Hultborn and colleagues were among the first to employ a physiologic strategy for radiocolloid imaging of lymph nodes draining breasts with malignant disease [5]. Their technique involved preoperative injection of the breast parenchyma with postoperative ex vivo imaging of the radical or extended radical mastectomy specimen. The gamma camera image directed the pathologist's dissection of the operative specimen. They also utilized a gamma probe for localization within indistinctly visualized specimens. Their 1954 report remarkably presaged the present-day thinking driving the development of lymphoscintigraphic sentinel node staging of breast carcinoma. They recognized a typical pattern of visualization of some but not all axillary nodes, and concluded, ''This probably indicates a segmental arrangement of the lymph drainage from the breast to the axilla . . .'' or, in our jargon, a sentinel node.

Krag and colleagues were the first to describe the rationale and use of radiocolloid for sentinel node localization in early-stage breast carcinoma [6]. Their technique was adapted from their prior use of a hand-held gamma probe for sentinel node radiolocalization in patients with melanoma [7,8]. Twenty-two consecutive women with biopsy-proved breast carcinoma underwent radiolocalized sentinel lymphadenectomy prior to full axillary dissection. Treatment of the primary lesion was accomplished by either mastectomy or partial mastectomy with planned postoperative radiation therapy. Three of the 22 women had clinically positive (palpable) axillary nodes.

The technique consisted of the injection of 15 MBq (0.4 mCi) technetium-99m (99mTc) sulfur colloid in a volume of 0.5 mL saline into the normal breast tissue adjacent to the lesion or biopsy cavity. Five 0.1-mL injections were made from 1 to 9 h prior to surgery in a 180° arc facing the axilla. Prior to incision, a gamma detector was passed over the axilla. An underlying sentinel node was presumed present when 30 counts in 10 s were detected at the skin surface. Sentinel nodes were found in 18 of the 22 patients. The sentinel node contained meta-static tumor in all seven patients ultimately found, on pathologic examination, to have metastatic axillary lymphadenopathy. In three patients, it was the only site of metastatic disease. Notably, they were unable to identify any sentinel node in 18% of their patients. The investigators did not include an imaging component in the study, commenting on the unsuccessful historical experience.

The same group has more recently reported an updated experience with 50 patients, maintaining their 100% sensitivity and specificity [9]. They have increased their injectate volume to 3 mL and raised a concern about diffusion of injectate obscuring hand-held gamma probe localization of a sentinel node adjacent to the primary lesion. This would, in particular, be a concern in extreme upper outer quadrant lesions.

What is most probably the first modern experience using a radiocolloid to visualize the physiologic lymphatic drainage of the breast was published by Vendrell-Torne and associates [10]. They mapped drainage from injections in the four quadrants of the breast as well as the subareolar region utilizing colloidal gold-198. No attempt to visualize the first draining focus was made. They clearly established the presence of unexpected, sometimes multiple, pathways of drainage to axillary, internal mammary and supraclavicular sites in a significant minority of normal subjects.

Uren and colleagues were the first to report the use of radiocolloid injection of the primary lesion site to image the pathways of lymphatic drainage in patients with breast cancer [11]. They used 99mTc-labeled antimony trisulfide (99mTc-

Sb2S3) with a 3-12-nm particle size. Injections of 0.1-0.2 mL were placed at the four clock quadrants using a tuberculin syringe and a 25-gauge needle. The depth of injection (and precise position of the tumor) was determined in each case by high-resolution ultrasound. Activity varied from 2.5 to 7.0 MBq (0.070.19 mCi) for each injection. All studies were performed prior to excision of the tumor. The tumor and adjacent injection sites were subsequently excised within

Lymph Nodes Dye Injection Breast

Figure 1 (a) Anterior view of right chest of a patient with a lower outer-quadrant lesion draining across midline of the breast to the internal mammary nodes. (b) Right lateral view depicting drainage to the ipsilateral axilla. The arrowheads mark the first-tier lymph nodes.

Figure 1 (a) Anterior view of right chest of a patient with a lower outer-quadrant lesion draining across midline of the breast to the internal mammary nodes. (b) Right lateral view depicting drainage to the ipsilateral axilla. The arrowheads mark the first-tier lymph nodes.

1 week. Imaging was performed immediately after injection and at 2.5 h in all patients. In patients with no nodal visualization, a repeat scan was obtained at 4 h. Images were obtained in an anterior view of the chest and axilla in all patients. A lateral or oblique view was added to assess the depth of axillary sentinel nodes. All scans were obtained with a large-field-of-view digital camera with a low-energy, high-resolution collimator. Immediate scanning was performed to identify lymph channels draining the tumor. Delayed scanning was performed to locate persistent uptake in nodes. The sentinel node was considered to be the first node to take up the colloid on the immediate scan or the node with the most activity on the delayed scan.

The ipsilateral axilla was a drainage site in 29 of the 34 patients (85%) and the only drainage site in 18 of them (53%). However, the unpredictability of drainage patterns previously described by Vendrell-Torne was confirmed. Approximately one-third of lateralized tumors demonstrated drainage to the ipsilat-eral axilla and/or internal mammary chain (Figs. 1a and 1b), whereas 20% of upper-quadrant lesions drained to supraclavicular or infraclavicular nodes (Fig. 2). Immediate scans were able to identify lymph channels in only 7 of the 34 patients (21%). This was a potential drawback only in patients with internal mammary node drainage because multiple nodal uptake candidates for sentinel node designation were characteristically present, on delayed scans, in the internal mammary but not the axillary or periclavicular basins. In three patients, no migra-

Internal Mammary Lymph Node
Figure 2 Anterior chest view showing left breast lesion draining directly into an infraclavicular lymph node as well as to an internal mammary lymph node. Arrowheads mark lymph nodes. Sternum and clavicles are delineated with a radioactive marker.

tion of tracer from the injection site was seen. In one of these, gross chest wall and axillary tumor masses were present.

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