Sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph node/s is/are the target organs primarily reached by metastasizing cancer cells from the tumor. Thus, sentinel lymph nodes can be totally void of cancer because they were detected prior to dissemination.
The spread of some forms of cancer usually follows an orderly progression, spreading first to regional lymph nodes, then the next echelon of lymph nodes, and so on, since the flow of lymph is directional, meaning that some cancers spread in a predictable fashion from where the cancer started. In these cases, if the cancer spreads it will spread first to lymph nodes (lymph glands) close to the tumor before it spreads to other parts of the body. The concept of sentinel lymph node surgery is to determine if the cancer has spread to the very first draining lymph node (called the "sentinel lymph node") or not. If the sentinel lymph node does not contain cancer, then there is a high likelihood that the cancer has not spread to any other area of the body.
The concept of the sentinel lymph node is important because of the advent of the sentinel lymph node biopsy technique, also known as a sentinel node procedure. This technique is used in the staging of certain types of cancer to see if they have spread to any lymph nodes, since lymph node metastasis is one of the most important prognostic signs. It can also guide the surgeon to the appropriate therapy.
There are various procedures entailing the sentinel node detection:
- Preoperative planar lymphoscintigraphy
- Preoperative planar lymphoscintigraphy in conjunction with SPECT/CT [single photonemission CT (SPECT) with a low-dose CT]
- Intraoperative visual blue dye detection
- Intraoperative fluorescence detection (fluorescence image-guided surgery)
- Intraoperative gamma probe/Geiger meter-detection
- Postoperative scintigraphy of main specimen with planar acquisition
In everyday clinical activity, entailing sentinel node detection and sentinel lymph node biopsy, it is not requested to include all different techniques listed above. In skilled hands and in a center with sound routines, one, two or three of listed methods can be considered sufficient.
To perform a sentinel lymph node biopsy, the physician performs a lymphoscintigraphy, wherein a low-activity radioactive substance is injected near the tumor. The injected substance, filtered sulfur colloid, is tagged with the radionuclide technetium-99m. The injection protocols differ by doctor but the most common is a 500 μCi dose divided among 5 tuberculin syringes with 1/2 inch, 24 gauge needles. The sulphur colloid is slightly acidic and causes minor stinging. A gentle massage of the injection sites spreads the sulphur colloid, relieving the pain and speeding up the lymph uptake. Scintigraphic imaging is usually started within 5 minutes of injection and the node appears from 5 min to 1 hour. This is usually done several hours before the actual biopsy. About 15 minutes before the biopsy the physician injects a blue dye in the same manner. Then, during the biopsy, the physician visually inspects the lymph nodes for staining and uses a gamma probe or a Geiger counter to assess which lymph nodes have taken up the radionuclide. One or several nodes may take up the dye and radioactive tracer, and these nodes are designated the sentinel lymph nodes. The surgeon then removes these lymph nodes and sends them to a pathologist for rapid examination under a microscope to look for the presence of cancer.
A frozen section procedure is commonly employed (which takes less than 20 minutes), so if neoplasia is detected in the lymph node a further lymph node dissection may be performed. With malignant melanoma, many pathologists eschew frozen sections for more accurate "permanent" specimen preparation due to the increased instances of false-negative with melanocytic staining.
There are various advantages to the sentinel node procedure. First and foremost, it decreases lymph node dissections where unnecessary, thereby reducing the risk of lymphedema, a common complication of this procedure. Increased attention on the node(s) identified to most likely contain metastasis is also more likely to detect micro-metastasis and result in staging and treatment changes. The main uses are in breast cancer and malignant melanoma surgery, although it has been used in other tumor types (colon cancer) with a degree of success. Other cancers which have been investigated with this technique are penile cancer, urinary bladder cancer, prostate cancer, testicular cancer and renal cell cancer.
As a bridge to translational medicine, various aspects of cancer dissemination can be studied using sentinel node detection and ensuing sentinel node biopsy. Tumor biology pertaining to metastatic capacity, mechanisms of dissemination, the EMT-MET-process (epithelial–mesenchymal transition) and cancer immunology are some subjects which can be more distinctly investigated.
However, the technique is not without drawbacks, particularly when used for melanoma patients. This technique only has therapeutic value in patients with positive nodes. Failure to detect cancer cells in the sentinel node can lead to a false negative result — there may still be cancerous cells in the lymph node basin. In addition, there is no compelling evidence that patients who have a full lymph node dissection as a result of a positive sentinel lymph node result have improved survival compared to those who do not have a full dissection until later in their disease, when the lymph nodes can be felt by a physician. Such patients may be having an unnecessary full dissection, with the attendant risk of lymphedema.
The concept of a sentinel node was first described by Gould et al. 1960 in a patient with cancer of the parotid gland and was implemented clinically on a broad scale by Cabanas in penile cancer. The technique of sentinel node radiolocalization was co-founded by James C. Alex, MD, FACS and David N. Krag MD (University of Vermont Medical Center) and they were the first ones to pioneer this technique for the use of cutaneous melanoma, breast cancer, head and neck cancer and Merkel cell carcinoma. Confirmative trials followed soon after. Studies were also conducted at the Moffitt Cancer Center with Charles Cox, MD, Cristina Wofter, MD, Douglas Reintgen, MD and James Norman, MD.
- ALMANAC, Axillary Lymphatic Mapping Against Nodal Axillary Clearance trial
- Robbins and Cotran, Pathological Basis of Disease 8th edition pp. 270
- Sherif A, Garske U, de La Torre M,Thörn M, Hybrid SPECT-CT - An additional technique for sentinel node detection of patients with invasive bladder cancer, Eur Urol. 2006 Jul;50(1):83-91. PMID16632191
- Leijte JA, Valdés Olmos RA, Nieweg OE, Horenblas S. Anatomical mapping of lymphatic drainage in penile carcinoma with SPECT-CT: implications for the extent of inguinal lymph node dissection. Eur Urol. 2008 Oct;54(4):885-90. PMID 18502024
- Tanis PJ, Boom RP, Koops HS, Faneyte IF, Peterse JL, Nieweg OE, Rutgers EJ, Tiebosch AT, Kroon BB (2001a). Frozen section investigation of the sentinel node in malignant melanoma and breast cancer. Ann Surg Oncol 8:222-6. PMID 11314938.
- Sherif A, De La Torre M, Malmstrom PU, Thorn M. Lymphatic mapping and detection of sentinel nodes in patients with bladder cancer. J Urol. 2001 Sep;166(3):812-5. PMID 11490224
- Intraoperative sentinel node detection improves nodal staging in invasive bladder cancer.Liedberg F, Chebil G, Davidsson T, Gudjonsson S, Månsson W.J Urol. 2006 Jan;175(1):84-8; discussion 88-9.
- The sentinel lymph node concept in prostate cancer - first results of gamma probe-guided sentinel lymph node identification.Wawroschek F, Vogt H, Weckermann D, Wagner T, Harzmann R.Eur Urol. 1999 Dec;36(6):595-600.
- Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition.Ganswindt U, Paulsen F, Corvin S, Eichhorn K, Glocker S, Hundt I, Birkner M, AlberM, Anastasiadis A, Stenzl A, Bares R, Budach W, Bamberg M, Belka C.BMC Cancer. 2005 Jul 28;5:91.
- Detection of early lymph node metastases in prostate cancer by laparoscopic radioisotope guided sentinel lymph node dissection.Jeschke S, Nambirajan T, Leeb K, Ziegerhofer J, Sega W, Janetschek G.J Urol. 2005 Jun;173(6):1943-6.
- Lymphatic mapping and gamma probe guided laparoscopic biopsy of sentinel lymph node in patients with clinical stage I testicular tumor.Ohyama C, Chiba Y, Yamazaki T, Endoh M, Hoshi S, Arai Y.J Urol. 2002 Oct;168(4 Pt 1):1390-5.
- SPECT/CT and a portable gamma-camera for image-guided laparoscopic sentinel node biopsy in testicular cancer.Brouwer OR, Valdés Olmos RA, Vermeeren L, Hoefnagel CA, Nieweg OE, Horenblas S.J Nucl Med. 2011 Apr;52(4):551-4.
- Bex A, Vermeeren L, de Windt G, Prevoo W, Horenblas S, Olmos RA. Feasibility of sentinel node detection in renal cell carcinoma: a pilot study. Eur J Nucl Med Mol Imaging. 2010 Jun;37(6):1117-23. PMID 20111964
- Sherif AM, Eriksson E, Thörn M, Vasko J, Riklund K, Ohberg L, Ljungberg BJ. Sentinel node detection in renal cell carcinoma. A feasibility study for detection of tumour-draining lymph nodes. BJU Int. 2011 Aug 24. doi: 10.1111/j.1464-410X.2011.10444.x. PMID 21883833
- Malmstrom PU, Ren ZP, Sherif A, de la Torre M, Wester K, Thorn M.Early metastatic progression of bladder carcinoma: molecular profile of primary tumor and sentinel lymph node.J Urol. 2002 Nov;168(5):2240-4. PMID 12394767
- Marits P, Karlsson M, Sherif A, Garske U, Thörn M, Winqvist O. Detection of immune responses against urinary bladder cancer in sentinel lymph nodes. Eur Urol. 2006 Jan;49(1):59-70. PMID 16321468
- Wagman LD. "Principles of Surgical Oncology" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
- Thomas J (2008). Prognostic false-positivity of the sentinel node in melanoma. Nat Clin Pract Oncol. 5(1):18-23. PMID 18097453.
- Gould EA , Winship T , Philbin PH , Kerr HH. Observations on a "sentinel node" in cancer of the parotid. Cancer 1960 ; 13 : 77 – 8. PMID 13828575
- Cabanas RM . An approach for the treatment of penile carcinoma. Cancer 1977; 39:456 – 66,PMID 837331
- Tanis PJ, Nieweg OE, Valdes Olmos RA, Th Rutgers EJ, Kroon BB (2001b). History of sentinel node and validation of the technique. Breast Cancer Res 3:109-12. PMID 11250756.
1. Alex JC, Krag DN. Gamma-Probe-Guided Localizaton of Lymph Nodes, Surg Onc 1993, 2: 137-44.
2. Alex JC, Weaver DL, Fairbanks JT, Rankin BS, Krag DN. Gamma-Probe-Guided Lymph Node Localization in Malignant Melanoma, Surg Onc 1993; 2: 303-308.
3. Krag DN, Weaver DL, Alex JC, Fairbanks JT. Surgical Resection and Radio-localization of the Sentinel Node in Breast Cancer Using a Gamma Probe. Surg Onc 1993; 2: 335-340.
4. Krag DN, Meijer SJ, Weaver DL, Loggie BW, Harlow SP, Tanabe KK, Laughlin EH, Alex JC. Minimal Access Surgery for Staging Malignant Melanoma. Arch Surg 1995; 130: 654-658.
5. Alex JC and Krag DN. Gamma Probe Guided Resection of Radiolabeled Lymph Nodes. Surg Onc Clin N Am 1996; 5 (1): 33-41.
6. Alex JC, Krag DN, Meijer S, Weaver DL, Loggie. Sentinel Node Radio-Localization in Head and Neck Melanoma. Arch Otolaryngol Head Neck Surg 1998; 124: 135-140.
7. Alex JC. The Application of Sentinel Node Radiolocalization to Solid Tumors of the Head and Neck – a Ten Year Experience. Laryngoscope, 2004; 114: 2-19.