br Various markers have been proposed to mark
Various markers have been proposed to mark positive lymph nodes before NAC with various ways to localize them before surgery: metallic clips, I125 radioactive seeds, tattooing with carbon suspension, sono-graphically visible bioresorbable polymers (Hydromark, Des Plaines, IL), hook wires, endomagnetic markers, radio frequency markers.13-17
We report our initial results on TAD with ALN tattooing after NAC. The primary objective of this study was to determine the intraoperative identification rate (IR) of tattooed nodes and the concordance between sentinel nodes and marked nodes. The sec-ondary objective was to investigate important key points, advan-tages, disadvantages, and possible pitfalls of the procedure.
Patients and Methods
Table 1 Patient Characteristics
Total Patients, n
Lymph Node Biopsy
FNAC nondiagnostic 3 (4.0)
Type of Breast Surgery
Abbreviations: BCT ¼ breast-conserving treatment; CNB ¼ core needle biopsy; ER ¼ estrogen receptor; FNAC ¼ fine-needle aspiration cytology; IDC ¼ invasive ductal carcinoma; IHC ¼ immunohistochemistry.
appropriate candidates for NAC. Breast cancer diagnosis was confirmed using core needle biopsy in all cases. Positive lymph nodes were marked in all patients before treatment. After NAC completion, the axilla was re-evaluated using ultrasound. Six pa-tients had residual axillary disease confirmed using needle biopsy and were excluded from this analysis. Seventy-five patients (74 female and 1 male) in the process of definitive surgery, underwent TAD for axillary surgical staging.
Patients’ data were extracted from medical records, surgical reports, imaging reports, pathology reports, and were analyzed retrospectively.
Clinical and pathological characteristics of all 75 patients are listed in Table 1.
Lymph Node Tattooing and TAD for Axillary Staging After NAC
Figure 1 Intraoperative Identification of Tattooed/Sentinel Lymph Node. Black Pigment and Blue Dye Overlap in Large Areas But, Blue Dyed Efferent Lymphatic Vessels Demonstrate the Presence of a Sentinel Node
In every patient, the axilla was evaluated clinically and using ultrasound. Breast magnetic resonance imaging was performed in most cases. All patients were characterized as cNþ according to clinical and/or ultrasound criteria. Clinical criteria for the consid-eration of ALNs were firm lymph nodes, which were fixed or matted using palpation. The sonographic lymph node criteria consisted of a completely hypoechoic node with no hilum, focal or diffuse hypoechoic lobulation of the cortex, rounded appearance, or diffuse
cortical thickening with a ratio of Bafilomycin A1 thickness/hilum thickness >1.18,19 The most concerning nodes were biopsied in every patient. In patients with more than 2 lymph nodes suspected to be cancerous, biopsy was performed only for the 1 or 2 most abnormal nodes. Four patients underwent ultrasound-guided core needle bi-opsy and 71 patients underwent ultrasound-guided fine needle aspiration biopsy. Histology confirmed axillary invasion in 64 of 75 patients. In 11 patients, node positivity was not established using biopsy, but all of those patients were considered cNþ because of a strong suspicion of axillary invasion.
lymph node size. The greater amount was used for larger nodes. A small amount of ink was injected into adjacent adipose tissue for better visualization during surgery. The number of marked lymph nodes was routinely recorded, with all ALN tattooing procedures performed by 2 breast surgeons.
All patients received anthracycline and/or taxane-based chemo-therapy regimens. Patients with HER2-positive (HER2þ) tumors received anti-HER2 targeted treatment (1 patient with trastuzumab and 26 patients with trastuzumab and pertuzumab).
Surgical Procedure (TAD)
All patients had definitive surgery 3 to 5 weeks after NAC completion. They were routinely subjected to breast lympho-scintigraphy 2 to 12 hours before surgery with the use of a radio-tracer (Tc 99m - albumin nanocoll; Nanocoll GE Healthcare, Little Chalfont, United Kingdom), with 900 to 1200 mCi injected in the subareolar area. During surgery, just after general anesthesia was administered and 10 minutes before the procedure started, 2 mL of methylene blue sterile solution 1% was injected in the subareolar region. A 4- to 7-cm incision was made into the skin for axillary entrance. The axillary cavity was explored carefully to identify and remove SLNs along with all marked lymph nodes. A gamma probe system (Crystal Probe-Automatic; Crystal Photonics GmbH, Berlin, Germany) was used to identify radioactive nodes (hot nodes). Blue-dyed and black-dyed nodes were identified using visual inspection (Figure 1). Lymph nodes with radioactive counts >10% of the ex vivo counts of the hottest SLN and/or blue dye uptake were considered as sentinel nodes. Palpable hard nodes were also removed. The harvested lymph nodes were sent to the pathology lab in different containers, labeled as “sentinels/black pigment,” “sen-tinels/no black pigment,” and “nonsentinels/black pigment” (Figure 2). Intraoperative frozen sections were performed on all lymph nodes for the detection of residual disease and the docu-mentation of black pigment presence. Sentinel and non-SLNs were examined using hematoxylin and eosin staining. Immunohisto-chemistry was not routinely used to detect lymph node metastasis. In case of axillary residual disease, complete ALND was performed. If axillary residual disease was missed in intraoperative specimen frozen sections, but was recognized in permanent sections, ALND was completed during a second intervention. All TAD procedures were performed by 2 breast surgeons.