Sentinel Lymph Node Biopsy Using Methylene Blue Dye and Intraoperative Palpation Method in Node-negative Early Breast Cancer

Nilesh Patil, Prafulla Kumar Das, Kalyan Panday, Kunal Goutam, Bharat Bhusan Satpathy

Acharya Harihar Post Graduate Institute of Cancer, Manglabag, Cuttack-753007, Odisha, India

Correspondence to: Dr. Bharat Bhusan Satpathy; email:

Received: 30 Sept 2020; Revised: 06 Jun 2021; Accepted: 13 Jun 2021; Available online: 31 July 2021


Background: Early breast cancer with clinical or radiological node-negative axilla is treated with breast conservation surgery where lumpectomy with axillary dissection is done. Sentinel lymph node biopsy (SLNB) is an acceptable alternative to axillary clearance and has relatively lesser morbidity. SLNB methods include radioisotope (RI)-guided, blue dye-guided, or a combination of both. However, access to RI can be limited in certain geographic locations. Results: The sensitivity, specificity, false-negative rate (FNR), and accuracy of MB-guided SLNB in our study were 92.8%, 100%, 7.14%, and 97.7%, respectively. Conclusion: The use of MB dye along with intraoperative palpation after meticulous lymph node dissection in each level is more effective and has lower FNR than RI.

Keywords: SLNB, Methylene blue dye, Sensitivity, Specificity, Breast carcinoma

Ann Afr Surg. 2021; 18(4):208–214


Conflicts of Interest: None

Funding: None

© 2021 Author. This work is licensed under the Creative Commons Attribution 4.0 International License.


In breast cancer surgery, investigation of the status of axillary lymph node (ALN) is a pivotal prognostic factor that determines the next course of treatment for the patients. Axillary lymph node dissection (ALND) has been considered as a gold standard for postoperative pathological staging in invasive breast carcinoma. However, this process involves substantial morbidity such as paresthesia and arm numbness, lymphedema, and limited shoulder movement, which adversely affects the patient’s quality of life (1, 2). Hence, there is a paradigm shift in the surgical management of ALNs that evolved from complete axillary lymphadenectomy to a more conservative approach of axillary dissection. Eventually, the introduction of the sentinel lymph node biopsy (SLNB) in carcinoma breast surgery has revolutionized the pathological assessment of ALNs in early breast cancer patients. This method has minimized the occurrence of debilitating adverse events in post-operative patients caused by complete ALND (3). Hence, SLNB has been practiced widely as the standard procedure for axillary staging in early breast cancer patients (4–6).

There are various tracer techniques employed to perform SLNB, and each has its own limitations and advantages. Some surgeons prefer to use radioisotopes (RI) or vital dyes alone, whereas others prefer dual tracer-guided SLNB. However, the major limitations of radioactive tracer techniques are their high cost, technical complexity, and logistics (7). Furthermore, this technique requires a highly specialized and state of-the-art department of nuclear medicine capable of handling RI sat the point-of-care unit, but most of the public tertiary care centers in developing nations lack this facility. Furthermore, the chance of radiation exposure to the patient and treating surgeon is another significant challenge in the use of radioactive colloid. Hence, the use of diagnostic dyes for SLNB is a viable alternative technique to RI-based methods. Despite the availability of different dyes such as patent blue (PB), isosulfan blue, and indocyanine green, methylene blue (MB) is widely used due to its cost effectiveness and easy availability. Besides, the use of the MB technique alone is practiced more in SLNB these days due to its technical ease of use and lesser chances of anaphylaxis and/or tissue necrosis compared with other dyes (8–10). Despite the wide acceptability of MB in SLND, some surgeons reported quick diffusibility of the dye into the peripheral tissues, which stains a large portion of the breast, thereby affecting the surgical procedure to some extent (11– 13). Similarly, few authors reported varying sensitivity, specificity, sentinel lymph node (SLN) identification rate, and false-negative rate (FNR) of MB dye in SLNB (14–17). It is therefore imperative to validate this economic and cost-effective SLNB technique to increase usage in public healthcare settings in developing nations like India. Hence, the objective of this study was to assess the accuracy of this tracer technique (using MB alone) in clinically and radiologically node-negative breast cancer patients.



Patients and Methods

This study was approved by the institutional ethics committee of Acharya Harihar Regional Cancer Centre, Cuttack, Odisha, India(letter no. 102-IECAHRCC).From January 2018 to February 2020, patients with early invasive female breast cancer (stageT1– T3,N0, M0) with clinically and radiologically nodenegative axilla were included prospectively in this study (n=43).Of 51 identified patients, 3patients with progressive disease with skin involvement and 5 patients in whom SNLs could not be identified were excluded (Figure 1).The details of the 5 cases where SNLs could not be identified are given in Table1. The small sample size precluded any statistical conclusion. Patients with previous breast cancer surgery or axillary dissection, neoadjuvant therapy, distant metastasis, or any palpable or radiologically detected axillary nodes were excluded from the study. Patients with T4 or larger tumors, with inflammatory breast cancer, who were pregnant females, or with male breast cancer were also excluded from this study. Similarly, patients with any scar of previous surgery within the natural pathway of lymphatic drainage that blocks the lymphatics going toward axilla were not included. Patients who received radiation therapy to the chest wall for any other reason, and patients unwilling to participate in the study were also excluded.

In this research, five experienced surgical oncologists participated, and the surgeries were performed after obtaining informed consent from the patients. The surgeries were performed as per standard protocol (18– 20), with minor modifications. Briefly, routine preoperative assessment of surgical fitness, chest radiography, and ultrasonography was performed for all the enrolled patients. Before approximately 15 to 20 minutes of the surgery or immediately after the induction of anesthesia, 1% MB dye (3–5 mL based on breast volume) was injected in two equally divided doses. Half of the dose was administered in the peritumoral region close to the axilla, while the other half was administered to the periareolar site. Postinjection, for 2 to 5 minutes, gentle message was performed laterally to the tumor to prevent the migration of malignant cells to regional lymph nodes and to facilitate the movement of the MB dye. Mastectomy or lumpectomy was performed with standard principles, and then, the axilla was exposed. The axilla was accessed by a separate axillary incision, and the lateral and anterior skin flaps were raised, up to the angular vein, as in standard methodology in the case of breastconserving surgery planning. When modified radical mastectomy was planned, the axilla was accessed through the same incision after raising the skin flaps laterally and anteriorly. Starting from the axillary tail of Spence, the blue lymphatics were searched and traced toward the nearest node. Then, the lymph nodes in the axillary tail; pectoral, central, lateral, and posterior groups; and interpectoral and apical nodes were searched meticulously in situ for blue-stained ones. Simultaneously, the axilla was palpated during surgery for the presence of any suspicious nodes (nodes >1cm or with rounded shape) harboring metastatic disease. The nodes that stained blue completely or partially (Figure2 VI, VII) and suspicious nodes were considered as SLN and were harvested. Furthermore, level I and II nodal dissection were done, followed by level III lymphadenectomy, and sent for histopathology in separately labeled containers. Hematoxylin and eosinstained slides of SLNs and all ALNs were carefully studied and compared for the presence or absence of metastasis.

The surgical plan was made on clinical grounds of operability, that is, disease stage and immunohistochemistry (IHC) were not considered in the pre-operative decision making and, thus, were not considered in our study.