Sentinel Lymph Node Biopsy (SNLB)

The current recommendation of the American Joint Committee on Cancer for melanoma patients with a TIb-T4, NO, MO classification (Balch, 2004) is to have a SLNB. This includes Stages I and II: tumors less than or equal to 1mm up to 4mm, Clark's level IV or greater in Stage I, no regional nodal metastasis found in the clinical staging, and no metastasis to other body parts found in the clinical staging. Melanoma in situ (Tis) and (T1a) generally do not benefit from SLNB as the melanoma has not spread vertically in these stages.

The sentinel lymph node is the first lymph node to which the melanoma tumor drains. This is the first major stop along a lymphatic channel out to the rest of the body. Melanoma spreads through the lymphatic channels, circulatory highways (veins and arteries), or by direct extension of the tumor (growing larger and invading adjacent tissue). It is important to identify this node(s) as tumors don't always drain to the nearest or most anatomically logical node. Additionally, they may drain to more than one lymphatic basin.

More accurate staging and a lower rate of postoperative complications are the main reasons for having a sentinel lymph node biopsy. Nodal status (positive for melanoma spread or negative for no melanoma spread) is the most significant predictor of disease-free survival. Prompt staging leads to earlier treatment.

Studies have shown that only 20% of melanoma patients with a Breslow thickness between 1.5 - 4 mm have metastasis in their sentinel node. This is the 20% that will require removal of all lymph nodes in the drainage basin surrounding a primary melanoma. The procedure carries a higher complication rate (swelling in arms and legs, wound necrosis, infection) and is unnecessary in the majority of melanoma patients.

Finally, errors during pathology testing (approximately 12% of lymph nodes in the conventional routine) can be decreased if a single (sentinel) node is tested in a detailed manner rather than testing the standard few nodal sections in a higher number of lymph nodes per patient.

Sentinel lymph node biopsy is the removal and biopsy of the sentinel lymph node or nodes that drain a primary melanoma. In melanoma, it involves a sequence of events and an experienced medical team including surgery, nuclear medicine and pathology working together. It can be done as an outpatient or inpatient procedure depending on the surgeon, institutional policies, and extent of disease spread. SNLB is done first to stage the extent of melanoma spread, second to remove affected lymph tissues, and third to prevent the complications that occur with more extensive lymph node system removal. Current recommendations are that the SLNB is completed, the patient sent home, and then follow-up removal of additional lymph nodes is done later (if needed) based on the pathology reports.

1. Preoperative Dynamic Lymphoscintigraphy

   First, a low-level radioactive fluid called a tracer (99Tc-sulfur colloid) is injected into the skin surrounding the primary melanoma. This is usually done in the Nuclear Medicine Department of the hospital. Pictures are then taken of the lymphatic drainage system. The radioactive tracer follows the lymphatic channel that melanoma cells would most likely travel and accumulates in the most likely lymph node to have melanoma cells. The location of the lymph node(s) with the highest radioactivity is then marked on the skin with a temporary tattoo for localization during surgery. This is called lymphoscintigraphy and its purposes are to identify the nodes that drain the melanoma, the number of nodes at risk for spreading, and guide their removal by showing their location. It is important especially in melanomas of the head, neck, shoulders or trunk since the anatomical drainage basins in these areas are often different from patient to patient and may drain to multiple basins.
   
   

2. Vital Dye Guidance

   The tracer is then allowed to travel from the tumor to the rest of the system (between 45 minutes to 8 hours depending on your surgeon and the institution's policy). Next, you are taken to the operating room where a blue dye [Lymphazurin (isosulfan) blue] is injected into the skin surrounding the melanoma. This dye helps to visually label the affected lymph nodes. It will leave a temporary discoloration in your skin for a while and turn your urine green for about a day.
   
   

3. Intraoperative Gamma Probe

   Once the tracer has circulated through the body, the surgeon uses a hand held Geiger device that counts the number of gamma rays emitted to locate the sentinel node(s). A loud tone sounds when the radiation level exceeds the background level thus locating the affected node. This "hot spot" is usually the sentinel node. The use of both the Geiger probe and skin tattoos from the lymphoscintigraphy pictures allow the surgeon to make an incision (approximately one-half inch) in the appropriate area. Once open, the blue dyed node(s) and lymphatic pathways should be visible and easily removed.

   
   
   Some sentinel nodes don't take up the blue dye. Some sentinel nodes don't register the highest radioactive reading (the hottest spot). The multi-institutional Sunbelt Melanoma Trial found that if only the hottest lymph node had been removed then 13.1% of the nodal basins with positive SLN's would have been missed. This is why a combination of the radioactive tracer, the lymphoscintigraphy pictures with skin tattoos, and the blue dye are used. It ensures a higher level of locating the true sentinel node.

   
   
   This is also why it is recommended that all blue nodes and all nodes that measure greater than or equal to 10% of the ex vivo radioactive count of the hottest SLN be removed.
   
   

4. Pathology

   The removed lymph nodes are then sent to the pathology lab. This is where controversy exists. There are several ways to examine the node and decide if melanoma cells are present. One is called a frozen-section where the node is sectioned, stained and frozen. The results are obtained within 30-60 minutes. The other is a more permanent section where the node is sliced into smaller sections and stained with immunohistochemicals with the results being ready in 5-7 days.

   General consensus is that the more permanent sectioning has a higher rate of accuracy (97-98%) whereas the frozen sectioning creates tissue artifact leading to an 11% false negative rate. This means that 11% of patients think they don't have a spread of their melanoma when they do. Additionally, cutting up part of the node for frozen-section analysis and then sending the rest for immunohistochemical analysis means that a lot of tissue is not examined on a more detailed basis and micrometastasis may be missed.

   A third procedure called imprint cytology can be used instead of frozen sectioning. In this, the node is transected and each cut surface is placed on a glass slide and fixed or air-dried and then stained. The advantages of this procedure are that it is easier to perform, doesn't result in wasted tissue from freezing artifact, and is less expensive. The disadvantage is the same as for frozen sectioning, it is not as sensitive a test. For these reasons, frozen-sectioning has fallen out of use in favor of the longer immunohistochemical testing. This is also why a SLNB is performed on one day, the patient is sent home to await the pathology report, and then readmitted if the node has melanoma cells. It has been suggested that frozen-sectioning may be useful in head and neck melanomas, especially with an intraparotid SLN since it may avoid a second surgery and thus decrease the possibility of facial nerve injury.

Generally, a patient who has undergone a wide local excision (WLE) when the melanoma was removed do not benefit as much from having a SLNB because the wide excision distorts the lymphatic drainage basin by cutting it up. However, some surgeons will do a SLNB even after a WLE as long as the wound has not been closed with a rotational flap of skin.