Standardization of sentinel lymph node biopsy in breast carcinoma

Nothing is as dear to a surgeon as the technical conduct of surgery. That is what has defined each of us and why we pay homage to our history by associating our predecessor's names with specific procedures. Advances in surgery are made rarely by leaps and bounds but more commonly by small, incremental steps. The technologic improvement associated with the advance of a specific procedure often is made by several, if not many, individuals at the same time, such that there is parallel but divergent progress. The development and implementation of sentinel lymph node biopsy (SLNB) for the staging of solid organ malignancies illustrates how the goal of a technical procedure (i.e., the mapping of lymphatic drainage from a primary tumor) can be achieved with numerous iterations of a surgical procedure involving variables related to the technical conduct of an operation.

When Morton et al. first described their experience with SLNB in melanoma, they very clearly described the technical details of the procedures and, in fact, the title of their report reflected this.1 Giuliano et al. essentially transferred the same technical component of lymphatic mapping to breast carcinoma and reported their experience, describing how isosulfan blue (lymphazurin) was injected in a peritumoral fashion for lymphatic mapping.2 Since then, there have been numerous other publications that have described various technical differences in lymphatic mapping and SLNB relating to such variables as the agent used for lymphatic mapping (i.e., vital blue dye, radiocolloid, etc.), the location of injection of the lymphatic mapping agent (i.e., peritumoral, subdermal, dermal, subareolar, etc.), and even the definition of a sentinel lymph node. The variations in the technical conduct of SLNB have been investigated and reported; however, they are beyond the scope of the current editorial, because there are now approximately 350 publications per year on SLNB in patients with breast carcinoma.3 Those publications describe potential improvements in the procedure related to the objectives of improving the sensitivity, specificity, and accuracy for lymphatic mapping and lymph node staging of solid organ malignancies.

There are now numerous ways to perform an SLNB; and, among major groups of breast surgeons, controversy remains regarding the optimal technique of SLNB. Thus, no standard has been developed in the U.S. A Consensus Conference of international experts was held on April 19–22, 2001, in which the data from greater than 10,000 SLNB procedures were analyzed.4 Despite the extensive experience of that group, the conclusions reached in terms of the technical aspect of SLNB did not produce a standard for the specifics of the operation. The use of radiocolloid in combination with blue dye was endorsed, but the Consensus Panel did not specifically recommend doses or routes of administration. Furthermore, the 2003 Consensus Statement entitled Guidelines for Performance of Sentinel Lymphadenectomy from the American Society of Breast Surgeons addressed the technique in a single sentence by stating that the sentinel lymph node identification rate is higher when a combination technique is used.5

In this issue of Cancer, Kuehn et al. detail the standardization of procedural components of SLNB as well as the pathologic examination for a nationwide implementation.6 The German Society of Senology appointed a multidisciplinary group of physicians involved in the management of patients with breast carcinoma to review the currently available descriptions of SLNB and to develop a standard for the uniform implementation throughout Germany. This group was interested specifically in assuring that the adopted technique would maintain the highest level of quality assurance, so that goal of lymphatic mapping and accurate lymph node staging was not compromised. This appears to be the appropriate time to develop standards related to the technical conduct of SLNB for two reasons: 1) It has been implemented widely and has been adopted as the standard of practice by many7, 8; and 2) there are numerous reports that have compared the various iterations of the technical procedure, and the impact on accuracy of staging is minimal.9, 10 However, Kuehn et al. fully understand that SLNB involves more than the surgeon, and they offer guidelines to the technical requirements of a hand-held γ probe, the experience of the surgeon, and the appropriate patient/tumor characteristics.

It is important to note that Kuehn et al. offer only guidelines and recommendations and do not appear to mandate a specific technique of SLNB. For example, it is recommended that both isosulfan blue and radiocolloid be used for lymphatic mapping, although there is some variability in the recommended amounts and location of injection of either agent. Furthermore, the site of injection of the radiocolloid may be either subdermal or subareolar, allowing the surgeon some leeway in the actual technical conduct of SLNB. Kuehn et al. clearly recognize that SLNB is more than a surgical technique, in that it involves other disciplines (such as nuclear medicine, radiology, and pathology) to ensure accurate lymph node staging of the patient with breast carcinoma. To this end, their group has developed requirements for the radiocolloid aspect of the procedure and has developed a checklist to document satisfactory resources within nuclear medicine. The impact of nuclear medicine in these recommendations is demonstrated by the observation that the use of static lymphoscintigraphy is recommended strongly, despite data demonstrating that it may not be helpful.11

In their original report, Giuliano et al. simply stated that histopathologic analysis was performed with immunohistochemistry reserved retrospectively for the false-negative sentinel lymph nodes.2 Since that report, the pathologic examination of the sentinel lymph node has expanded such that routine immunohistochemistry and even advanced molecular techniques, such as polymerase chain reaction (PCR), have been reported.12 Cserni et al. surveyed 382 European pathology units and identified significant disparities in the histopathologic examination and reporting of results from SLNB specimens, such that there were no standards.13 Routine molecular examination was used rarely (4%), but routine immunohistochemical examination using a variety of cytokeratin antibodies was common (71%). Even the distances between step sections for hematoxylin and eosin staining was variable, ranging from 10 μM to > 500 μM. The standards put forth by Kuehn et al. are much more specific with regard to histopathologic examination of the sentinel lymph node than the technique itself; serial step sections are performed at 500-μM intervals, and immunohistochemical and molecular techniques are not to be performed in a routine fashion. Cserni et al. also identified variations in the reporting of the results with specific regard to micrometastatic disease, which is standardized in the guidelines by Kuehn et al. that essentially replicate the American Joint Committee on Cancer/International Union Against Cancer system.14

The role of SLNB in treatment decisions is much harder to standardize, because these decisions inherently are individualized based on a variety of factors. However, until further data are available, Kuehn et al. recommend completion axillary dissection of Level I and II lymph node basins in those patients with histopathologically positive sentinel lymph nodes, although patients with isolated tumor cells detected only by immunohistochemical methods need no further local treatment (either surgery or radiotherapy). The additional recommendations for the use of adjuvant therapy (either hormonal or chemotherapy) are left to the discretion of the treating physicians.

Kuehn et al. have done a remarkable job in developing standardized guidelines for the implementation of SLNB on a national scale. Although continuing controversies remain regarding various aspects of SLNB, the standardization of the technique, pathologic examination, and reporting will ensure the uniform treatment of patients with breast carcinoma in Germany. Patient outcomes can be optimized in this fashion as the treatment rendered becomes independent of geography, surgeon, pathologist, or institution. Although the art of surgery allows for some variation in the way in which we conduct a procedure, standardizations are necessary to maintain superior results. It appears that Germany is leading the world in the development of such standards for SLNB in breast carcinoma, and the rest of us should take notice.