Periareolar Injection and the Sentinel Node in Breast Cancer
Abstract & Commentary
Synopsis: A comparison between the standard peritumoral injection site and the periareolar site showed a possible advantage for the latter in identifying the sentinel lymph node in breast cancer. The technique may also be easier to perform.
Source: Shimazu K, et al. Surgery. 2002;131:277-286.The development of the sentinel lymph node (sln) technique has been a major advance in the area of cancer care. For breast cancer patients, the most widely accepted technique uses a peritumoral injection. Recently, a newer approach using a periareolar injection has been developed which offers potential advantages. This study from Japan reports on 2 separate protocols which will be referred to as study 1 and study 2.
Study 1 included 62 patients with T1-2 breast cancer whose SLN was identified by the peritumoral injection of blue dye into the parenchyma surrounding the tumor or into the wall of the biopsy cavity. After the SLN was identified, a complete axillary lymph node dissection (ALND) was performed in all patients. A SLN was "positive" if metastatic disease was demonstrated by either standard histology or immunohistochemistry after sectioning into 2 mm slices. Nonsentinel nodes were examined by a single representative section using routine histology only. A sentinel node was identified in 50 patients (81%), 17 (34%) of whom harbored metastatic disease. The SLN was the only positive node in 5 patients (29%). The false-negative rate was 5.5%.
Study 2 included 93 patients with T1-2 breast cancer whose SLN was identified using both blue dye and a radiotracer injection. In all 93 patients, the blue dye was injected using a peritumoral injection. The radiotracer injection, given the day before surgery, was peritumoral in 41 patients and periareolar in 52 patients. The periareolar injection was administered into 4 equally spaced periareolar locations, both intradermally and subdermally, with a total of 2 mL of 30-80 MBq of Tc-tin colloid. A complete ALND was performed only if: 1) the SLN could not be identified, 2) the tumor size was greater than 3 cm, or 3) the SLN was positive by frozen section.
Compared with the standard peritumoral injection technique, the periareolar injection had a statistically significant advantage both for preoperative SLN identification by lymphoscintigraphy (90% vs 51%) as well as intraoperative SLN identification using the gamma probe (98% vs 85%).
Comment by Kenneth W. Kotz, MD
Shimazu and colleagues present data from 2 studies: performance of a standard SLN biopsy using only blue dye with a backup ALND in all patients ("study 1"), and a comparison between peritumoral and periareolar injection of radiotracer (study 2). Although not explicitly stated, it appeared that the 2 studies were performed concurrently rather than sequentially since patients with larger tumors "were preferentially enrolled" in study 1 where a backup ALND would always be performed. It should be emphasized that it is not stated whether the patients in study 2 were randomly assigned or not to 1 of the 2 arms.
In study 2, the periareolar injection site appeared superior to the standard peritumoral injection site. This might be expected due to the unique anatomy of the breast lymphatics. First, uptake of radiotracer in the areola is facilitated by the rich lymphatic network when compared with the breast parenchyma. Second, the direction of lymph flow is toward the subareolar lymphatic plexus and then toward the axillary nodes. This may account for the successful identification of SLNs in multifocal breast cancer.1 Third, the injection can be either intradermal or subdermal due to the abundant number of connecting lymphatic vessels in the areola. Fourth, the sentinel node is not obscured by radioactivity from tumors in the upper, outer quadrant (shine-through phenomenon).
The learning curve for accurately identifying the SLN after a peritumoral injection is well known. Part of the challenge is correctly identifying the appropriate peritumoral site for injection, particularly for nonpalpable tumors. An advantage of the periareolar injection is its technical simplicity. Unlike study 1, where a learning curve was demonstrated, the rate of SLN localization did not improve during the performance of study 2.
Tc-tin colloid, available in Japan, has a larger particle size than Tc-sulfur colloid, available in the United States. Because the radioactivity is retained longer in the lymph node, detection with an intraoperative gamma probe can be performed the day after injection and, in addition, one minimizes the labeling of non-SLNs. A radiotracer with a larger particle size also passes into the lymphatic vessels with more difficulty. This may account for the low lymphoscintigraphic detection rates that have been reported with the use of large particle colloid when using the peritumoral injection site (51% in this study). This low SLN detection rate seems to be avoided with use of a periareolar injection (90% detection rate in this study) possibly due to the rich periareolar lymphatics which are more easily penetrated by the larger colloid preparation. Of note, a previous biopsy, particularly between the axilla and areola, reduced the ability to identify the sentinel node by lymphoscintigraphy after periareolar injection of a radiocolloid. Importantly, however, the SLN could still be identified intraoperatively with the gamma probe.
In study 2, 4 patients had extra-axillary localization of radiotracer, one of whom had an internal mammary node that contained metastatic disease. Because all 4 of these patients had positive axillary nodes, Shimazu et al hypothesize that the flow of lymph may be diverted in the presence of lymphatic vessel obstruction. In cases of clinically positive axillary nodes, they have observed (data not published) a higher rate of extra-axillary radiotracer accumulation when using the periareolar technique.
All in all, the study by Shimazu et al adds to the growing body of literature regarding periareolar injection for the identification of the sentinel lymph node.2-4 Regardless of technique, the optimal SLN identification rate should be > 90%, and the false-negative rate should be < 5%. Each surgeon should know their own false-negative rate, and should validate results before changing technique. However, it remains to be determined how best to perform a SLN biopsy in breast cancer patients.
Dr. Kotz of Hanover Medical Specialists, Wilmington, N.C.
References
1. Schrenk P, et al. Lancet. 2001;357:122.
2. Martin R, et al. Surgery. 2001;130:432-438.
3. Leong S, et al. Breast Cancer. 2000;7:105-713.
4. Bianchi P, et al. Tumori. 2000;86:307-3078.
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