Sentinel Lymph Node Biopsy for Breast Cancer and Melanoma
Joseph J Bennett, MD Department of Surgery, University of Chicago Hospitals
Breast cancer remains the most common malignancy diagnosed among women today. In 2005, breast cancer was projected to account for 213,000 new cancer diagnoses in women and 41,000 deaths.1 Melanoma will account for 66,000 new cancer diagnoses and almost 8,000 deaths.1 Unfortunately, these staggering numbers are on the rise.
Breast cancer and melanoma are similar in that both are surgically treated for cure by wide resection of skin and soft tissue. The most striking similarity between these two cancers, however, is their propensity to metastasize to regional lymph nodes. It is extremely rare for these cancers to spread systemically without first passing through the first draining lymph node basin. For this reason, the presence or absence of regional lymph nodes is the most significant prognostic variable that predicts survival for patients with either breast cancer or melanoma. Thus, the status of regional lymph nodes dictates staging, prognosis, treatment, and enrollment into clinical trials.2,3
Just over a decade ago, regional nodal basins were assessed by complete lymph node dissections, either in the axilla, the groin, or in the neck, depending on the location of the primary tumor.4 The problem with this approach was that many patients did not ultimately have lymph node metastases, and did not, therefore, benefit from more accurate staging or better locoregional control, although all patients suffered the morbidity of extensive surgery.5–6 In 1992, a new technique involving intra-operative lymphatic mapping was reported for the first time.7 This technique revolutionized the assessment of regional lymph nodes and is now known as sentinel lymph node (SLN) mapping, performed in combination with a sentinel lymph node biopsy (SLNB).7
SLNB Principles and Techniques
Morton and colleagues were the first to demonstrate that lymphatic drainage from a melanoma can be ‘mapped’ by injecting the skin around the tumor with blue dye.7 Injected blue dye was shown to travel through lymphatic channels to the first, or ‘sentinel’, lymph node that drains the tumor (see Figure 1). After intense histologic analysis of the SLN, these investigators were able to show that the pathologic status of the SLN accurately reflected the pathologic status of the entire regional nodal basin. A positive SLN is associated with a higher chance of the remaining nodes containing metastases, while patients with negative SLNs infrequently have other nodes that contain tumor cells.7,8 SLN mapping therefore spares approximately 80–85% of patients with melanoma and 65–70% of patients with breast cancer from having a complete lymph node dissection for what will ultimately be a negative nodal basin.7–10
The technique of SLN mapping has been significantly refined over the past decade. The accuracy of detecting the SLN when using blue dye alone is approximately 80%.7–10 In order to further increase the accuracy of detecting the SLN, a radiolabeled tracer such as technetium-99m-labeled sulfur colloid is also injected at the site of the primary tumor.11 A lymphoscintogram is an X-ray obtained before surgery that localizes the radiolabeled SLN and visually directs the surgeon to the proper node(s) and basin for biopsy. The SLN is now considered ‘hot’ with radioactivity and can be measured quantitatively by a gamma counter probe.The incision is targeted directly over the SLN by using the gamma probe to detect the area of highest radioactivity. The surgeon then follows the blue-colored lymphatic channels to the SLN, in addition to using the gamma counter to find the SLN with the most radioactivity (see Figure 2). After excision, the blue and hot node is counted with the gamma probe ex vivo and the number is recorded. In addition to removing any blue nodes, any remaining nodes in the regional basin that are greater than 10% of the ‘hottest’ node are also removed. Using these combined modalities, the accuracy of detecting the SLN has increased to between 92% and 98%.7–12
Pathologic Assessment of the Sentinel Node
Another significant stride in SLN mapping involves targeted histologic analysis by the pathologist. The pathologist receives a single lymph node, or just a few nodes, which can be subjected to a much more intense and targeted analysis. In addition to performing many levels of tissue slicing with hematoxylin and eosin (H&E)-staining, immunohistochemistry (IHC) is performed as a complement to H&E. IHC involves the use of tumor-specific antibodies to detect micrometastases. IHC confirms the presence of tumor cells in cases where H&E is not definitive, and has also been shown to detect an additional 8–12% of tumor cells that were missed by H&E staining.13–14 The clinical significance of micrometastases detected by IHC only is not completely clear at the present time.
