Enhancing Sentinel Lymph Node Localization in Head and Neck Melanoma: An Adjunctive Role for Indocyanine Green Fluorescence

Sentinel lymph node biopsy (SLNB) remains a cornerstone in the management of cutaneous melanoma, providing critical staging information that guides prognosis and adjuvant therapy decisions. The standard approach employs preoperative lymphoscintigraphy with technetium-99m radiocolloid and intraoperative gamma probe localization.^1-2 In most cases, this dual-modality strategy reliably identifies the sentinel basin and facilitates precise nodal excision.

However, failure of sentinel node localization remains a recognized and clinically challenging scenario—whether due to absent radiotracer migration on lymphoscintigraphy, suboptimal injection timing or technique, or low intraoperative gamma counts insufficient to distinguish sentinel nodes from background activity. Reported rates of sentinel node non-localization in head and neck melanoma range from approximately 2–10%, with higher rates observed in anatomically complex regions and in patients with prior surgical disruption of lymphatic pathways.³ Non-localization refers to failure to identify a sentinel node on imaging or intraoperatively, whereas low-uptake cases involve identifiable basins with insufficient gamma signal to guide precise dissection.

Non-localization arises from both technical and anatomic factors. Injection depth and timing, altered lymphatic drainage following prior surgery, and tumor-related lymphatic obstruction may impair tracer migration. In the head and neck, proximity of the primary lesion to regional nodal basins can produce a significant “shine-through” effect, in which residual activity from the injection site obscures gamma probe discrimination.³ Even when a basin is identified on preoperative imaging, intraoperative counts may be marginal, necessitating broader dissection to ensure accurate node retrieval.

Blue dyes such as methylene blue have historically served as adjuncts to radiocolloid mapping, yet important limitations persist. Visualization requires direct exposure of lymphatic channels or nodes, meaning localization begins only after incision. Diffusion into surrounding tissues may obscure surgical planes, and staining at the primary site can reduce operative clarity. Moreover, blue dyes provide no pre-incision guidance and offer limited utility when the radiotracer signal is weak.

Indocyanine green (ICG) fluorescence imaging offers several distinct advantages in these challenging circumstances. Following injection, ICG rapidly migrates along lymphatic channels and can be detected using near-infrared imaging systems. In some cases, fluorescence is visible transcutaneously, permitting pre-incision localization and enabling a more precise incision directly over the fluorescent signal. This “fluorescent shine-through” may be particularly valuable in the head and neck, where minimizing incision size and avoiding critical neurovascular structures is paramount.

Unlike radiocolloid mapping, which provides a static signal, ICG enables dynamic, real-time visualization of lymphatic flow using near-infrared imaging, with tissue penetration of approximately 5–10 mm allowing for transcutaneous detection in select cases. Intraoperatively, ICG provides real-time visualization of lymphatic channels and nodal uptake, offering visual confirmation that complements equivocal gamma probe findings.

Compared with blue dyes, ICG provides superior tissue contrast under near-infrared imaging, avoids permanent skin tattooing, and causes less distortion of the operative field. While blue dyes can obscure fascial planes, ICG preserves operative clarity. Systematic reviews and meta-analyses have demonstrated identification rates comparable to radiocolloid and superior to blue dye alone.⁴⁻⁶ Allergic reactions are rare, and the learning curve is modest in centers already equipped with near-infrared platforms. Importantly, ICG does not interfere with radiocolloid mapping and can be used synergistically to enhance localization when gamma counts are low.

Limitations of ICG include limited penetration depth in patients with thicker soft tissue envelopes, dependence on near-infrared imaging platforms, and variability in institutional experience. While short-term identification rates are well supported in the literature, long-term oncologic outcome data directly comparing fluorescence-guided SLNB with conventional radiocolloid-based techniques remain limited. Further prospective studies are needed to define its optimal role within standardized SLNB algorithms.

Although ICG does not replace the anatomic roadmap provided by preoperative lymphoscintigraphy, it represents a valuable adjunct. In cases of non-localizing—where procedures may otherwise be deferred—or low-uptake SLNB—where intraoperative localization is challenging—fluorescence guidance may reduce operative uncertainty, limit unnecessary tissue dissection, and improve procedural efficiency. As near-infrared imaging becomes increasingly integrated into head and neck surgical practice, incorporation of ICG into SLNB algorithms may improve localization accuracy, reduce operative morbidity, and enhance surgical efficiency, particularly in anatomically complex cases.

References

1. Tanis PJ, Nieweg OE, Valdés Olmos RA, Th Rutgers EJ, Kroon BB. History of sentinel node and validation of the technique. Breast Cancer Res. 2001;3(2):109-12. doi: 10.1186/bcr281. Epub 2001 Jan 23. PMID: 11250756; PMCID: PMC139441.
2. Allard-Coutu A, Dobson V, Schmitz E, Shah H, Nessim C. The Evolution of the Sentinel Node Biopsy in Melanoma. Life. 2023; 13(2):489.
3. Stadelmann WK, Cobbins L, Lentsch EJ. Incidence of nonlocalization of sentinel lymph nodes using preoperative lymphoscintigraphy in 74 consecutive head and neck melanoma and Merkel cell carcinoma patients. Ann Plast Surg. 2004 Jun;52(6):546-9; discussion 550. doi: 10.1097/01.sap.0000123810.09847.83. PMID: 15166975.
4. Izzo S, Molle M, Gesuete FP, De Intinis C, Izzo P, Izzo L, Nicoletti GF. Comparison of Different Techniques for the Assessment of Sentinel Lymph Node Biopsy in Melanoma: A Systematic Review. Plast Reconstr Surg Glob Open. 2023 Dec 22;11(12):e5447. doi: 10.1097/GOX.0000000000005447. PMID: 38145154; PMCID: PMC10745233.
5. Lavy D, Shimonovitz M, Keidar D, Warshavsky A, Lessing Y, Abu-Abeid A, Schneebaum S, Miodovnik M, Nizri E. ICG-guided sentinel lymph node biopsy in melanoma is as effective as blue dye: A retrospective analysis. Surg Oncol. 2024 Dec;57:102167. doi: 10.1016/j.suronc.2024.102167. Epub 2024 Nov 19. PMID: 39581000.
6. Wölffer M, Liechti R, Constantinescu M, Lese I, Zubler C. Sentinel Lymph Node Detection in Cutaneous Melanoma Using Indocyanine Green-Based Near-Infrared Fluorescence Imaging: A Systematic Review and Meta-Analysis. Cancers (Basel). 2024 Jul 12;16(14):2523. doi: 10.3390/cancers16142523. PMID: 39061163; PMCID: PMC11274776.