Diagnostic performance and clinical limitations of sentinel lymph node biopsy in head and neck melanoma: a 20-year retrospective cohort study

Diagnostic performance and clinical limitations of sentinel lymph node biopsy in head and neck melanoma: a 20-year retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Diagnostic performance and clinical limitations of sentinel lymph node biopsy in head and neck melanoma: a 20-year retrospective cohort study Lukas Lükewille, Susanne Wiegand, Asita Fazel, Katharina C. Kähler, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9215982/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Purpose : Sentinel lymph node biopsy (SLNB) is a standard procedure for nodal staging in cutaneous melanoma. However, its diagnostic performance in the head and neck region remains limited due to complex lymphatic drainage patterns. This study aimed to evaluate the long-term diagnostic accuracy of SLNB in head and neck melanoma and to analyze anatomical and clinical factors associated with false-negative results. Methods : This retrospective single-center cohort study included patients with cutaneous head and neck melanoma who underwent SLNB between 2002 and 2022. Patients were stratified into two cohorts (2002–2011 and 2012–2022). Detection rates, sensitivity, negative predictive value, and false-negative rates were calculated. Overall survival was analyzed using Kaplan–Meier estimates and compared by log-rank testing. Results : A total of 189 patients were included. Sentinel lymph node detection significantly improved from 78.2% in the earlier cohort to 98.0% in the later cohort (p < 0.0001). Across the combined cohort, SLNB sensitivity was 72.5%, with a false-negative rate of 27.5%. False-negative events predominantly occurred in anatomically complex drainage regions. Sentinel lymph node status was not significantly associated with overall survival (p = 0.627). Conclusions : Despite substantial improvements in detection rates, SLNB in head and neck melanoma demonstrates clinically relevant limitations in diagnostic sensitivity. The observed false-negative rate highlights a risk of understaging, which may affect eligibility for adjuvant systemic therapies. SLNB findings should therefore be interpreted in the context of anatomical risk patterns and integrated into individualized follow-up strategies. The lack of an association between sentinel lymph node status and overall survival may reflect the impact of modern adjuvant systemic therapies and the distinct biological behavior of head and neck melanoma. However, this finding should be interpreted with caution given the limited sample size. These findings underscore the importance of procedural expertise and risk-adapted surveillance in this anatomically complex region. sentinel lymph node biopsy head and neck melanoma lymphatic drainage false-negative rate SPECT/CT Breslow thickness Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Cutaneous melanoma of the head and neck accounts for approximately 20–30% of all melanoma cases and is characterized by distinct biological and anatomical features. Compared with melanomas of the trunk and extremities, head and neck melanomas exhibit more complex lymphatic drainage patterns, higher rates of early nodal involvement, and an overall less favorable prognosis.¹–³ These characteristics contribute to challenges in regional staging and may adversely affect oncologic outcomes. Sentinel lymph node biopsy (SLNB) is an established staging procedure in cutaneous melanoma and provides essential prognostic information.⁴–⁶ In addition to its prognostic value, SLNB plays a pivotal role in guiding therapeutic decision-making, as sentinel lymph node status determines eligibility for adjuvant systemic therapies in patients with resected melanoma.⁷–⁹ While SLNB demonstrates high diagnostic accuracy in most anatomical regions, its performance in the head and neck remains inferior to that reported for melanomas of the trunk and extremities.¹⁰–¹² This limitation is clinically relevant, as inaccurate nodal staging may lead to understaging and potentially affect subsequent treatment strategies. The reduced accuracy of SLNB in the head and neck is multifactorial. Highly variable and frequently overlapping lymphatic drainage pathways complicate preoperative mapping and increase the risk of failing to identify true first-echelon lymph nodes.¹³–¹⁵ In addition, the close anatomical proximity of multiple drainage basins, radiotracer shine-through effects, and the technical complexity of surgical dissection in anatomically crowded regions further compromise reliable sentinel lymph node identification.¹³–¹⁵ As a consequence, false-negative SLNB results occur more frequently in head and neck melanoma than in other anatomical locations, with important implications for staging accuracy and patient management.¹⁶–¹⁸ Over the past two decades, technical advances, most notably the introduction of hybrid imaging modalities such as SPECT/CT, along with increasing procedural standardization, have aimed to improve sentinel lymph node detection in head and neck melanoma.¹⁹–²² Several studies have demonstrated improved localization accuracy with advanced imaging techniques; however, whether these developments have translated into sustained improvements in overall diagnostic performance remains incompletely defined.¹⁹–²² Moreover, the anatomical patterns and underlying mechanisms associated with false-negative SLNB findings remain insufficiently characterized, despite their critical relevance for risk stratification, treatment planning, and follow-up strategies. The present study provides a comprehensive 20-year evaluation of SLNB in patients with head and neck melanoma treated at a single tertiary academic center. By comparing two consecutive cohorts from 2002–2011 and 2012–2022, we assess temporal trends in sentinel lymph node detection rates, lymphatic drainage patterns, nodal metastasis, false-negative mechanisms, and survival outcomes. The aim of this analysis is to define the diagnostic strengths and limitations of SLNB in this anatomically complex region and to identify clinically relevant factors associated with false-negative results MATERIALS AND METHODS A retrospective single-center cohort study was conducted at the Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel. All patients with histologically confirmed cutaneous melanoma of the head and neck who underwent sentinel lymph node biopsy (SLNB) between January 2002 and December 2022 were identified from institutional clinical records. To evaluate temporal changes in diagnostic performance, the study period was divided into two consecutive cohorts. The first cohort (2002–2011) represents an earlier institutional patient group that has been reported previously and was included as a historical reference. The second cohort (2012–2022) reflects a later institutional period characterized by standardized documentation, routine use of advanced imaging modalities, and complete staging information, and constituted the primary dataset for detailed analyses in the present study. Inclusion criteria were the presence of a primary, non-metastatic cutaneous melanoma located within the anatomical boundaries of the head and neck region, performance of SLNB with localization of at least one sentinel lymph node within the head and neck region, and availability of valid informed consent for the use of clinical data within the institutional broad consent framework and the study was approved by the local ethics committee (D 505/22). Exclusion criteria included synchronous or metachronous multiple primary malignant melanomas and incomplete or missing documentation that precluded reliable evaluation of clinical course or nodal status. Patients treated between 2012 and 2022 with complete staging and follow-up information formed the primary cohort for analyses of sentinel lymph node status, diagnostic performance parameters, and survival outcomes. Patients treated between 2002 and 2011 were included for comparative analyses of sentinel lymph node detection rates, lymphatic drainage patterns, and the occurrence of false-negative SLNB events. Sentinel lymph node detection and surgical technique Preoperative lymphatic mapping was performed using peritumoral injections of technetium-99m–labeled nanocolloid. Planar lymphoscintigraphy was used for sentinel lymph node localization throughout the entire study period. In the later study years, hybrid single-photon emission computed tomography combined with computed tomography (SPECT/CT) was increasingly implemented to improve anatomical localization and depth assessment of sentinel lymph nodes. Intraoperative identification of sentinel lymph nodes was performed using a handheld gamma probe. All lymph nodes demonstrating radiotracer uptake of at least 10% of the maximum activity (“hottest node”) were excised. The number of harvested sentinel lymph nodes and their anatomical localization were documented according to the standard cervical neck level classification. Histopathological analysis Excised sentinel lymph nodes were fixed in formalin and processed according to institutional histopathological protocols. Serial sectioning with hematoxylin–eosin staining was performed and supplemented by immunohistochemical analysis using S-100 protein, HMB-45, and Melan-A, as indicated. Sentinel lymph node status was classified as true positive in the presence of histologically confirmed metastatic involvement. Cases were classified as true negative when no metastatic disease was detected in the sentinel lymph node and no subsequent regional nodal recurrence occurred during follow-up. A false-negative result was defined as the development of regional nodal metastasis following an initially negative sentinel lymph node biopsy. Non-sentinel lymph nodes removed during completion neck dissection were documented and analyzed separately. Clinical follow-up and outcome measures Patients underwent regular clinical follow-up examinations and imaging in accordance with current guideline-based recommendations. Information on recurrence patterns, including local, locoregional, and distant recurrence, as well as survival outcomes, was retrieved from electronic medical records. The primary endpoints of the study were sentinel lymph node detection rate, diagnostic sensitivity, false-negative rate, negative predictive value, anatomical distribution of sentinel lymph node drainage patterns, and comparison of tumor characteristics between true-positive, true-negative, and false-negative groups. Secondary endpoints included findings at completion neck dissection and overall survival. Statistical analysis Statistical analyses were performed using IBM SPSS Statistics. Categorical variables were analyzed using Fisher’s exact test or the chi-square test, as appropriate. Continuous variables were compared using the independent samples t-test or the Mann–Whitney U-test, depending on data distribution. Homogeneity of variances was assessed using Levene’s test, and Welch correction was applied when indicated. Diagnostic performance parameters were calculated using standard definitions, including sensitivity (TP / [TP + FN]), false-negative rate (FN / [TP + FN]), and negative predictive value (TN / [TN + FN]). Receiver operating characteristic (ROC) analysis was performed to evaluate the discriminatory performance of Breslow thickness for sentinel lymph node positivity. Survival outcomes were analyzed using Kaplan–Meier estimates. Differences between groups were assessed using the log-rank test, log-rank trend test, and Gehan–Breslow–Wilcoxon test, as appropriate. All statistical tests were two-sided, and a p-value of less than 0.05 was considered statistically significant RESULTS Patient characteristics Between 2012 and 2022, a total of 102 patients underwent sentinel lymph node biopsy (SLNB) for cutaneous melanoma of the head and neck. In 100 patients, at least one sentinel lymph node (SLN) was successfully identified. For analyses dependent on SLN status, only cases with complete pathological evaluation were included, resulting in a final study cohort of 100 patients. The mean age of the study cohort was 66 years (range 26–87). Primary tumors were most frequently located in the facial region (52.9%), followed by the ear (18.6%), the cervical/nuchal/submandibular region (14.7%), and the scalp (13.7%). Mean Breslow thickness was 2.41 mm. For comparative analyses, a historical cohort of 87 patients treated between 2002 and 2011 at the same institution was included. In this cohort, sentinel lymph node detection was successful in 68 patients (78.2%). Comparison between cohorts demonstrated similar demographic characteristics and follow-up duration, indicating good baseline comparability. SLN detection and anatomical distribution Sentinel lymph node detection improved significantly over time. Detection rates increased from 78.2% in the historical cohort (2002–2011) to 98.0% in the contemporary cohort (2012–2022) (Fisher’s exact test, p < 0.0001; odds ratio 13.97; 95% confidence interval 3.37–61.62). In the contemporary cohort (n = 100), SLNs were most frequently identified in the parotid region (30.0%) and cervical level II (28.0%), followed by level I (19.0%), level V (16.0%), level III (4.0%), and level IV (3.0%). Sentinel lymph nodes located in more than one anatomical level were detected in 33.3% of patients. Comparison with the historical cohort revealed a significant shift in lymphatic drainage patterns (Fisher’s exact test, p = 0.0458), characterized by an increased proportion of auricular and parotid drainage pathways and a relative decline in cervical, nuchal, and submandibular drainage regions Total number of patients, number of patients with successful sentinel lymph node (SLN) detection, and corresponding detection rates are shown for the 2002–2011 and 2012–2022 cohorts. SLN detection was significantly higher in the contemporary cohort. Histopathologic findings of SLNs Among the 100 evaluable patients treated between 2012 and 2022, 81 patients (81%) had histologically negative sentinel lymph nodes (true negative). Eleven patients (11%), seven patients (7%), and one patient (1%) had one, two, and four positive sentinel lymph nodes, respectively. No cases with three positive sentinel lymph nodes were observed. Comparison with the historical cohort (2002–2011) showed no significant difference in the distribution of sentinel lymph node positivity when categorized as 0, 1, or ≥ 2 positive nodes (Chi-square test, χ²( 2 ) = 1.95; p = 0.3773). False-negative (FN) SLNB findings Across the combined 20-year dataset (2002–2022), 11 false-negative (FN) SLNB cases were identified, defined as the development of regional nodal metastasis following an initially negative SLNB. Eight false-negative cases occurred in the 2012–2022 cohort and three in the historical cohort. In false-negative cases, subsequent regional nodal metastases showed a distinct anatomical distribution. Cervical level II was the most frequently involved nodal basin (63.6%), followed by level V (18.2%), level I (9.1%), and level III (9.1%). No false-negative cases involved the parotid basin or deep cervical or nuchal nodal regions. Primary tumors associated with false-negative SLNB were predominantly located in the facial region (81.8%). Comparative analyses demonstrated significant differences in nodal localization patterns between groups. In true-positive cases, nodal metastases were more frequently observed in deeper drainage pathways, predominantly cervical level V and cervical/nuchal regions, whereas in true-negative cases the initially identified sentinel lymph nodes were most commonly located in the parotid basin and cervical level II (Fisher’s exact test, p < 0.0001). False-negative cases showed pronounced clustering of subsequent nodal metastases in cervical level II compared with both true-positive cases (p < 0.0001) and true-negative cases (p = 0.036). Tumor characteristics and SLN positivity Mean Breslow thickness differed significantly between true-positive and true-negative cases. True-positive tumors demonstrated a mean Breslow thickness of 3.23 mm (95% confidence interval 2.37–4.10), whereas true-negative tumors showed a mean thickness of 2.31 mm (95% confidence interval 2.01–2.61) (t(154) = 2.46; p = 0.015; η² = 0.038). Receiver operating characteristic analysis confirmed strong discriminative performance of Breslow thickness for sentinel lymph node positivity (area under the curve 0.9815; 95% confidence interval 0.9711–0.9919; p < 0.0001). No significant differences in Breslow thickness were observed between true-positive and false-negative cases (p = 0.536) or between false-negative and true-negative cases (p = 0.411). Shown are the distributions of Breslow thickness in true-positive (orange), true-negative (blue), and false-negative (gray) cases. Neck dissection findings In the 2012–2022 cohort, 17 of 102 patients (16.67%) underwent completion neck dissection. Among these patients, 14 (82.4%) showed no additional metastatic lymph nodes, whereas three patients demonstrated further nodal involvement, with one, two, and eight additional positive lymph nodes, respectively. Of the 18 patients with sentinel lymph node–positive disease during this period, 15 underwent completion neck dissection Metastatic disease and survival outcomes During follow-up, 32 patients (32.7%) developed metastatic disease, including five cases (16%) of local recurrence, 14 cases (44%) of locoregional metastases, and 23 cases (72%) of distant metastases. Combined metastatic patterns were observed in 31% of patients. Primary tumors in patients who developed metastatic disease were most frequently located in the facial region (47%) and the scalp (25%). Kaplan–Meier survival analysis demonstrated no significant association between sentinel lymph node status and overall survival (log-rank test p = 0.627; log-rank trend test p = 0.507; Gehan–Breslow–Wilcoxon test p = 0.670). No significant differences in overall survival were observed between true-positive, true-negative, and false-negative groups. Kaplan–Meier curves illustrate estimated overall survival over the follow-up period stratified by sentinel lymph node status (true negative, true positive, and false negative). No significant difference in overall survival was observed between the three groups (log-rank test, p = 0.627). DISCUSSION This 20-year evaluation of sentinel lymph node biopsy (SLNB) in cutaneous melanoma of the head and neck demonstrates that, despite substantial advances in imaging and procedural standardization, the diagnostic performance of SLNB in this anatomically complex region remains limited. Most notably, while the introduction of hybrid SPECT/CT imaging was associated with a marked increase in sentinel lymph node (SLN) detection rates, sensitivity and false-negative (FN) rates did not show a comparable improvement. These findings highlight that improved detection does not necessarily translate into improved diagnostic accuracy and underscore the multifactorial determinants of SLNB performance in the head and neck.¹⁹–²² A key finding of this study is the significant increase in SLN detection rates in the contemporary cohort (98.0%). Although advances in preoperative imaging contributed to this improvement, detection rates cannot be attributed to imaging alone. Procedural consistency and surgical expertise appear to play a critical role. Approximately 90% of SLNB procedures in the later cohort were performed by a single experienced surgeon, whereas the earlier cohort involved multiple surgeons with varying levels of experience. SLNB in the head and neck is highly operator-dependent, requiring precise interpretation of lymphoscintigraphic findings and meticulous intraoperative exploration. Previous studies have demonstrated that surgeon experience significantly improves SLN detection and reduces variability, particularly in anatomically challenging regions such as the parotid basin and cervical level II.¹³–¹⁵ The near-complete detection rate observed in the contemporary cohort therefore likely reflects the combined effect of improved imaging and a pronounced experienced-surgeon effect. The absence of a corresponding improvement in sensitivity supports the interpretation that detection alone is not sufficient to overcome the intrinsic anatomical complexity of lymphatic drainage in this region. The anatomical distribution of SLNs observed in this study provides further insight into the mechanisms underlying FN outcomes. False-negative cases showed a clear clustering in cervical level II, whereas true-positive cases were more frequently associated with deeper drainage pathways, particularly cervical level V and nuchal regions. Cervical level II represents a region characterized by highly variable and overlapping lymphatic drainage, as well as proximity to the primary injection site, which may result in radiotracer shine-through and hinder accurate localization.¹³–¹⁵ The predominance of facial primaries among FN cases further supports the relevance of this anatomical vulnerability. In contrast, the absence of FN events in the parotid basin suggests that, despite technical challenges, parotid-directed drainage pathways may be more consistently identified when adequately explored. These findings emphasize that anatomical factors, rather than tumor biology alone, play a central role in FN SLNB outcomes. In routine clinical practice, lymphatic mapping is frequently performed after prior excision of the primary tumor, which may alter local lymphatic pathways. While this effect may be negligible in melanomas of the trunk and extremities, even subtle changes in tissue architecture or injection geometry may have greater impact in the anatomically dense head and neck region. In particular, facial melanomas are often initially excised outside specialized centers, potentially introducing additional variability in lymphatic mapping. Although this factor cannot be quantified in the present study, it represents a plausible contributor to the increased FN rates observed and warrants further investigation. Tumor-related factors also influenced SLNB performance. Consistent with previous reports, Breslow thickness was significantly associated with SLN positivity.¹⁶–¹⁸ Importantly, no significant differences in tumor thickness were observed between true-positive and FN cases, indicating that FN results are not primarily driven by tumor biology but rather by anatomical and technical factors. In addition, the higher proportion of metastatic disease observed in scalp and cervical or nuchal melanomas is in line with prior studies describing more aggressive behavior and distinct biological characteristics in these subsites.¹–³ Beyond its prognostic role, SLNB has direct implications for therapeutic decision-making. Sentinel lymph node status determines eligibility for adjuvant systemic therapies, including immune checkpoint inhibitors and targeted therapies, which are recommended from specific AJCC stages onward.⁷–⁹ In this context, false-negative SLNB results may lead to clinically relevant understaging, potentially delaying or precluding the initiation of effective systemic treatment. The diagnostic limitations observed in this study therefore have direct consequences for patient management and underscore the importance of careful interpretation of negative SLNB findings, particularly in high-risk anatomical regions. In the present analysis, SLN status was not associated with overall survival. This finding should be interpreted with caution given the limited sample size. In addition, it likely reflects the evolving treatment landscape, as modern adjuvant and palliative systemic therapies, particularly immune checkpoint inhibitors, have been shown to significantly improve survival outcomes in melanoma.⁷–⁹ These advances may attenuate the prognostic impact of nodal status observed in earlier treatment eras. Furthermore, head and neck melanoma is known to exhibit a higher propensity for early hematogenous dissemination compared with melanomas of other anatomical sites, which may further reduce the relative prognostic significance of regional nodal involvement.¹–³ The interpretation of neck dissection findings must also consider the paradigm shift in surgical management following the results of MSLT-II and DeCOG-SLT.⁴–⁶ Whereas completion lymph node dissection was previously performed routinely in SLN-positive patients, contemporary management favors a risk-adapted approach incorporating tumor burden, number of positive nodes, extracapsular extension, and the feasibility of structured ultrasound surveillance. Accordingly, the low rate of additional nodal metastases observed in this study likely reflects current treatment strategies rather than limitations of SLNB itself. Taken together, these findings have several important clinical implications. First, SLNB remains a valuable staging procedure in head and neck melanoma, but its diagnostic limitations must be explicitly acknowledged, particularly for tumors draining to cervical level II. Second, hybrid SPECT/CT imaging and procedural standardization substantially improve SLN detection and should be considered essential components of contemporary SLNB practice in this region. Third, the risk of false-negative results remains clinically relevant, necessitating risk-adapted postoperative surveillance strategies, especially in patients with facial primaries and negative SLNB findings. Finally, surgical expertise and procedural consistency represent key determinants of diagnostic quality, supporting the centralization of SLNB for head and neck melanoma in specialized, high-volume centers. LIMITATIONS This study has several limitations inherent to its retrospective design. First, although the overall cohort size was substantial, subgroup analyses, particularly for false-negative (FN) cases, were limited by small sample sizes, reducing statistical power and the ability to detect subtle effects. Second, the 20-year study period encompasses significant technological and procedural evolution, most notably the introduction of SPECT/CT imaging. Although the analysis was stratified into two temporal cohorts, residual heterogeneity in diagnostic pathways cannot be fully excluded. Third, the identification of false-negative cases relied on clinical and radiologic follow-up rather than routine histopathological verification, which may underestimate microscopic nodal disease present at the time of SLNB. Fourth, completion neck dissection was not uniformly performed in all SLN-positive patients in the earlier cohort, potentially limiting assessment of the true extent of nodal tumor burden. In addition, detailed quantification of sentinel node tumor burden was not uniformly available across the study period, reflecting evolving pathological reporting standards. This limits a more granular analysis of risk-adapted decision-making for completion neck dissection, particularly in the context of changing therapeutic algorithms. Fifth, as a single-center study, the results reflect local surgical expertise and institutional protocols and may not be fully generalizable to other practice settings. Finally, the inherent anatomical complexity of the head and neck region introduces unavoidable sources of measurement bias. Minor variations in injection technique, imaging interpretation, or intraoperative exposure may influence SLN detection in ways that are difficult to capture in retrospective datasets. Prospective, multicenter studies are therefore warranted to validate the anatomical drainage patterns and false-negative mechanisms identified in the present analysis. CONCLUSION Sentinel lymph node biopsy (SLNB) remains an important staging tool in head and neck melanoma. While advances in imaging and procedural standardization have significantly improved sentinel lymph node detection, diagnostic sensitivity remains limited due to anatomical complexity. False-negative results occur predominantly in specific drainage regions, particularly cervical level II, and may lead to clinically relevant understaging with potential implications for treatment decision-making. Tumor thickness remains a strong predictor of sentinel node positivity but does not distinguish between true-positive and false-negative findings, underscoring the role of anatomical and technical factors. The lack of an association between sentinel lymph node status and overall survival should be interpreted with caution and may reflect both the limited sample size and the impact of modern systemic therapies. These findings highlight the need for careful interpretation of negative SLNB results and support risk-adapted follow-up strategies, particularly in anatomically high-risk regions. Abbreviations AJCC – American Joint Committee on Cancer CT – Computed Tomography FN – False Negative FNR – False Negative Rate HMB-45 – Human Melanoma Black 45 KM – Kaplan–Meier LN – Lymph Node MSLT – Multicenter Selective Lymphadenectomy Trial ND – Neck Dissection NPV – Negative Predictive Value OS – Overall Survival RP / TP – True Positive RN / TN – True Negative S-100 – S-100 protein SLN – Sentinel Lymph Node SLNB – Sentinel Lymph Node Biopsy SPECT/CT – Single-Photon Emission Computed Tomography / Computed Tomography SPSS – Statistical Package for the Social Sciences Declarations Funding: This research received no external funding. Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Medical Faculty of the Christian-Albrechts-University Kiel, Germany (reference number: D 505/22) Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Data Availability Statement: The data supporting the findings of this study are available within the article. The anonymized data generated and analyzed during the current study are available upon reasonable request to qualified researchers. Artificial intelligence (AI) assistance: The authors used a generative AI tool (ChatGPT, OpenAI) solely for linguistic editing (grammar and phrasing). No part of the scientific content, data analysis, or interpretation was generated or altered using AI. All content was reviewed and verified by the authors. Conflicts of Interest: The authors declare no conflict of interest. Author Contribution L.L. conceived the study, performed data collection and statistical analysis, and wrote the main manuscript text.M.H. supervised the project, contributed to study design, and revised the manuscript critically for important intellectual content.C.K. provided dermatological expertise, contributed to the interpretation of the data from a dermatological perspective, and critically revised the manuscript.S.W. contributed scientific input and provided important intellectual guidance for the study.A.F. critically reviewed the manuscript and provided valuable corrections.G.R. collected and analyzed the historical cohort data (2002–2011) used for comparison in this study.All authors reviewed and approved the final manuscript. References Amin MB, Greene FL, Edge SB et al (2017) The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more personalized approach to cancer staging. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9215982","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625752959,"identity":"53f2164e-1519-4e57-91c9-52f1b20bade4","order_by":0,"name":"Lukas Lükewille","email":"","orcid":"","institution":"University Medical Center Schleswig-Holstein","correspondingAuthor":false,"prefix":"","firstName":"Lukas","middleName":"","lastName":"Lükewille","suffix":""},{"id":625752960,"identity":"bf3d5c8d-30ae-4e28-9230-63d5c6f5e7e6","order_by":1,"name":"Susanne Wiegand","email":"","orcid":"","institution":"University Medical Center Schleswig-Holstein","correspondingAuthor":false,"prefix":"","firstName":"Susanne","middleName":"","lastName":"Wiegand","suffix":""},{"id":625752961,"identity":"a1c6ad9f-82d2-400a-bd15-6f9e6e56eae6","order_by":2,"name":"Asita Fazel","email":"","orcid":"","institution":"University Medical Center Schleswig-Holstein","correspondingAuthor":false,"prefix":"","firstName":"Asita","middleName":"","lastName":"Fazel","suffix":""},{"id":625752962,"identity":"41f3d6ec-035d-4c2f-84f4-d50403454668","order_by":3,"name":"Katharina C. Kähler","email":"","orcid":"","institution":"University Medical Center Schleswig-Holstein","correspondingAuthor":false,"prefix":"","firstName":"Katharina","middleName":"C.","lastName":"Kähler","suffix":""},{"id":625752963,"identity":"31abab5c-9106-4c5a-bc60-9953415cee5a","order_by":4,"name":"Guido Radecker","email":"","orcid":"","institution":"University Medical Center Schleswig-Holstein","correspondingAuthor":false,"prefix":"","firstName":"Guido","middleName":"","lastName":"Radecker","suffix":""},{"id":625752964,"identity":"fd275711-9150-4f39-8a37-f2b4c364a2ba","order_by":5,"name":"Markus Hoffmann","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYHACZhCRwMB88AGIIcfAw8DGAEKEtbAlG4AYxqRrSWwgpEW3/exjY54/DHn8bMysG37uuJO+4czxZw8YymxwajE7k26czNvGUCzZxsx2s/fMs9wNZ3vMDRjOpeHWciCN+TBvA0Pihvv9x27wth3O3XCeh02Cse0wbi3nnzEfBjosccMxoC1/2w6nG5xnfwbU8h+3lhtpzMk8bBAtt4G2JBicbTADajmAR8szZsO5bRKJM4F+uS3bdthw5pkzZhIJ55LxOCyNWeLNH5vEfjagw962HZbnO5P+TOJDmR1OLVAggcZPIKRhFIyCUTAKRgFeAAB3EVYTEGVYigAAAABJRU5ErkJggg==","orcid":"","institution":"University Medical Center Schleswig-Holstein","correspondingAuthor":true,"prefix":"","firstName":"Markus","middleName":"","lastName":"Hoffmann","suffix":""}],"badges":[],"createdAt":"2026-03-24 20:53:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9215982/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9215982/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107450974,"identity":"a05b5161-5db1-4dcb-b1f0-4073b1dafd4c","added_by":"auto","created_at":"2026-04-21 15:15:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":46129,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSentinel lymph node detection by study period.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTotal number of patients, number of patients with successful sentinel lymph node (SLN) detection, and corresponding detection rates are shown for the 2002–2011 and 2012–2022 cohorts. SLN detection was significantly higher in the contemporary cohort.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9215982/v1/8986cfd5004fb4a0c1e4b649.png"},{"id":107488633,"identity":"f7ea9d82-5da2-40c0-9451-a3846d09eb97","added_by":"auto","created_at":"2026-04-22 02:45:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":28941,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBreslow thickness (mm) by sentinel lymph node status\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eShown are the distributions of Breslow thickness in true-positive (orange), true-negative (blue), and false-negative (gray) cases.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9215982/v1/be8f6c184fd71df6784f63ca.png"},{"id":107868309,"identity":"ee7abf19-fc76-4606-b0f4-991e8f26938c","added_by":"auto","created_at":"2026-04-27 07:09:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":86469,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier analysis of overall survival by sentinel lymph node status.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaplan–Meier curves illustrate estimated overall survival over the follow-up period stratified by sentinel lymph node status (true negative, true positive, and false negative). No significant difference in overall survival was observed between the three groups (log-rank test, p = 0.627).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9215982/v1/a53a2293e724bef3faa8a8da.png"},{"id":108181062,"identity":"f335f573-3f11-449f-8869-b7eaaf00a313","added_by":"auto","created_at":"2026-04-30 08:56:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":310148,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9215982/v1/67781f19-d84b-474a-8152-1aefcf317bd7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic performance and clinical limitations of sentinel lymph node biopsy in head and neck melanoma: a 20-year retrospective cohort study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCutaneous melanoma of the head and neck accounts for approximately 20\u0026ndash;30% of all melanoma cases and is characterized by distinct biological and anatomical features. Compared with melanomas of the trunk and extremities, head and neck melanomas exhibit more complex lymphatic drainage patterns, higher rates of early nodal involvement, and an overall less favorable prognosis.\u0026sup1;\u0026ndash;\u0026sup3; These characteristics contribute to challenges in regional staging and may adversely affect oncologic outcomes.\u003c/p\u003e \u003cp\u003eSentinel lymph node biopsy (SLNB) is an established staging procedure in cutaneous melanoma and provides essential prognostic information.⁴\u0026ndash;⁶ In addition to its prognostic value, SLNB plays a pivotal role in guiding therapeutic decision-making, as sentinel lymph node status determines eligibility for adjuvant systemic therapies in patients with resected melanoma.⁷\u0026ndash;⁹ While SLNB demonstrates high diagnostic accuracy in most anatomical regions, its performance in the head and neck remains inferior to that reported for melanomas of the trunk and extremities.\u0026sup1;⁰\u0026ndash;\u0026sup1;\u0026sup2; This limitation is clinically relevant, as inaccurate nodal staging may lead to understaging and potentially affect subsequent treatment strategies.\u003c/p\u003e \u003cp\u003eThe reduced accuracy of SLNB in the head and neck is multifactorial. Highly variable and frequently overlapping lymphatic drainage pathways complicate preoperative mapping and increase the risk of failing to identify true first-echelon lymph nodes.\u0026sup1;\u0026sup3;\u0026ndash;\u0026sup1;⁵ In addition, the close anatomical proximity of multiple drainage basins, radiotracer shine-through effects, and the technical complexity of surgical dissection in anatomically crowded regions further compromise reliable sentinel lymph node identification.\u0026sup1;\u0026sup3;\u0026ndash;\u0026sup1;⁵ As a consequence, false-negative SLNB results occur more frequently in head and neck melanoma than in other anatomical locations, with important implications for staging accuracy and patient management.\u0026sup1;⁶\u0026ndash;\u0026sup1;⁸\u003c/p\u003e \u003cp\u003eOver the past two decades, technical advances, most notably the introduction of hybrid imaging modalities such as SPECT/CT, along with increasing procedural standardization, have aimed to improve sentinel lymph node detection in head and neck melanoma.\u0026sup1;⁹\u0026ndash;\u0026sup2;\u0026sup2; Several studies have demonstrated improved localization accuracy with advanced imaging techniques; however, whether these developments have translated into sustained improvements in overall diagnostic performance remains incompletely defined.\u0026sup1;⁹\u0026ndash;\u0026sup2;\u0026sup2; Moreover, the anatomical patterns and underlying mechanisms associated with false-negative SLNB findings remain insufficiently characterized, despite their critical relevance for risk stratification, treatment planning, and follow-up strategies.\u003c/p\u003e \u003cp\u003eThe present study provides a comprehensive 20-year evaluation of SLNB in patients with head and neck melanoma treated at a single tertiary academic center. By comparing two consecutive cohorts from 2002\u0026ndash;2011 and 2012\u0026ndash;2022, we assess temporal trends in sentinel lymph node detection rates, lymphatic drainage patterns, nodal metastasis, false-negative mechanisms, and survival outcomes. The aim of this analysis is to define the diagnostic strengths and limitations of SLNB in this anatomically complex region and to identify clinically relevant factors associated with false-negative results\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eA retrospective single-center cohort study was conducted at the Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel. All patients with histologically confirmed cutaneous melanoma of the head and neck who underwent sentinel lymph node biopsy (SLNB) between January 2002 and December 2022 were identified from institutional clinical records.\u003c/p\u003e \u003cp\u003eTo evaluate temporal changes in diagnostic performance, the study period was divided into two consecutive cohorts. The first cohort (2002\u0026ndash;2011) represents an earlier institutional patient group that has been reported previously and was included as a historical reference. The second cohort (2012\u0026ndash;2022) reflects a later institutional period characterized by standardized documentation, routine use of advanced imaging modalities, and complete staging information, and constituted the primary dataset for detailed analyses in the present study.\u003c/p\u003e \u003cp\u003e Inclusion criteria were the presence of a primary, non-metastatic cutaneous melanoma located within the anatomical boundaries of the head and neck region, performance of SLNB with localization of at least one sentinel lymph node within the head and neck region, and availability of valid informed consent for the use of clinical data within the institutional broad consent framework and the study was approved by the local ethics committee (D 505/22). Exclusion criteria included synchronous or metachronous multiple primary malignant melanomas and incomplete or missing documentation that precluded reliable evaluation of clinical course or nodal status.\u003c/p\u003e \u003cp\u003ePatients treated between 2012 and 2022 with complete staging and follow-up information formed the primary cohort for analyses of sentinel lymph node status, diagnostic performance parameters, and survival outcomes. Patients treated between 2002 and 2011 were included for comparative analyses of sentinel lymph node detection rates, lymphatic drainage patterns, and the occurrence of false-negative SLNB events.\u003c/p\u003e \u003cp\u003eSentinel lymph node detection and surgical technique\u003c/p\u003e \u003cp\u003ePreoperative lymphatic mapping was performed using peritumoral injections of technetium-99m\u0026ndash;labeled nanocolloid. Planar lymphoscintigraphy was used for sentinel lymph node localization throughout the entire study period. In the later study years, hybrid single-photon emission computed tomography combined with computed tomography (SPECT/CT) was increasingly implemented to improve anatomical localization and depth assessment of sentinel lymph nodes.\u003c/p\u003e \u003cp\u003eIntraoperative identification of sentinel lymph nodes was performed using a handheld gamma probe. All lymph nodes demonstrating radiotracer uptake of at least 10% of the maximum activity (\u0026ldquo;hottest node\u0026rdquo;) were excised. The number of harvested sentinel lymph nodes and their anatomical localization were documented according to the standard cervical neck level classification.\u003c/p\u003e \u003cp\u003eHistopathological analysis\u003c/p\u003e \u003cp\u003eExcised sentinel lymph nodes were fixed in formalin and processed according to institutional histopathological protocols. Serial sectioning with hematoxylin\u0026ndash;eosin staining was performed and supplemented by immunohistochemical analysis using S-100 protein, HMB-45, and Melan-A, as indicated.\u003c/p\u003e \u003cp\u003eSentinel lymph node status was classified as true positive in the presence of histologically confirmed metastatic involvement. Cases were classified as true negative when no metastatic disease was detected in the sentinel lymph node and no subsequent regional nodal recurrence occurred during follow-up. A false-negative result was defined as the development of regional nodal metastasis following an initially negative sentinel lymph node biopsy. Non-sentinel lymph nodes removed during completion neck dissection were documented and analyzed separately.\u003c/p\u003e \u003cp\u003eClinical follow-up and outcome measures\u003c/p\u003e \u003cp\u003e Patients underwent regular clinical follow-up examinations and imaging in accordance with current guideline-based recommendations. Information on recurrence patterns, including local, locoregional, and distant recurrence, as well as survival outcomes, was retrieved from electronic medical records.\u003c/p\u003e \u003cp\u003eThe primary endpoints of the study were sentinel lymph node detection rate, diagnostic sensitivity, false-negative rate, negative predictive value, anatomical distribution of sentinel lymph node drainage patterns, and comparison of tumor characteristics between true-positive, true-negative, and false-negative groups. Secondary endpoints included findings at completion neck dissection and overall survival.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics. Categorical variables were analyzed using Fisher\u0026rsquo;s exact test or the chi-square test, as appropriate. Continuous variables were compared using the independent samples t-test or the Mann\u0026ndash;Whitney U-test, depending on data distribution. Homogeneity of variances was assessed using Levene\u0026rsquo;s test, and Welch correction was applied when indicated.\u003c/p\u003e \u003cp\u003eDiagnostic performance parameters were calculated using standard definitions, including sensitivity (TP / [TP\u0026thinsp;+\u0026thinsp;FN]), false-negative rate (FN / [TP\u0026thinsp;+\u0026thinsp;FN]), and negative predictive value (TN / [TN\u0026thinsp;+\u0026thinsp;FN]). Receiver operating characteristic (ROC) analysis was performed to evaluate the discriminatory performance of Breslow thickness for sentinel lymph node positivity.\u003c/p\u003e \u003cp\u003eSurvival outcomes were analyzed using Kaplan\u0026ndash;Meier estimates. Differences between groups were assessed using the log-rank test, log-rank trend test, and Gehan\u0026ndash;Breslow\u0026ndash;Wilcoxon test, as appropriate. All statistical tests were two-sided, and a p-value of less than 0.05 was considered statistically significant\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003ePatient characteristics\u003c/p\u003e \u003cp\u003eBetween 2012 and 2022, a total of 102 patients underwent sentinel lymph node biopsy (SLNB) for cutaneous melanoma of the head and neck. In 100 patients, at least one sentinel lymph node (SLN) was successfully identified. For analyses dependent on SLN status, only cases with complete pathological evaluation were included, resulting in a final study cohort of 100 patients.\u003c/p\u003e \u003cp\u003eThe mean age of the study cohort was 66 years (range 26\u0026ndash;87). Primary tumors were most frequently located in the facial region (52.9%), followed by the ear (18.6%), the cervical/nuchal/submandibular region (14.7%), and the scalp (13.7%). Mean Breslow thickness was 2.41 mm.\u003c/p\u003e \u003cp\u003eFor comparative analyses, a historical cohort of 87 patients treated between 2002 and 2011 at the same institution was included. In this cohort, sentinel lymph node detection was successful in 68 patients (78.2%). Comparison between cohorts demonstrated similar demographic characteristics and follow-up duration, indicating good baseline comparability.\u003c/p\u003e \u003cp\u003eSLN detection and anatomical distribution\u003c/p\u003e \u003cp\u003eSentinel lymph node detection improved significantly over time. Detection rates increased from 78.2% in the historical cohort (2002\u0026ndash;2011) to 98.0% in the contemporary cohort (2012\u0026ndash;2022) (Fisher\u0026rsquo;s exact test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; odds ratio 13.97; 95% confidence interval 3.37\u0026ndash;61.62).\u003c/p\u003e \u003cp\u003eIn the contemporary cohort (n\u0026thinsp;=\u0026thinsp;100), SLNs were most frequently identified in the parotid region (30.0%) and cervical level II (28.0%), followed by level I (19.0%), level V (16.0%), level III (4.0%), and level IV (3.0%). Sentinel lymph nodes located in more than one anatomical level were detected in 33.3% of patients.\u003c/p\u003e \u003cp\u003eComparison with the historical cohort revealed a significant shift in lymphatic drainage patterns (Fisher\u0026rsquo;s exact test, p\u0026thinsp;=\u0026thinsp;0.0458), characterized by an increased proportion of auricular and parotid drainage pathways and a relative decline in cervical, nuchal, and submandibular drainage regions\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTotal number of patients, number of patients with successful sentinel lymph node (SLN) detection, and corresponding detection rates are shown for the 2002\u0026ndash;2011 and 2012\u0026ndash;2022 cohorts. SLN detection was significantly higher in the contemporary cohort.\u003c/p\u003e \u003cp\u003eHistopathologic findings of SLNs\u003c/p\u003e \u003cp\u003eAmong the 100 evaluable patients treated between 2012 and 2022, 81 patients (81%) had histologically negative sentinel lymph nodes (true negative). Eleven patients (11%), seven patients (7%), and one patient (1%) had one, two, and four positive sentinel lymph nodes, respectively. No cases with three positive sentinel lymph nodes were observed.\u003c/p\u003e \u003cp\u003eComparison with the historical cohort (2002\u0026ndash;2011) showed no significant difference in the distribution of sentinel lymph node positivity when categorized as 0, 1, or \u0026ge;\u0026thinsp;2 positive nodes (Chi-square test, χ\u0026sup2;(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u0026thinsp;=\u0026thinsp;1.95; p\u0026thinsp;=\u0026thinsp;0.3773).\u003c/p\u003e \u003cp\u003eFalse-negative (FN) SLNB findings\u003c/p\u003e \u003cp\u003e Across the combined 20-year dataset (2002\u0026ndash;2022), 11 false-negative (FN) SLNB cases were identified, defined as the development of regional nodal metastasis following an initially negative SLNB. Eight false-negative cases occurred in the 2012\u0026ndash;2022 cohort and three in the historical cohort.\u003c/p\u003e \u003cp\u003eIn false-negative cases, subsequent regional nodal metastases showed a distinct anatomical distribution. Cervical level II was the most frequently involved nodal basin (63.6%), followed by level V (18.2%), level I (9.1%), and level III (9.1%). No false-negative cases involved the parotid basin or deep cervical or nuchal nodal regions.\u003c/p\u003e \u003cp\u003ePrimary tumors associated with false-negative SLNB were predominantly located in the facial region (81.8%).\u003c/p\u003e \u003cp\u003eComparative analyses demonstrated significant differences in nodal localization patterns between groups. In true-positive cases, nodal metastases were more frequently observed in deeper drainage pathways, predominantly cervical level V and cervical/nuchal regions, whereas in true-negative cases the initially identified sentinel lymph nodes were most commonly located in the parotid basin and cervical level II (Fisher\u0026rsquo;s exact test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). False-negative cases showed pronounced clustering of subsequent nodal metastases in cervical level II compared with both true-positive cases (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and true-negative cases (p\u0026thinsp;=\u0026thinsp;0.036).\u003c/p\u003e \u003cp\u003eTumor characteristics and SLN positivity\u003c/p\u003e \u003cp\u003eMean Breslow thickness differed significantly between true-positive and true-negative cases. True-positive tumors demonstrated a mean Breslow thickness of 3.23 mm (95% confidence interval 2.37\u0026ndash;4.10), whereas true-negative tumors showed a mean thickness of 2.31 mm (95% confidence interval 2.01\u0026ndash;2.61) (t(154)\u0026thinsp;=\u0026thinsp;2.46; p\u0026thinsp;=\u0026thinsp;0.015; η\u0026sup2; = 0.038).\u003c/p\u003e \u003cp\u003eReceiver operating characteristic analysis confirmed strong discriminative performance of Breslow thickness for sentinel lymph node positivity (area under the curve 0.9815; 95% confidence interval 0.9711\u0026ndash;0.9919; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e \u003cp\u003eNo significant differences in Breslow thickness were observed between true-positive and false-negative cases (p\u0026thinsp;=\u0026thinsp;0.536) or between false-negative and true-negative cases (p\u0026thinsp;=\u0026thinsp;0.411).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eShown are the distributions of Breslow thickness in true-positive (orange), true-negative (blue), and false-negative (gray) cases.\u003c/p\u003e \u003cp\u003eNeck dissection findings\u003c/p\u003e \u003cp\u003eIn the 2012\u0026ndash;2022 cohort, 17 of 102 patients (16.67%) underwent completion neck dissection. Among these patients, 14 (82.4%) showed no additional metastatic lymph nodes, whereas three patients demonstrated further nodal involvement, with one, two, and eight additional positive lymph nodes, respectively.\u003c/p\u003e \u003cp\u003eOf the 18 patients with sentinel lymph node\u0026ndash;positive disease during this period, 15 underwent completion neck dissection\u003c/p\u003e \u003cp\u003eMetastatic disease and survival outcomes\u003c/p\u003e \u003cp\u003eDuring follow-up, 32 patients (32.7%) developed metastatic disease, including five cases (16%) of local recurrence, 14 cases (44%) of locoregional metastases, and 23 cases (72%) of distant metastases. Combined metastatic patterns were observed in 31% of patients.\u003c/p\u003e \u003cp\u003ePrimary tumors in patients who developed metastatic disease were most frequently located in the facial region (47%) and the scalp (25%).\u003c/p\u003e \u003cp\u003eKaplan\u0026ndash;Meier survival analysis demonstrated no significant association between sentinel lymph node status and overall survival (log-rank test p\u0026thinsp;=\u0026thinsp;0.627; log-rank trend test p\u0026thinsp;=\u0026thinsp;0.507; Gehan\u0026ndash;Breslow\u0026ndash;Wilcoxon test p\u0026thinsp;=\u0026thinsp;0.670). No significant differences in overall survival were observed between true-positive, true-negative, and false-negative groups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eKaplan\u0026ndash;Meier curves illustrate estimated overall survival over the follow-up period stratified by sentinel lymph node status (true negative, true positive, and false negative). No significant difference in overall survival was observed between the three groups (log-rank test, p\u0026thinsp;=\u0026thinsp;0.627).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis 20-year evaluation of sentinel lymph node biopsy (SLNB) in cutaneous melanoma of the head and neck demonstrates that, despite substantial advances in imaging and procedural standardization, the diagnostic performance of SLNB in this anatomically complex region remains limited. Most notably, while the introduction of hybrid SPECT/CT imaging was associated with a marked increase in sentinel lymph node (SLN) detection rates, sensitivity and false-negative (FN) rates did not show a comparable improvement. These findings highlight that improved detection does not necessarily translate into improved diagnostic accuracy and underscore the multifactorial determinants of SLNB performance in the head and neck.\u0026sup1;⁹\u0026ndash;\u0026sup2;\u0026sup2;\u003c/p\u003e \u003cp\u003eA key finding of this study is the significant increase in SLN detection rates in the contemporary cohort (98.0%). Although advances in preoperative imaging contributed to this improvement, detection rates cannot be attributed to imaging alone. Procedural consistency and surgical expertise appear to play a critical role. Approximately 90% of SLNB procedures in the later cohort were performed by a single experienced surgeon, whereas the earlier cohort involved multiple surgeons with varying levels of experience. SLNB in the head and neck is highly operator-dependent, requiring precise interpretation of lymphoscintigraphic findings and meticulous intraoperative exploration. Previous studies have demonstrated that surgeon experience significantly improves SLN detection and reduces variability, particularly in anatomically challenging regions such as the parotid basin and cervical level II.\u0026sup1;\u0026sup3;\u0026ndash;\u0026sup1;⁵ The near-complete detection rate observed in the contemporary cohort therefore likely reflects the combined effect of improved imaging and a pronounced experienced-surgeon effect. The absence of a corresponding improvement in sensitivity supports the interpretation that detection alone is not sufficient to overcome the intrinsic anatomical complexity of lymphatic drainage in this region.\u003c/p\u003e \u003cp\u003eThe anatomical distribution of SLNs observed in this study provides further insight into the mechanisms underlying FN outcomes. False-negative cases showed a clear clustering in cervical level II, whereas true-positive cases were more frequently associated with deeper drainage pathways, particularly cervical level V and nuchal regions. Cervical level II represents a region characterized by highly variable and overlapping lymphatic drainage, as well as proximity to the primary injection site, which may result in radiotracer shine-through and hinder accurate localization.\u0026sup1;\u0026sup3;\u0026ndash;\u0026sup1;⁵ The predominance of facial primaries among FN cases further supports the relevance of this anatomical vulnerability. In contrast, the absence of FN events in the parotid basin suggests that, despite technical challenges, parotid-directed drainage pathways may be more consistently identified when adequately explored. These findings emphasize that anatomical factors, rather than tumor biology alone, play a central role in FN SLNB outcomes.\u003c/p\u003e \u003cp\u003eIn routine clinical practice, lymphatic mapping is frequently performed after prior excision of the primary tumor, which may alter local lymphatic pathways. While this effect may be negligible in melanomas of the trunk and extremities, even subtle changes in tissue architecture or injection geometry may have greater impact in the anatomically dense head and neck region. In particular, facial melanomas are often initially excised outside specialized centers, potentially introducing additional variability in lymphatic mapping. Although this factor cannot be quantified in the present study, it represents a plausible contributor to the increased FN rates observed and warrants further investigation.\u003c/p\u003e \u003cp\u003eTumor-related factors also influenced SLNB performance. Consistent with previous reports, Breslow thickness was significantly associated with SLN positivity.\u0026sup1;⁶\u0026ndash;\u0026sup1;⁸ Importantly, no significant differences in tumor thickness were observed between true-positive and FN cases, indicating that FN results are not primarily driven by tumor biology but rather by anatomical and technical factors. In addition, the higher proportion of metastatic disease observed in scalp and cervical or nuchal melanomas is in line with prior studies describing more aggressive behavior and distinct biological characteristics in these subsites.\u0026sup1;\u0026ndash;\u0026sup3;\u003c/p\u003e \u003cp\u003eBeyond its prognostic role, SLNB has direct implications for therapeutic decision-making. Sentinel lymph node status determines eligibility for adjuvant systemic therapies, including immune checkpoint inhibitors and targeted therapies, which are recommended from specific AJCC stages onward.⁷\u0026ndash;⁹ In this context, false-negative SLNB results may lead to clinically relevant understaging, potentially delaying or precluding the initiation of effective systemic treatment. The diagnostic limitations observed in this study therefore have direct consequences for patient management and underscore the importance of careful interpretation of negative SLNB findings, particularly in high-risk anatomical regions.\u003c/p\u003e \u003cp\u003eIn the present analysis, SLN status was not associated with overall survival. This finding should be interpreted with caution given the limited sample size. In addition, it likely reflects the evolving treatment landscape, as modern adjuvant and palliative systemic therapies, particularly immune checkpoint inhibitors, have been shown to significantly improve survival outcomes in melanoma.⁷\u0026ndash;⁹ These advances may attenuate the prognostic impact of nodal status observed in earlier treatment eras. Furthermore, head and neck melanoma is known to exhibit a higher propensity for early hematogenous dissemination compared with melanomas of other anatomical sites, which may further reduce the relative prognostic significance of regional nodal involvement.\u0026sup1;\u0026ndash;\u0026sup3;\u003c/p\u003e \u003cp\u003eThe interpretation of neck dissection findings must also consider the paradigm shift in surgical management following the results of MSLT-II and DeCOG-SLT.⁴\u0026ndash;⁶ Whereas completion lymph node dissection was previously performed routinely in SLN-positive patients, contemporary management favors a risk-adapted approach incorporating tumor burden, number of positive nodes, extracapsular extension, and the feasibility of structured ultrasound surveillance. Accordingly, the low rate of additional nodal metastases observed in this study likely reflects current treatment strategies rather than limitations of SLNB itself.\u003c/p\u003e \u003cp\u003eTaken together, these findings have several important clinical implications. First, SLNB remains a valuable staging procedure in head and neck melanoma, but its diagnostic limitations must be explicitly acknowledged, particularly for tumors draining to cervical level II. Second, hybrid SPECT/CT imaging and procedural standardization substantially improve SLN detection and should be considered essential components of contemporary SLNB practice in this region. Third, the risk of false-negative results remains clinically relevant, necessitating risk-adapted postoperative surveillance strategies, especially in patients with facial primaries and negative SLNB findings. Finally, surgical expertise and procedural consistency represent key determinants of diagnostic quality, supporting the centralization of SLNB for head and neck melanoma in specialized, high-volume centers.\u003c/p\u003e"},{"header":"LIMITATIONS","content":"\u003cp\u003eThis study has several limitations inherent to its retrospective design. First, although the overall cohort size was substantial, subgroup analyses, particularly for false-negative (FN) cases, were limited by small sample sizes, reducing statistical power and the ability to detect subtle effects. Second, the 20-year study period encompasses significant technological and procedural evolution, most notably the introduction of SPECT/CT imaging. Although the analysis was stratified into two temporal cohorts, residual heterogeneity in diagnostic pathways cannot be fully excluded. Third, the identification of false-negative cases relied on clinical and radiologic follow-up rather than routine histopathological verification, which may underestimate microscopic nodal disease present at the time of SLNB. Fourth, completion neck dissection was not uniformly performed in all SLN-positive patients in the earlier cohort, potentially limiting assessment of the true extent of nodal tumor burden. In addition, detailed quantification of sentinel node tumor burden was not uniformly available across the study period, reflecting evolving pathological reporting standards. This limits a more granular analysis of risk-adapted decision-making for completion neck dissection, particularly in the context of changing therapeutic algorithms. Fifth, as a single-center study, the results reflect local surgical expertise and institutional protocols and may not be fully generalizable to other practice settings.\u003c/p\u003e \u003cp\u003eFinally, the inherent anatomical complexity of the head and neck region introduces unavoidable sources of measurement bias. Minor variations in injection technique, imaging interpretation, or intraoperative exposure may influence SLN detection in ways that are difficult to capture in retrospective datasets. Prospective, multicenter studies are therefore warranted to validate the anatomical drainage patterns and false-negative mechanisms identified in the present analysis.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eSentinel lymph node biopsy (SLNB) remains an important staging tool in head and neck melanoma. While advances in imaging and procedural standardization have significantly improved sentinel lymph node detection, diagnostic sensitivity remains limited due to anatomical complexity. False-negative results occur predominantly in specific drainage regions, particularly cervical level II, and may lead to clinically relevant understaging with potential implications for treatment decision-making.\u003c/p\u003e \u003cp\u003eTumor thickness remains a strong predictor of sentinel node positivity but does not distinguish between true-positive and false-negative findings, underscoring the role of anatomical and technical factors. The lack of an association between sentinel lymph node status and overall survival should be interpreted with caution and may reflect both the limited sample size and the impact of modern systemic therapies.\u003c/p\u003e \u003cp\u003eThese findings highlight the need for careful interpretation of negative SLNB results and support risk-adapted follow-up strategies, particularly in anatomically high-risk regions.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAJCC \u0026ndash; American Joint Committee on Cancer\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CT \u0026ndash; Computed Tomography\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;FN \u0026ndash; False Negative\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;FNR \u0026ndash; False Negative Rate\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;HMB-45 \u0026ndash; Human Melanoma Black 45\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;KM \u0026ndash; Kaplan\u0026ndash;Meier\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;LN \u0026ndash; Lymph Node\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;MSLT \u0026ndash; Multicenter Selective Lymphadenectomy Trial\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;ND \u0026ndash; Neck Dissection\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;NPV \u0026ndash; Negative Predictive Value\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;OS \u0026ndash; Overall Survival\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;RP / TP \u0026ndash; True Positive\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;RN / TN \u0026ndash; True Negative\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;S-100 \u0026ndash; S-100 protein\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;SLN \u0026ndash; Sentinel Lymph Node\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;SLNB \u0026ndash; Sentinel Lymph Node Biopsy\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;SPECT/CT \u0026ndash; Single-Photon Emission Computed Tomography / Computed Tomography\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;SPSS \u0026ndash; Statistical Package for the Social Sciences\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: This research received no external funding.\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Medical Faculty of the\u0026nbsp;Christian-Albrechts-University Kiel, Germany (reference number: D 505/22)\u003c/p\u003e\n\u003cp\u003eInformed Consent Statement: Informed consent was obtained from all subjects involved in the study.\u003c/p\u003e\n\u003cp\u003eData Availability Statement: The data supporting the findings of this study are available within the article. The anonymized data generated and analyzed during the current study are available upon reasonable request to qualified researchers.\u003c/p\u003e\n\u003cp\u003eArtificial intelligence (AI) assistance: The authors used a generative AI tool (ChatGPT, OpenAI) solely for linguistic editing (grammar and phrasing). No part of the scientific content, data analysis, or interpretation was generated or altered using AI. All content was reviewed and verified by the authors.\u003c/p\u003e\n\u003cp\u003eConflicts of Interest: The authors declare no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL.L. conceived the study, performed data collection and statistical analysis, and wrote the main manuscript text.M.H. supervised the project, contributed to study design, and revised the manuscript critically for important intellectual content.C.K. provided dermatological expertise, contributed to the interpretation of the data from a dermatological perspective, and critically revised the manuscript.S.W. contributed scientific input and provided important intellectual guidance for the study.A.F. critically reviewed the manuscript and provided valuable corrections.G.R. collected and analyzed the historical cohort data (2002\u0026ndash;2011) used for comparison in this study.All authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmin MB, Greene FL, Edge SB et al (2017) The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin 67(2):93\u0026ndash;99\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEggermont AMM, Spatz A, Robert C (2014) Cutaneous melanoma. Lancet 383(9919):816\u0026ndash;827\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarbe C, Amaral T, Peris K et al (2022) European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics\u0026mdash;update 2022. Eur J Cancer 170:236\u0026ndash;255\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarbe C, Amaral T, Peris K et al (2024) European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment\u0026mdash;update 2024. Eur J Cancer 215:115153\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSwetter SM, Tsao H, Bichakjian CK et al (2019) Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol 80(1):208\u0026ndash;250\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorton DL, Wen DR, Wong JH et al (1992) Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127(4):392\u0026ndash;399\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355(13):1307\u0026ndash;1317\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorton DL, Thompson JF, Cochran AJ et al (2014) Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 370(7):599\u0026ndash;609\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaries MB, Thompson JF, Cochran AJ et al (2017) Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med 376(23):2211\u0026ndash;2222\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeiter U, Stadler R, Mauch C et al (2016) Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol 17(6):757\u0026ndash;767\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEggermont AMM, Blank CU, Mandala M et al (2018) Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 378(19):1789\u0026ndash;1801\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeber J, Mandala M, Del Vecchio M et al (2017) Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 377(19):1824\u0026ndash;1835\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChao C, Wong SL, Edwards MJ et al (2003) Sentinel lymph node biopsy for head and neck melanomas. Ann Surg Oncol 10(1):21\u0026ndash;26\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Rosa N, Lyman GH, Silbermins D et al (2011) Sentinel node biopsy for head and neck melanoma: a systematic review. Otolaryngol Head Neck Surg 145(3):375\u0026ndash;382\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanks JE, Kovatch KJ, Ali SA et al (2020) Sentinel lymph node biopsy in head and neck melanoma: long-term outcomes, prognostic value, accuracy, and safety. Otolaryngol Head Neck Surg 162(4):520\u0026ndash;529\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLachiewicz AM, Berwick M, Wiggins CL, Thomas NE (2008) Survival differences between patients with scalp or neck melanoma and those with melanoma of other sites in the SEER program. Arch Dermatol 144(4):515\u0026ndash;521\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpoerl S, Forschner A, Leiter U et al (2021) Head and neck melanoma: outcome and predictors in a population-based cohort study. Head Face Med 17(1):45\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePasha T, Arain Z, Buscombe J et al (2023) Association of complex lymphatic drainage in head and neck cutaneous melanoma with sentinel lymph node biopsy outcomes: a cohort study and literature review. JAMA Otolaryngol Head Neck Surg 149(5):416\u0026ndash;423\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarim RZ, Scolyer RA, Li W et al (2008) False-negative sentinel lymph node biopsies in melanoma may result from deficiencies in nuclear medicine, surgery, or pathology. Ann Surg 247(6):1003\u0026ndash;1010\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiller MW, Vetto JT, Monroe MM et al (2011) False-negative sentinel lymph node biopsy in head and neck melanoma. Otolaryngol Head Neck Surg 145(5):775\u0026ndash;781\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVeenstra HJ, Wouters MW, Kroon BB et al (2011) Less false-negative sentinel node procedures in melanoma patients with experience and proper collaboration. J Surg Oncol 104(5):454\u0026ndash;457\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDowney J, DeVries K, Lano IM et al (2024) False-negative sentinel lymph node biopsy for melanoma: a single-surgeon experience. Can J Surg 67:E337\u0026ndash;E344\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"sentinel lymph node biopsy, head and neck melanoma, lymphatic drainage, false-negative rate, SPECT/CT, Breslow thickness","lastPublishedDoi":"10.21203/rs.3.rs-9215982/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9215982/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003ePurpose\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eSentinel lymph node biopsy (SLNB) is a standard procedure for nodal staging in cutaneous melanoma. However, its diagnostic performance in the head and neck region remains limited due to complex lymphatic drainage patterns. This study aimed to evaluate the long-term diagnostic accuracy of SLNB in head and neck melanoma and to analyze anatomical and clinical factors associated with false-negative results.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eThis retrospective single-center cohort study included patients with cutaneous head and neck melanoma who underwent SLNB between 2002 and 2022. Patients were stratified into two cohorts (2002\u0026ndash;2011 and 2012\u0026ndash;2022). Detection rates, sensitivity, negative predictive value, and false-negative rates were calculated. Overall survival was analyzed using Kaplan\u0026ndash;Meier estimates and compared by log-rank testing.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eA total of 189 patients were included. Sentinel lymph node detection significantly improved from 78.2% in the earlier cohort to 98.0% in the later cohort (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Across the combined cohort, SLNB sensitivity was 72.5%, with a false-negative rate of 27.5%. False-negative events predominantly occurred in anatomically complex drainage regions. Sentinel lymph node status was not significantly associated with overall survival (p\u0026thinsp;=\u0026thinsp;0.627).\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusions\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eDespite substantial improvements in detection rates, SLNB in head and neck melanoma demonstrates clinically relevant limitations in diagnostic sensitivity. The observed false-negative rate highlights a risk of understaging, which may affect eligibility for adjuvant systemic therapies. SLNB findings should therefore be interpreted in the context of anatomical risk patterns and integrated into individualized follow-up strategies. The lack of an association between sentinel lymph node status and overall survival may reflect the impact of modern adjuvant systemic therapies and the distinct biological behavior of head and neck melanoma. However, this finding should be interpreted with caution given the limited sample size. These findings underscore the importance of procedural expertise and risk-adapted surveillance in this anatomically complex region.\u003c/p\u003e","manuscriptTitle":"Diagnostic performance and clinical limitations of sentinel lymph node biopsy in head and neck melanoma: a 20-year retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-21 15:15:34","doi":"10.21203/rs.3.rs-9215982/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"27124851849544056611894911171457935258","date":"2026-04-19T15:20:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-14T08:15:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-13T15:18:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-13T05:17:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cancer Research and Clinical Oncology","date":"2026-04-12T09:33:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"97418be1-0403-4ff3-a052-fb544e06bb7c","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-01T13:39:12+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 15:15:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9215982","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9215982","identity":"rs-9215982","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}