Micrometastasis is the term for small collections of cancer cells that have broken away from a primary tumor and traveled to other parts of the body. These clusters, defined as being between 0.2 and 2 millimeters in diameter, are too small to be detected by imaging tests like CT scans or MRIs. They can only be seen when tissue is removed and examined under a microscope.
The concept is similar to seeds scattered from a plant. The primary tumor is the original plant, while the cancer cells are seeds that land in new locations, such as different organs or tissues. These seeds have not yet grown into new tumors, but their presence represents the potential for the cancer to return.
The Process of Micrometastatic Spread
The process begins when cancer cells detach from the original tumor and invade surrounding tissue. From there, they can penetrate the walls of nearby blood vessels or lymphatic channels, a process called intravasation.
Once inside the bloodstream or lymphatic system, these are known as circulating tumor cells (CTCs). Most CTCs do not survive the journey through the body, but some endure by cloaking themselves with platelets to avoid the immune system. If a CTC survives, it must exit the circulation to settle in a new location, a process called extravasation.
The cell adheres to a vessel wall in a distant organ, such as the liver or lungs, and pushes into the new tissue to form a colony. After arriving, these cancer cells can enter a state of dormancy, remaining inactive for months or even years. These dormant cells may later “awaken” and grow into detectable tumors, leading to cancer recurrence.
Detecting Hidden Cancer Cells
Because doctors cannot biopsy every organ, they use targeted methods to sample tissues most likely to harbor these cells, such as the lymph nodes closest to the tumor. One procedure is the sentinel lymph node biopsy. The sentinel node is the first lymph node to which cancer cells are most likely to spread.
Surgeons inject a dye or radioactive substance near the tumor, which travels to this first node, allowing it to be identified and removed for examination. Once a tissue sample is obtained, it is analyzed using advanced methods.
Immunohistochemistry (IHC) is a technique where pathologists apply antibodies designed to bind to proteins on cancer cells. These antibodies are linked to a dye, causing the cancer cells to change color and become visible under a microscope. For even greater sensitivity, molecular testing like reverse transcription-polymerase chain reaction (RT-PCR) can be used. This method detects the genetic material of cancer cells by amplifying messenger RNA (mRNA) unique to the cancer, which can identify a single cancer cell among a million healthy cells.
Impact on Cancer Prognosis and Staging
The discovery of micrometastases provides information about a tumor’s potential to spread, which influences the cancer’s stage and a patient’s long-term outlook. Finding these cells can lead to upstaging, where the cancer is classified as more advanced than previously thought.
Cancer staging systems, like the TNM system, classify the extent of the disease. The presence of micrometastases in a lymph node can change the “N” (node) category, moving a cancer from a localized stage to a more advanced one. This indicates the disease has spread beyond its origin.
The presence of micrometastases also affects a patient’s prognosis. It indicates a higher statistical risk of future recurrence because it confirms the tumor has acquired the ability to travel through the body. While this does not guarantee recurrence, it is an important risk factor that helps guide treatment decisions.
Therapeutic Strategies for Micrometastasis
The goal of treating micrometastasis is to eliminate hidden cancer cells remaining in the body after a tumor is surgically removed. This is done with adjuvant therapy, which is treatment given after surgery to destroy microscopic deposits before they can grow.
Systemic therapies are the main approach because they circulate throughout the body and can reach cancer cells anywhere they have settled. The type of adjuvant therapy depends on the specific cancer and may include one or more of the following:
- Chemotherapy uses drugs to kill rapidly dividing cells.
- Hormone therapy is effective for cancers fueled by hormones, like certain breast and prostate cancers.
- Targeted therapy uses drugs designed to attack specific molecular features on cancer cells.
- Immunotherapy stimulates the patient’s own immune system to recognize and destroy cancer cells.