

Breast and prostate cancers are the most common types of cancer that have their own grading systems.

Breast cancer. Doctors most often use the Nottingham grading system (also called the Elston-Ellis modification of the Scarff-Bloom-Richardson grading system) for breast cancer. This system grades breast tumors based on the following features:

• Tubule formation: how much of the tumor tissue has normal breast (milk) duct structures
• Nuclear grade: an evaluation of the size and shape of the nucleus in the tumor cells
• Mitotic rate: how many dividing cells are present, which is a measure of how fast the tumor cells are growing and dividing

Each of the categories gets a score between 1 and 3; a score of "1" means the cells and tumor tissue look the most like normal cells and tissue, and a score of "3" means the cells and tissue look the most abnormal. The scores for the three categories are then added, yielding a total score of 3 to 9. Three grades are possible:

• Total score = 3-5: G1 (Low grade or well differentiated)
• Total score = 6-7: G2 (Intermediate grade or moderately differentiated)
• Total score = 8-9: G3 (High grade or poorly differentiated)

Prostate cancer. The Gleason scoring system is used to grade prostate cancer (1). The Gleason score is based on biopsy samples taken from the prostate. The pathologist checks the samples to see how similar the tumor tissue looks to normal prostate tissue. Both a primary and a secondary pattern of tissue organization are identified. The primary pattern represents the most common tissue pattern seen in the tumor, and the secondary pattern represents the next most common pattern. Each pattern is given a grade from 1 to 5, with 1 looking the most like normal prostate tissue and 5 looking the most abnormal. The two grades are then added to give a Gleason score. The American Joint Committee on Cancer recommends grouping Gleason scores into the following categories (1):

• Gleason X: Gleason score cannot be determined
• Gleason 2-6: The tumor tissue is well differentiated
• Gleason 7: The tumor tissue is moderately differentiated
• Gleason 8-10: The tumor tissue is poorly differentiated or undifferentiated

Doctors use tumor grade and other factors, such as cancer stage and a patient's age and general health, to develop a treatment plan and to determine a patient's prognosis (the likely outcome or course of a disease; the chance of recovery or recurrence). Generally, a lower grade indicates a better prognosis. A higher-grade cancer may grow and spread more quickly and may require immediate or more aggressive treatment.

The importance of tumor grade in planning treatment and determining a patient's prognosis is greater for certain types of cancer, such as soft tissue sarcoma, primary brain tumors, and breast and prostate cancer.

Patients should talk with their doctor for more information about tumor grade and how it relates to their treatment and prognosis.