The sentinel lymph node biopsy technique

 
The sentinel lymph node biopsy is a staging technique for invasive cancer, and also provides useful information to guide subsequent therapies. However, it should be noted that not all clinics use the technique. It is the sort of procedure that may be called for in certain situations. Typically, it would be used in an ‘early-stage breast cancer‘ situation where mammography makes it pretty clear any potentially malignant cells are still confined to the breast ducts. In that sense it is really a technique which would be most applicable in either stage 0 or stage 1 breast cancers.

 

This page still has some great information on sentinel lymph node biopsy, however, we have created a newer version of this page with more up-to-date information.

 

 

Negative Sentinel lymph node generally means that other axillary nodes (underarm lymph nodes) are cancer free

 
The basic concept is that the sentinel lymph node is the first to receive lymphatic drainage or lymph fluid from a malignant tumor that has metastasized (or spread). Therefore, a negative status for the sentinel lymph node can just about guarantee that the other axillary lymph nodes are also clear. This is a very good thing, because axillary lymph node dissection (either for biopsy study or removal of potentially malignant axillary – i.e. around the armpit) nodes can result in many complications such as seroma, lymphedema, arm paresthesia and pain. Furthermore, a major disruption in the normal lymphatic flow can have an adverse effect on gains from previous interventions such as breast surgery or radiation therapy.
 

 

How is a sentinel lymph node biopsy performed?

 
The SLN technique involves the injection into the breast tissue of two different substances: a low radioactive colloid (usually a radioactive technetium molecule) and a blue dye agent (isosulfan blue). With the dye, the sentinel lymph node is stained with the blue color, or found in association with a blue-stained lymphatic channel. When the surgery is about to start, the surgeon needs to find where the radio-labelled lymph nodes are. In order to do this, the surgeon holds a ‘pen-like‘ geiger counter and passes this along the skin. The device will click very rapidly when a ‘radio-active‘ sentinel lymph node is discovered. The spot will be marked with a pen and the node is surgically removed with an excisional biopsy.

In interpreting the results, the pathologist will cross reference a number of different indicators. He/she will look for any node with ‘ex-vivo‘ counts of greater than 3 to 4 times the normal axillary basin count. ‘Ex vivo‘ means the procedure is happening ‘outside of an organism‘. This means that a sample of blood cells are taken from the patient, combined with the dye or colloid, and injected back into the patient. The injected substance is then taken up by the lymphatic system and the patient is then scanned to track the behaviour of the dye and radioactive particles.

The pathologist also looks for any node with an ex-vivo count ten times higher than for a non-sentinel mode. Or, he or she may identify any node with a ex-vivo 10 times greater than the background count, or any radioactive ‘hot spot‘ with counts more than 25 to 30 times higher second ex-vivo. (Second ex-vivo means a second sample is extracted, combined with fluid, returned to the body, and compared with the orignal base-line readings)

 

 
 

The pathologist looks for radioactive ‘hot spots’ in the sentinel node

 
It will take at least 40-60 minutes for the re-injected technetium sulphur colloid to migrate to the sentinel lymph nodes. Some protocols even recommend up to 4 hours between injection and subsequent mapping. The blue dye (usually isofulfan) however, is very rapidly taken up by the lymphatic system and must be injected less than 10 minutes before the anticipated surgical extraction.

Tumors are typically ‘hard‘, and are difficult to inject into. If one attempted to inject inside the tumor, most of it would leak out along the needle track, into a peritumoral (‘beside’ the tumor) location anyway. Because of this, injection sites will typically either be ‘intra‘ (within the tumor) or ‘peritumoral‘(beside), subdermal above the tumor (below the skin but above the tumor), or given in the subareolar region (beneath the nipple).

The practice of using these procedures to locate the sentinel lymph node and to trace the movement of lymphatic flow, is called ‘lymphoscintigraphy‘. (“Lymphatic mapping” is a general term for various techniques that trace lymphatic pathways and lymphovascular invasion, while ‘scintigraphy‘ specifically implies an injection of radioactive material.)

Specialized surgeons need to gain experience in the technique

 
Not all surgeons perform the sentinel node biopsy technique, although it is easy. The usual reason is that their hospital has not purchased the extra equipment needed to do it. A dedicated, formal training program is usually required as a prerequisite, as well as about 20 SLN biopsies with ‘backup‘ axillary dissections. With experienced practitioners, the sentinel lymph node identification rate (the sensitivity) should be as high as 90%, with a false-negative rate of about 10%, though the rate of false-negative findings is decreasing.

What does the SLN histological report say?

 
The histopathological report from the sentinel lymph node biopsy will usually state how many lymph nodes were actually removed in the specimen, and how many (if any) of those nodes contained cancer cells. The report will often also state whether there is nodal involvement detected through ‘special‘ techniques such as immunostaining and molecular analysis. At a minimum, the SLN report should identify all ‘macrometastases‘ greater than 2 mm. Macro-metastasis is kind of a funny word; it basically means a ‘normal‘ sized metastasis that can be easily seen and physically measured. The term has arisen as a contrast to the emergent idea of ‘micro-metastasis‘, which refers to tiny, ‘microscopic‘ amounts of malginant cells, or even singular malignant cells (dcis with microinvasion).
 

 
In routine clinical practice, a pathologists will employ a serial sectioning technique, using eosin and hematoxylin staining (H&E) to give an optimal evaluation of the sentinel lymph nodes. Generally speaking, the volume of metastatic disease (evident through the number of stained sentinel nodes and the density of the staining) has proven to be the best predictor of involvement of the non-sentinel axillary lymph nodes. (The size/diameter of the primary breast tumor is thought to be the ‘next best‘ predictor for axillary node metastasis.)

Sensitivity and false negatives of cancer metastisis

 
As mentioned, the average sensitivity of the SLN biopsy is about 90% with a false negative rate of about 10%. A positive lymph nodes result means that malignant cancer cells have metastized beyond the original cancer site to some of the sentinel lymph nodes. “Negative“, means that the sentinel lymph nodes are clear. ‘False negatives‘ are generally the result of
a) not finding a sentinel lymph node or
b) the absence of a sentinel lymph node,
c) metastasis of the primary tumor to some area besides the axillary region, or
d) because the lymphatic channels have already been corrupted by the tumor cells, and/or tumor metastasis to axillary lymph nodes has already occurred.

In older patients, a false negative assessment might also be attributed to an excessive amount of fatty tissue within the lymphatic channels which impairs the absorption of the investigative fluids.

Other considerations for using the SLN staging technique

 
If axillary adenopathy is clinically palpable, (i.e. swollen lymph nodes) then a sentinel lymph node biopsy should absolutely NOT be performed. (axillary adenopathy means simply enlarged lymph nodes). The general consensus of opinion is that once metastases is confirmed axillary lymph node removal should be carried out immediately. The SLN biopsy is redundant and useless by that point.

Note: The SLN staging technique is not generally used if the presenting diagnosis is DCIS, because the risk of lymph node metastasis is thought to be very low. The pros and cons of using sentinel lymph node biopsies for breast cancer staging, of which there are few if any, continue to be a subject of debate.

---

If you wish to go through some common Q&A, visit this page, and scroll near the bottom.

In the meantime, here are just a few more…

• How does a sentinel lymph node biopsy feel? You may feel a sharp sting or burn from the local anesthetic used to numb the biopsy site or from the dye or tracer. Feeling pressure or warmth during the biopsy is common and normal, however you should feel little or no pain what-so-ever. If you have pain, be sure to tell your doctor. If you also feel like you are experiencing an allergic reaction, make sure you tell your doctor immediately. This is a possibility when the dye is being used. Ensure that you inform your doctor if you have had any allergic reactions to local anesthesia in the past.
• When should I call my doctor? A biopsy may be sore for several days, and a small amount of bleeding is normal. Ask your doctor how much drainage to expect, and call your doctor immediately if you have an increase in pain, redness, or swelling at the biopsy site, a fever, an increase in bleeding or drainage such as pus, or any swelling in your arm.
• What affects the sentinel lymph node test? It may not be possible to have a clear result from the small sample taken during a sentinel lymph node biopsy. Surgery to remove more lymph nodes (sentinel lymph node dissection) may be needed.
• What are the results of sentinel lymph node biopsy? Normal – the dye or tracer flows evenly to the sentinel lymph node, the lymph node has normal numbers of lymph node cells, the structure of the lymph node and the cells look normal, and no cancer is present. Abnormal – The dye or tracer does not flow evenly to the sentinel lymph node, the sentinel lymph node cannot be identified, or cancer cells may be seen.
• Where would the cancer cells spread to? Cancer cells may start in the lymph nodes, such as Hodgkin’s and non-hodgkin lymphoma but often breast cancer spreasds to the lymph nodes. Cancer cells may have spread or metastasized from other sites, such as breast cancer cells or melanoma cells.
• What exactly are lymph nodes?Lymph nodes, commonly known as glands or lymph glands, are small, round oval structures made up of connective tissue. Lymph nodes are found throughout the body and are connected by lymphatic vessels that are very similar in both structure and function to blood vessels. The lymph nodes and lymph vessels carry lymphatic fluid (or lymph fluid) around the body. The lymph nodes play an important role in the immune system and contain certain types of immune cells. These include white blood cells that help fight bacterial infection and viral infection, allergies and invading foreign agents. This is why often if we have an infection, strep throat for example, we will have swollen neck lymph nodes, in other words swollen glands that will be palpable. Painful lymph nodes are often caused by a fluid build-up in the gland from infection or other benign causes.
• What happens if you already have lymph node swelling? Although there are many reasons for swollen nodes, including infections – both viral and bacterial, allergies and injuries to the area, it is best to be cautious and biopsy any swollen lymph nodes to determine if there are cancer cells present, this is particularly important if there is a primary malignalnt lesion. Painful lymph nodes that are tender, soft and moveable are often more related to infections. If you have lymph node enlargement and a breast cancer diagnosis your health care provider may recommend a fine-needle aspiration guided by ultrasound or a core needle biopsy. If the nodes do contain cancer cells then complete removal is indicated immediately. Supraclavicular lymph node and those in the neck can also be swollen from a spread of breast cancer.

---

References

1. Evaluation of Sentinel Lymph Nodes in Breast Cancer. Histopathology 2005, 46, 697-706
2. Kelley MC, Hansen N, McMasters KM. Lymphatic Mapping and Sentinel Lymphadenectomy for Breast Cancer. American Journal of Surgery. 188 (2004) 49-61.
3. Aasvold JN., Alazraki NP. Update on Detection of Sentinel Lymph Nodes in Patients With Breast Cancer. Seminars in Nuclear Medicine. 35: 116-128. 2005
4. Vijayakumar V, Boerner PS, Vani AB, Vijayakumar S. A Critical Review of Variables Affecting the Accuracy and False-Negative Rate of Sentinel Node Biopsy Procedures in Early Breast Cancer. Nuclear Medicine Communication 2005; 26: 395-405.
5. Bass SS, Cox CE, Ku NN, Berman C, Reintgen D. The Role of Sentinel Lymph Node Biopsy in Breast Cancer. J. Am. Coll. of Surgery Vol. 189, no 2, August 1999, 183-194.
6. Fuhrman GM. Sentinel Lymph Node Mapping and Biopsy for Ductal Carcinoma In Situ and Other Controversial Indications. The American Surgeon, May 2004; Vol 70, N. 5, 404-407
7. Clinical practice guidelines for the care and treatment of breast cancer: sentinel lymph node biopsy, Cantin J, Scarth H, Levine M, Hugi M, JAMC,July 2001,165(2)
8. Kuerer HM, Newman LA. Lymphatic Mapping and Sentinel Lymph Node Biopsy for Breast Cancer: Developments and Resolving Controversies. J Clin. Oncol. Vol 23, Number 8, march 10, 1698-1705, 2005
9. Kuehn T, Bembenek A, Decker T, Munz DL, Sautter-Bihl ML, Untch M, Wallwiener D. A Concept for the Clinical Implementation of sentinel Lymph Node Biopsy in Patients with Breast Carcinoma with Special Regard to Quality Assurance. Cancer Feb. 1, 2005; Vol 103, N.3, 451-461.
10. Stell, VH., Flippo, TS., Norton, HJ., Whilte Jr., RL., Sentinel Lymph Node Biopsy After Neo-adjuvant Chemotherapy in Breast Cancer. The Breast Journal, (Dec. 2010)
11. East JM, Valentine CS, Kanchev E, Blake GO.Sentinel lymph node biopsy for breast cancer using methylene blue dye manifests a short learning curve among experienced surgeons: a prospective tabular cumulative sum (CUSUM) analysis.BMC Surg. (Jan. 2009) 27;9:2.
12. Kim T, Giuliano AE, Lyman GH: Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer (2006) , 106:4-16.
13. Daniele A, Zito AF, Giannelli G, Divella R, Asselti M, Mazzocca A, Paradiso A, Quaranta M.Expression of metalloproteinases MMP-2 and MMP-9 in sentinel lymph node and serum of patients with metastatic and non-metastatic breast cancer.Anticancer Res. (Sep. 2010 ) 30(9):3521-7.

Back to breast cancer staging list or to the brand new homepage.