The success of a sentinel lymph node (SLN) biopsy is dependent on an interdisciplinary relationship between nuclear medicine, surgery, and pathology. Lymphoscintigraphy after injection of the radiocolloid agent is important not only for the identification of the SLN within the draining basin but also for the identification of potentially involved nodal basins. A number of vital blue dyes have been used for lymphatic mapping in conjunction with a radiocolloid agent. Identification of micrometastases is dependent on a thorough pathologic assessment, including serial sections and immunohistochemistry.
Preoperative lymphoscintigraphy is typically performed in the nuclear medicine department preoperatively to allow for surgical planning. Lymphatic drainage from the site of a primary melanoma can be variable, especially in the head and neck or truncal regions. Drainage to multiple nodal basins may be identified, and lymphoscintigraphy should be used to guide the appropriate biopsy of all involved nodal basins and to guide the intraoperative identification of interval (in-transit) nodes, which can be the only site of nodal metastases.
A four-point intradermal injection of 0.05–1 mCi of technetium 99-labeled sulfur colloid (99mTc-sulfur colloid) at the primary melanoma site is administered at the time of preoperative lymphoscintigraphy. Real-time images are then obtained to visualize the nodal basins. Most centers perform the lymphoscintigram on the day of surgery. There is enough sufficient residual radioactivity to detect an SLN several hours later because of the 6-hour half-life of 99mTc-sulfur colloid.
When the primary tumor is close to the nodal basin (especially in the neck), it may be difficult to determine the discrete drainage pattern. In these cases, additional anatomic views can assist in separating the radioactivity in the nodal basin from that of the primary tumor injection.
Radio colloid agents: there is variation in the radiocolloids used across institutions. 99mTc-sulfur colloid is used in the United States; 99mTc-nanocolloid and 99mTc-antimony trisulphide colloidal preparations are used in many centers outside the United States. In general, the smaller the particle size, the faster it will travel and the greater the number of nodes demonstrated. It is for this reason that many institutions in the United States filter the colloidal preparation before dispensing through a 0.22-micron filter to ensure a more consistent particle size in the injectate. Intradermal injection is preferred by most centers, because this most closely mimics the potential passage of malignant cells. Insufficient tissue tension after injection (as may be seen with a subcutaneous injection) will lead to a delay in drainage. To avoid compressing the dermal lymphatics, it is important that injected volumes are kept quite small, with volumes of approximately 0.1 mL preferred. Of note, tilmanocept (Lymphoseek; Navidea Biopharmaceuticals, Dublin, OH) is a lymphatic mapping agent that is under development and has been tested in phases II (Leong SP, Kim J, Ross M, et al.: Ann Surg Oncol 18:961–969, 2011) and III trials (Cope FO, Sondak VK, Wallace AM: J Clin Oncol 29:532s, 2011 [suppl; abstr LBA8526]).
Radiation safety aspects: both gamma cameras and gamma probes are exquisitely sensitive, such that very small amounts of radioactivity are needed to perform the procedure successfully. Doses administered range from 0.05 to 1 mCi. These doses are approximately 1/20 of the dose given for a typical 99mTc-MDP bone scan. It has been estimated that the dose to a surgeon’s finger from a single SLN surgery is 1/30 of the yearly whole-body absorbed dose from background radiation (Alazraki N, Glass EC, Castronovo F, et al.: J Nucl Med 43:1414–1418, 2002).
Imaging: almost all centers perform gamma camera imaging before surgery in patients with melanoma after injection of radiocolloids to define involved nodal basins. This is particularly the case in distal upper and lower limb melanomas in which an epitrochlear or popliteal node may be involved, truncal melanomas in which contralateral rather than ipsilateral nodal basins are found to be involved, and head and neck melanomas in which pre-auricular, intraparotid, or suboccipital nodes may be involved before nodes in the cervical chain or supraclavicular fossa are involved.
Many centers perform dynamic imaging to determine nodes that receive direct lymphatic drainage. If dynamic imaging is not performed, there is a risk that an end-on lymphatic channel may be misidentified as a node on a single planar image. There are a variety of approaches to assist in the localization of nodes, including the use of cobalt-57 flood sources to outline the body’s anatomy, external outlining of the body’s surface using a hot source that is traced over the body’s surface, and use of hybrid low-dose single-photon emission computed tomography (SPECT-CT) imaging (Even-Sapir E, Lerman H, Lievshitz G, et al.: J Nucl Med 44:1413–1420, 2003). Many centers perform skin marking to identify nodes involved. If this is done, it should be performed in the expected operative position.
Head and neck melanomas should be evaluated with a SPECT-CT device whenever possible, because the combination of the anatomy demonstrated by the CT and SPECT images of the colloid allows very precise localization of the nodes demonstrated as well as the identification of nodes immediately adjacent to the injection site. These images can assist in the planning of the surgical incision/approach and have been shown to alter the surgical approach in between 20 and 50 % of patients compared with planar imaging (Bilde A, Von Buchwald C, Mortensen J, et al.: Acta Otolaryngol 126:1096–1103, 2006; Vermeeren L, Valdés Olmos RA, Klop WM, et al.: Head Neck 33:1–6, 2011). As with any presurgical planning, good communication between the surgeon and imaging team is essential.
Technical Details of SLN Biopsy
Intraoperative lymphatic mapping and SLN biopsy are routinely performed with both preoperative 99mTc-sulfur colloid injection, which can be detected with a handheld gamma probe and vital blue dye. In the operating room, 1–2 mL of vital blue dye is injected intradermally at the primary tumor site. Successful delivery of the dye intradermally is important, because a subcutaneous injection into the fat may not enable adequate uptake of the radioactive tracer or dye by the cutaneous lymphatic channels. The injection of blue dye is routinely performed before sterile preparation of the patient operative sites to allow 5–10 min for the dye to reach the lymph node basin.
The commercially available vital blue dyes in the United States include isosulphan blue (Lymphazurin; Tyco Healthcare Group, Norwalk, CT) and methylene blue dye. Both blue dyes are effective for lymphatic mapping but have unique side effect profiles (Liu Y, Truini C, Ariyan S: Ann Surg Oncol 15:2412–2417, 2008; Blessing WD, Stolier AJ, Teng SC, et al.: Am J Surg 184:341–345, 2002; Simmons R, Thevarajah S, Brennan MB, et al.: Ann Surg Oncol. 10:242–247, 2003). Allergic reactions, including anaphylactic reactions, have been reported with the use of isosulphan blue. In a review of 1,835 patients injected with isosulphan blue dye for a variety of surgical procedures, 1.5 % of patients had an adverse reaction (Daley MD, Norman PH, Leak JA, et al.: J Clin Anesth 16:332–341, 2004). The majority of these patients experienced minor events (e.g, skin wheals, itching, and localized edema), but 0.75 % suffered a major anaphylactic reaction (hypotension) while under anesthesia. No deaths have been reported from any of these reactions.
Methylene blue has been associated with tissue necrosis and should be used with care at surgical sites where the majority of the blue dye will not be surgically resected (e.g, face, periorbital, wrists, or ankles). Some have diluted the blue dye to decrease risk of tissue necrosis. Small amounts of residual blue dye may persist after wide local excision (WLE) of the primary site, rarely resulting in a permanent tattoo even if the dye is unable to be totally resected. In addition, because of systemic accumulation, the blue dye will be seen in urine, stool, and lactating breasts for the first 24–36 h after injection.
The handheld gamma probe is used to identify areas of focal radiotracer uptake in the nodal basins identified on preoperative lymphoscintigraphy. A small incision is made in the nodal basin, taking into consideration the incision necessary if completion lymph node dissection is subsequently required. Surgeons trace the blue lymphatic channels or follow the path of radioactivity into the SLN. Electrocautery is used to dissect away the surrounding fatty tissue. Blue lymphatic channels and vascular structures are ligated, and care is taken to not disrupt or cauterize the capsule of the SLN.
After each SLN is removed, it is checked ex vivo to document the radioactive counts per second, and the nodal basin is rescanned with the gamma probe. In general, any lymph nodes that are blue, any lymph nodes with radioactive counts ≥10 % of the ex vivo count of the most radioactive SLN, and any palpably suspicious nodes are removed (McMasters KM, Reintgen DS, Ross MI, et al.: Ann Surg Oncol. 8:192–197, 2001). There is an average of one to three SLNs per nodal basin. If there is concern of background radiation or shine through from the primary melanoma site, WLE can be performed beforehand to decrease radiotracer activity at this site.
Concomitant WLE and sentinel lymphadenectomy are preferred. However, in patients who have undergone previous WLE, the procedure is still technically feasible (Ariyan S, Ali-Salaam P, Cheng DW, et al.: Ann Surg Oncol 14:2377–2383, 2007; Evans HL, Krag DN, Teates CD, et al.: Ann Surg Oncol 10:416–425, 2003; Kelemen PR, Essner R, Foshag LJ, et al.: J Am Coll Surg 189:247–252, 1999; Leong WL, Ghazarian DM, McCready DR: J Surg Oncol 82:143–146, 2003; McCready DR, Ghazarian DM, Hershkop MS, et al.: Can J Surg 44:432–434, 2001). In a study of 104 patients at the University of Texas MD Anderson Cancer Center (Houston, TX) who underwent sentinel lymphadenectomy after previous WLE, the SLN positivity rate was similar to that of more than 1,000 patients who had concomitant WLE and SLN removal during the same time period (Gannon CJ, Rousseau DL Jr, Ross MI, et al.: Cancer 107:2647–2652, 2006). However, because extensive resection can alter lymphatic draining and may not accurately reflect the pathologic status of the draining lymph node basin, removal of the SLN at the time of primary WLE is preferred whenever possible.