• Cancer Staging and Grading

    Once a malignancy has been diagnosed, the doctor will determine if it has spread beyond the original site. The cancer will be assigned a stage and grade which will help determine your prognosis and treatment. Advanced or late stage cancers for example, are associated with an unfavorable prognosis and are primarily treated with chemotherapy. Early stage tumors, by comparison, are usually associated with a favorable prognosis and are primarily treated with surgery, although chemo- and radiation therapy are sometimes also used to increase the likelihood of a cure.
    A cancer's stage is generally based on 4 pieces of information about the original tumor:

    The TNM Classification System

    Although newer staging protocols have recently been developed for many cancers, the original TNM system is still useful to demonstrate the concept of staging. The TNM classification system was developed as a tool for doctors to stage different types of cancer based on certain standard criteria. In this system, T stands for the primary tumor, N stands for lymph nodes, and M stands for metastasis.
    T refers to the tumor size: the higher the number, the larger the tumor.
    • TX (presence of primary tumor cannot be assessed)
    • T0 (no evidence of primary tumor)
    • Tis (carcinoma in situ)
    • T1 (small tumor)
    • T2, T3 (medium-sized tumor)
    • T4 (large tumor)
    While the designations T1 through T4 correspond to specific tumor sizes, their exact definitions will vary depending on the type and nature of cancer being diagnosed. For example, in non-small cell lung cancer, a T1 tumor is defined as being less than 3 centimeters (cm) in diameter, but in thyroid cancer, a T1 tumor is less than 1 cm in diameter.
    N denotes whether the regional lymph nodes (the group of lymph nodes closest to the site of the primary tumor) contain cancer. The status of the nodes is assigned a number to indicate if the tumor has spread to the local lymph nodes, and the extent of lymph node involvement:
    • NX (regional lymph nodes cannot be assessed)
    • N0 (no regional lymph node involvement)
    • N1, N2, N3 (increasing involvement of regional lymph nodes)
    As with the T symbols, the designations N1 through N3 will differ depending on the particular type of cancer. For some types of cancer, N1 is the only level of regional metastasis. Others will use all 3 N levels. See the Focus on box below to learn more about the lymphatic system.

    Focus Box: Metastasis and the Lymphatic System
    The lymphatic system is a network of channels that in many respects resembles a sewer system. It drains excess fluid containing dead or damaged cells, other debris, and toxins and bacteria from the tissues back into the blood vessels. The channels are periodically interrupted by clusters of lymph nodes found throughout the body, particularly in the neck, torso, axillae (armpits) and groin. As it passes through these lymph nodes, the lymph fluid is exposed to numerous specialized cells of the immune system (lymphocytes) that clear the fluid of the “trash”. Cancer cells leaving the site of a primary tumor quickly encounter a lymph channel, which carries them to the nearest lymph node cluster. For example, as breast cancer spreads, the cells are collected by the lymph channels in the breast and are taken to the axillary lymph node on the same side. This is why surgeons routinely remove many of these lymph nodes in that location to see if the cancer has already spread. Eventually, the cancer cells can reach the bloodstream where they may be transported to distant sites throughout the body.
    M indicates the absence or presence of distant metastases (spread of cancer to other parts of body via the bloodstream):
    • MX (presence of distant metastasis cannot be assessed)
    • M0 (no distant metastasis)
    • M1 (distant metastasis present)
    A letter is sometimes added to the M to show the areas involved. P, for instance, would indicate pulmonary, meaning that the cancer had spread to the lungs.

    Putting T, N, M Together

    Oncologists may combine the T, N, and M classification to determine a cancer’s stage. For example, in breast cancer, a T1, N0, M0 cancer (small tumor, no nodal involvement, no distant metastasis) is considered a stage I tumor, while a T2, N1, M0 cancer (medium sized tumor, regional lymph node involvement, no distant metastasis) is considered a stage II tumor. Most cancers are staged as 0-IV or I-IV.
    Some carcinoma in situ tumors are stage 0. Stage I tumors are relatively small and have not spread to the lymph nodes or metastasized. Conversely, Stage IV tumors are relatively large, have spread to the regional lymph nodes, and have metastasized to distant sites in the body. The images below illustrate these various stages.
    Image correction for cancer coe
    Image 1: Stage I and Stage II Breast Cancer

    Image correction for cancer coe
    Image 2: Stage III and IV (Metastatic) Breast Cancer

    The TNM system has undergone numerous revisions as more is learned about how various cancers behave in the body. In addition, brain tumors and blood (hematologic) cancers, such as the leukemias, require staging systems that reflect their unique nature. InDepth Reports have staging and other information specific to the most common cancers.

    Grading Tumors

    A tumor’s grade describes how closely cancer cells resemble their normal counterparts. This is also referred to as cancer cells’ degree of differentiation. (See the Focus box below for a brief discussion of the importance of cell differentiation in cancer.) Some cancer cells are well differentiated and thus resemble normal cells, while others are poorly differentiated and bear little resemblance to normal cells. In general, the more poorly differentiated the cancer cells, the worse the prognosis. In one system, the symbols used to classify tumor grade are:
    • GX (grade not assessable)
    • G1 (well differentiated)
    • G2 (moderately differentiated)
    • G3 (poorly differentiated)
    • G4 (undifferentiated); in other words, extremely poorly differentiated and bearing little resemblance to the tissue in which it arose)
    Focus Box: Cell Differentiation and Tumor Grading
    Dedifferentiation is a process whereby cancer cells lose the distinctive cellular features that are characteristic of the tissues in which they arose. The better differentiated a cancer is, the more it resembles its tissue of origin and the more likely it is that the tumor will be less aggressive. The more poorly differentiated a cancer is, the less it resembles its tissue of origin, and the more likely it is to be aggressive. In poorly differentiated prostate cancer for example, doctors would find it difficult to identify the cancer cells as coming from the prostate gland if it were not for knowing the site in which the primary tumor is found and without relying on special stains that identify cellular markers found in prostate tissue. Additionally, poorly differentiated cells grow rapidly and without restraint, whereas well-differentiated cells (which closely resemble their tissue of origin) are either unable to proliferate or proliferate at a very slow rate. Aggressive cancers are often characterized by poorly differentiated cells, while less aggressive cancers tend to contain moderately- or well-differentiated cells.


    Cancer diagnosis. Merck Manual Professional version website. Available at: http://www.merckmanuals.com/professional/hematology-and-oncology/overview-of-cancer/cancer-diagnosis. Updated July 2013. Accessed December 27, 2016.

    Cancer staging. American Cancer Society website. Available at: http://www.cancer.org/treatment/understandingyourdiagnosis/staging. Updated March 25, 2015. Accessed December 27, 2016.

    Staging. National Cancer Institute website. Available at: http://www.cancer.gov/cancertopics/diagnosis-staging/staging. Updated March 9, 2015. Accessed December 27, 2016.

    Tumor grade. National Cancer Institute website. Available at: http://www.cancer.gov/cancertopics/diagnosis-staging/prognosis/tumor-grade-fact-sheet. Updated May 3, 2013. Accessed December 27, 2016.

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