CIENCIASMEDICASNEWS: Sentinel Lymph Node Biopsy

Sentinel Lymph Node Biopsy - National Cancer Institute

National Cancer Institute at the National Institutes of Health

Sentinel Lymph Node Biopsy

Key Points

A sentinel lymph node is the first lymph node(s) to which cancer cells are most likely to spread from a primary tumor.
A sentinel lymph node biopsy (SLNB) can be used to help determine the extent, or stage, of cancer in the body.
Because SLNBs involve less extensive surgery and the removal of fewer lymph nodes than standard lymph node surgery, the potential for adverse effects, or harms, is lower.

What are lymph nodes?
Lymph nodes are small round organs that are part of the body’s lymphatic system. They are found widely throughout the body and are connected to one another by lymph vessels. Groups of lymph nodes are located in the neck, underarms, chest, abdomen, and groin. A clear fluid called lymph flows through lymph vessels and lymph nodes.

Anatomy of the lymphatic system, showing the lymph vessels and lymph organs, including lymph nodes, tonsils, thymus, spleen, and bone marrow. One inset shows the structure of a lymph node and the lymph vessels, with arrows showing how lymph and immune cells called lymphocytes move into and out of the lymph node. Another inset shows a close-up of bone marrow.
Lymph originates from a fluid, known as interstitial fluid, that has diffused, or “leaked,” out of small blood vessels called capillaries. This fluid contains many substances, including blood plasma, proteins, glucose, and oxygen. It bathes most of the body’s cells, providing them with the oxygen and nutrients they need for growth and survival. Interstitial fluid also picks up waste products from cells as well as other materials, such as bacteria and viruses, to help remove them from the body’s tissues. Interstitial fluid eventually collects in lymph vessels, where it becomes known as lymph. Lymph flows through the body’s lymph vessels to reach two large ducts at the base of the neck, where it is emptied into the bloodstream.
Lymph nodes are important parts of the body’s immune system. They contain B lymphocytes, T lymphocytes, and other types of immune system cells. These cells monitor lymph for the presence of “foreign” substances, such as bacteria and viruses. If a foreign substance is detected, some of the cells will become activated and an immune response will be triggered.
Lymph nodes are also important in helping to determine whether cancer cells have developed the ability to spread to other parts of the body. Many types of cancer spread through the lymphatic system, and one of the earliest sites of spread for these cancers is nearby lymph nodes.
What is a sentinel lymph node?
A sentinel lymph node is defined as the first lymph node to which cancer cells are most likely to spread from a primary tumor. Sometimes, there can be more than one sentinel lymph node.
What is a sentinel lymph node biopsy?
A sentinel lymph node biopsy (SLNB) is a procedure in which the sentinel lymph node is identified, removed, and examined to determine whether cancer cells are present.
A negative SLNB result suggests that cancer has not developed the ability to spread to nearby lymph nodes or other organs. A positive SLNB result indicates that cancer is present in the sentinel lymph node and may be present in other nearby lymph nodes (called regional lymph nodes) and, possibly, other organs. This information can help a doctor determine the stage of the cancer (extent of the disease within the body) and develop an appropriate treatment plan.
What happens during an SLNB?
A surgeon injects a radioactive substance, a blue dye, or both near the tumor to locate the position of the sentinel lymph node. The surgeon then uses a device that detects radioactivity to find the sentinel node or looks for lymph nodes that are stained with the blue dye. Once the sentinel lymph node is located, the surgeon makes a small incision (about 1/2 inch) in the overlying skin and removes the node.
The sentinel node is then checked for the presence of cancer cells by a pathologist. If cancer is found, the surgeon may remove additional lymph nodes, either during the same biopsy procedure or during a follow-up surgical procedure. SLNBs may be done on an outpatient basis or may require a short stay in the hospital.
SLNB is usually done at the same time the primary tumor is removed. However, the procedure can also be done either before or after removal of the tumor.
What are the benefits of SLNB?
In addition to helping doctors stage cancers and estimate the risk that tumor cells have developed the ability to spread to other parts of the body, SLNB may help some patients avoid more extensive lymph node surgery. Removing additional nearby lymph nodes to look for cancer cells may not be necessary if the sentinel node is negative for cancer. All lymph node surgery can have adverse effects, and some of these effects may be reduced or avoided if fewer lymph nodes are removed. The potential adverse effects of lymph node surgery include the following:
- Lymphedema, or tissue swelling. During SLNB or more extensive lymph node surgery, lymph vessels leading to and from the sentinel node or group of nodes are cut, thereby disrupting the normal flow of lymph through the affected area. This disruption may lead to an abnormal buildup of lymph fluid. In addition to swelling, patients with lymphedema may experience pain or discomfort in the affected area, and the overlying skin may become thickened or hard. In the case of extensive lymph node surgery in an armpit or groin, the swelling may affect an entire arm or leg. In addition, there is an increased risk of infection in the affected area or limb. Very rarely, chronic lymphedema due to extensive lymph node removal may cause a cancer of the lymphatic vessels called lymphangiosarcoma.
- Seroma, or the buildup of lymph fluid at the site of the surgery.
- Numbness, tingling, or pain at the site of the surgery.
- Difficulty moving the affected body part.
Is SLNB associated with other harms?
SLNB, like other surgical procedures, can cause short-term pain, swelling, and bruising at the surgical site and increase the risk of infection. In addition, some patients may have skin or allergic reactions to the blue dye used in SLNB. Another potential harm is a false-negative biopsy result—that is, cancer cells are not seen in the sentinel lymph node although they are present and may have already spread to other regional lymph nodes or other parts of the body. A false-negative biopsy result gives the patient and the doctor a false sense of security about the extent of cancer in the patient’s body.
Is SLNB used to help stage all types of cancer?
No. SLNB is most commonly used to help stage breast cancer and melanoma. However, it is being studied with other cancer types, including colorectal cancer, gastric cancer, esophageal cancer, head and neck cancer, thyroid cancer, and non-small cell lung cancer (1).
What has research shown about the use of SLNB in breast cancer?
Breast cancer cells are most likely to spread first to lymph nodes located in the axilla, or armpit area, next to the affected breast. However, in breast cancers close to the center of the chest (near the breastbone), cancer cells may spread first to lymph nodes inside the chest (under the breastbone) before they can be detected in the axilla.
The number of lymph nodes in the axilla varies from person to person but usually ranges from 20 to 40. Historically, removal of these lymph nodes (in an operation called axillary lymph node dissection, or ALND) was done for two reasons: to help stage breast cancer and to help prevent a regional recurrence of the disease. (Regional recurrence of breast cancer occurs when breast cancer cells that have migrated to nearby lymph nodes give rise to a new tumor.)
Because removing multiple lymph nodes at the same time has been associated with adverse effects, the possibility that SLNB alone might be sufficient for staging breast cancer in women who have no clinical signs of axillary lymph node metastasis, such as swollen or “matted” (clumped or stuck together) nodes, was investigated.

Sentinel lymph node biopsy of the breast. A radioactive substance and/or blue dye is injected near the tumor (first panel). The injected material is located visually and/or with a device that detects radioactivity (middle panel). The sentinel node(s) (the first lymph node(s) to take up the material) is (are) removed and checked for cancer cells (last panel).
In a phase III trial involving 5,611 women with breast cancer and no clinical signs of axillary metastasis, researchers from the National Surgical Adjuvant Breast and Bowel Project, which is a National Cancer Institute (NCI) clinical trials cooperative group, randomly assigned participants to receive SLNB alone or SLNB plus ALND (2). The women in the two groups whose sentinel lymph node(s) were negative for cancer (a total of 3,989 women) were then followed for an average of 8 years. Most of the women (87.5 percent) had a lumpectomy, and the rest had a mastectomy. Nearly 88 percent of the women also received adjuvant systemic therapy (chemotherapy, hormonal therapy, or both), and 82 percent had external-beam radiation therapy to the affected breast.
The researchers found no differences in overall survival and disease-free survival between the two groups of women. Based on these results, it was concluded that ALND might not be necessary for women with clinically negative axillary lymph nodes and a negative SLNB whose breast cancer is treated with surgery, adjuvant systemic therapy, and external-beam radiation therapy.
Subsequently, the American College of Surgeons Oncology Group, which is another NCI clinical trials cooperative group, reported findings from an additional phase III clinical trial, this one testing whether women with a positive sentinel lymph node but no clinical evidence of axillary lymph node metastasis could be safely treated with tumor removal and no further lymph node surgery other than the SLNB (3). In this trial, 891 women were randomly assigned to SLNB only or ALND after SLNB (3). All of the women were treated with lumpectomy. More than 95 percent of them also received adjuvant systemic therapy (chemotherapy, hormone therapy, or both), and about 90 percent received external-beam radiation therapy to the affected breast.
When the results of this trial were reported, the patients had been followed for a median of 6.3 years. The two groups of women had similar 5-year overall survival (92.5 percent in the SLNB-only group versus 91.8 percent in the SLNB plus ALND group) and 5-year disease-free survival (83.9 percent in the SLNB-only group and 82.2 percent in the SLNB plus ALND group). The researchers concluded that SLNB alone is safe and does not affect the survival of women who have sentinel lymph node metastasis but no clinical signs of other lymph node involvement and whose breast cancer is treated with surgery, systemic therapy, and external-beam radiation therapy. The excellent outcome in this trial for women treated with SLNB without ALND is likely due, at least in part, to the ability of local radiation therapy and modern systemic treatments to effectively treat breast cancer cells that may have spread to other axillary lymph nodes besides the sentinel node or to other parts of the body.
What has research shown about the use of SLNB in melanoma?
Researchers have investigated whether patients with melanoma whose sentinel lymph node is negative for cancer and who have no clinical signs of other lymph node involvement can also be spared more extensive lymph node surgery at the time of primary tumor removal. A meta-analysis of 71 studies that involved data from 25,240 patients suggests that the answer to this question is “yes.” This meta-analysis found that the risk of regional lymph node recurrence in patients with a negative SLNB was 5 percent or less (4).

Sentinel lymph node biopsy in a patient with melanoma. A radioactive substance and/or blue dye is injected near the tumor (first panel). The injected material is located visually and/or with a device that detects radioactivity (middle panel). The sentinel node(s) (the first lymph node(s) to take up the material) is (are) removed and checked for cancer cells (last panel). Sentinel lymph node biopsy can be done before or after the tumor is removed.
Another question posed by researchers is whether SLNB plus the removal of the remaining regional lymph nodes (called completion lymph node dissection, or CLND) if the sentinel lymph node is positive for cancer has a therapeutic benefit for melanoma patients in terms of disease-free survival and melanoma-specific survival (length of time until death from melanoma). To address this question, NCI, the National Institutes of Health, and the John Wayne Cancer Institute are sponsoring a large phase III clinical trial called the Multicenter Selective Lymphadenectomy Trial II, or MSLT-II. In this trial, more than 1,900 patients with positive sentinel lymph nodes but no clinical evidence of other lymph node involvement are being randomly assigned to immediate CLND or regular ultrasound examination of the remaining regional lymph nodes and CLND if signs of additional lymph node metastasis appear. The patients in this trial will be followed for 10 years.
Where can people find more information about clinical trials that are studying SLNB?
Information about current clinical trials that are studying SLNB in cancer is available on NCI’s Web site. This information can be accessed at Current Clinical Trials of SLNB or by using the clinical trials search form.
Alternatively, contact NCI’s Cancer Information Service (CIS) for information about clinical trials of SLNB. (See CIS contact information below.)

Selected References

Chen SL, Iddings DM, Scheri RP, Bilchik AJ. Lymphatic mapping and sentinel node analysis: current concepts and applications. CA: A Cancer Journal for Clinicians 2006; 56(5):292–309. [PubMed Abstract]
Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncology 2010; 11(10):927–933. [PubMed Abstract]
Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA: The Journal of the American Medical Association 2011; 305(6):569–575. [PubMed Abstract]
Valsecchi ME, Silbermins D, de Rosa N, Wong SL, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma: a meta-analysis. Journal of Clinical Oncology 2011; 29(11):1479–1487. [PubMed Abstract]

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