Since the sentinel lymph node biopsy (SLNB) technique was first introduced for evaluating the axilla of breast cancer patients, the morbidity associated with axillary dissection has been greatly reduced. However, the rate of lymphedema has ranged from 0% to 13% despite the use of the SLNB,(1-3) and the rates are higher in patients who undergo conventional axillary lymph node dissection (ALND). If there are two independent lymphatic systems, one from the breast (the breast lymphatics) and the other from the arm (the arm lymphatics), and if the metastasis involving the axilla occurs only in the lymph nodes from the breast lymphatics, then mapping and preserving the arm lymphatics might decrease the likelihood of disrupting the lymphatic drainage of the arm and this could result in decreasing the risk of lymphedema both for ALND and SLNB. Thus, we performed this pilot study to determine if there are two independent lymphatic drainage systems, one from the breast and one from the arm, with no metastasis at the arm sentinel lymph node (SLN; the first drained lymph node by definition). The final goal is to prevent lymphedema by performing arm SLN detection, by preserving the arm lymphatic drainage during ALND or SLNB.

The status of the axillary lymph nodes is an important prognostic factor for the treatment of breast cancer. ALND has been widely adopted to identify the exact lymph node status; in addition, SLNB has become a standard treatment method for early stage breast cancers. Lymphedema remains one of the most serious complications of ALND and this occurs in 13% to 52% of the patients with the variations occurring due to the definition and methods of determining lymphedema, the length of follow-up, the number of positive lymph nodes, the use of postoperative irradiation, the body habitus and the BMI.(4-7) Although SLNB has been shown to have a lower morbidity rate than that of ALND, the rate of postoperative lymphedema with SLNB alone has ranged from 0% to 13% with an average of approximately 7%.(1-3)

Although many factors influence the development of lymphedema, the best way and the first step to prevent lymphedema is to preserve the arm lymphatic drainage. Some investigators have suggested that arm lymphatic mapping is helpful to identify and preserve the arm lymphatics. Thompson et al. refers to this new procedure as axillary reverse mapping (ARM) because identification of the arm lymphatics is for preservation, not removal.(8) This is the reverse concept of SLNB where we seek to identify the SLN for removal. Other investigators refer to the arm lymphatics as lymphatic arm drainage (LAD) and they recommend considering the physiology, removing only those nodes draining the breast and leaving in place the lymph nodes involved in the LAD.(9) Prior investigators have shown that this technique is feasible, and they have reported the detection rate for the arm lymphatics or lymph nodes to be 61-71%. In our study, the detection rate for the arm SLN was 71.4%.

To find the role of arm SLN detection in the cases of doing breast SLNB, we also tried the arm SLN detection in the patients which underwent the breast SLNB simultaneously. In our institute, we are performing the biopsy of a suspicious palpable LN as an integral part of SLNB to lower the false negative rate of SLNB.(10,11) Although Given that the excision of palpable LNs may reduce the false negative rate of SLNB, lymphedema rate would be increased. However, if we could define some palpable nodes as an arm SLNs, it would be helpful to reduce the occurrence of lymphedema by preserving a palpable arm SLN which could be misinterpreted as a breast SLN even though it is palpable. Interestingly, most of the arm SLNs were palpable in this study.

The anatomy of the relationship between the arm and breast lymphatics has not yet been defined. It is assumed that there is a different lymphatic drainage system for the arm and breast lymphatic drainage to the axilla. Evaluation of the lymphatic systems is difficult because of the scarcity of detection methods, the small lymphatic channels and the difficult accessibility. Hama et al.(11) showed in a mouse model two different drainage systems by performing two-color spectral fluorescence lymphangiography. Previous studies about the arm SLN also reported that there were variations in the location of lymphatics from arm.(8,9) They both showed the absence of concordance of the arm and breast lymphatic drainage. However, other researchers that performed cadaver studies have reported that the main sentry node in the axilla had the same drainage from the upper limb and the anterior upper torso.(12,13) In addition, in a study of the arm sentinel by Boneti et al.,(14) common pathway of the blue arm lymphatics with the breast lymphatics together with a hot SLN was observed in five (3.9%) patients, although these lymph nodes in the five patients did not contain metastases. In our study, there were two cases of common pathway of the arm and breast SLN, and the arm SLN in one case showed a breast cancer metastasis. Therefore, detection of the arm SLN should be tested in future studies with a larger number of patients and long-term follow up because of the risk of missing a positive axillary node when preserving the arm SLN.

A previous report on detecting the arm SLN showed that lymphazurin (isosulfan blue dye)(8) and patent blue dye (9) could be used for detecting the arm SLN. For the cases that underwent simultaneous breast SLNB and arm SLNB in a previous report, isotope was additionally used for the detection of the breast SLN. We attempted several methods for detecting the arm SLN with using isotope and other dyes (indigocarmine, ICG) because of the risk of severe skin reactions, including necrosis and dermolysis, for the cases with injecting methylene blue dye into the subcutaneous tissue or dermis and due to the difficulty with obtaining lymphazurin (Table 2). This is the first report of a triple detection method being used for increasing the detection rate of the sentinel lymph node. This method was used in three cases. Blue dye for the arm lymphatic drainage and green dye and isotope for the breast SLNB were used in two cases. This method can be applied with other combinations of using an isotope for the arm SLN and blue and green dyes for the breast SLN. Although differentiation of these colors was very difficult, it was possible to differentiate the blue and green dye-stained lymph nodes. Some reports have suggested that using fluorescence imaging for sentinel node biopsy may be effective.(15,16) Kitai et al. reported a high detection rate (94%) with using indocyanine green fluorescence imaging. This approach may help in the differentiation between a green dye stained SLN (the breast SLN) and a blue dye stained SLN (the arm SLN).(16)

The site of dye injection in the arm was the upper inner area. A previous study also chose this area for the injection site of blue dye. This site was chosen simply because it had the most rapid drainage (average flow 2.0 cm/min),(17) and the site also easily hid the tattoo. There was no severe systemic allergic reaction to the employed dyes. After 5 months of follow-up, the blue stain was resolving. In one report that used patent blue dye, the blue stain either disappeared or it was resolving after 2 yr.(9) In a report with using lymphazurin, the skin coloration lasted from 1 week to 6 months.(8) A small dose, another site of the arm or another method such as an isotope should be considered as alternative methods that can be used to avoid prolonged tattooing. We used an isotope method for detecting the arm SLN in 2 cases.

Our study is limited by the small number of patients and the relative inexperience with the procedure we used. Identification and preservation of the arm lymphatic drainage is a novel procedure. Identification and preservation of the arm lymphatic drainage is more difficult than simple biopsy and detection of a SLN, and it likely requires a longer learning curve than that for breast SLNB. The previously reported results for the identification rate and the dissection of lymphatic drainage (71% vs 47%) suggest this discrepancy.(9)

In our preliminary study, metastasis to the arm SLN and a case with common lymphatic drainage posed difficulty for the concept of two separate lymphatic drainage systems. Therefore, the usefulness and safety of arm sentinel lymph node biopsy remains unclear. Nos et al. recently reported on three patients who had breast metastasis in their arms' sentinel nodes.(18) We also found the presence of metastasis in an arm SLN. In addition, we introduced the first triple detection method.

Identifying the arm sentinel lymphatic drainage is possible. Because there were cases of common pathway of the arm and breast lymphatics and metastasis of the arm SLN, we cannot conclude that the arm SLN detection was safe and effective. A subsequent study is needed for the identification of the presence of two different drainage systems of the breast and arm lymphatics and for confirming the absence of metastasis at the arm SLN.