Melanoma Biopsies Research Articles

Circulating tumor DNA as a predictive biomarker in Merkel cell carcinoma

Circulating tumor DNA as a predictive biomarker in Merkel cell carcinoma

Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort.

The prognostic impact of tumor-infiltrating lymphocytes (TILs) on outcomes and treatment efficacy for patients with melanoma in the contemporary era remains poorly characterized. Consecutive patientswho underwent wide excision and sentinel lymph node biopsy forcutaneous melanoma 1 mm thick or thicker at a single institution were identified (2006-2019). The patients were stratified based on primary tumor TIL status as brisk (bTILs), non-brisk (nbTILs), or absent (aTILs). Associations between patient factors and outcomes were analyzed using multivariable analysis. Of the 1017patients evaluated, 846(83.2 %) had primary TILs [nbTILs (n = 759, 89.7 %) and bTILs (n = 87, 10.3 %)]. In the multivariable analysis, the patients with any type of TILs had higher rates of regression [odds ratio (OR), 1.86; p = 0.016], lower rates of acral lentiginous histology (OR, 0.22; p < 0.001), and lower rates of SLN positivity (OR, 0.64; p = 0.042) than those without TILs. The multivariable analysis found no association between disease-specific survival and bTILs [hazard ratio (HR), 1.04; p = 0.927] or nbTILs (HR, 0.89; p = 0.683). An association was found between bTILs and recurrence-free survival (RFS) advantage [bTILs (HR 0.46; p = 0.047), nbTILs (HR 0.71; p = 0.088)], with 5-year RFS rates of 84 % for bTILs, 71.8 % for nbTILs, and 68.4 % for aTILs (p = 0.044). For the 114 immune checkpoint blockade (ICB)-naïve patients who experienced a recurrence treated with ICB therapy, no association was observed between progression-free survival and bTILs (HR, 0.64; p = 0.482) or nbTILs (HR, 0.58; p = 0.176). The prognostic significance of primary TILs in the contemporary melanoma era appears complex. Further studies characterizing the phenotype of TILs and their association with regional metastasis and responsiveness to ICB therapy are warranted.

Incisional Biopsy Technique Is Associated With Decreased Overall Survival for Cutaneous Melanoma.

Previous studies examining melanoma biopsy technique have not demonstrated an effect on overall survival. To examine overall survival of patients with cutaneous melanoma diagnosed by shave, punch, incisional, or excisional techniques from the National Cancer Database (NCDB). Melanoma data from the 2004 to 2016 NCDB data set were analyzed. A Cox proportional hazards model was constructed to assess the risk of 5-year all-cause mortality. In total, 42,272 cases of melanoma were reviewed, with 27,899 (66%) diagnosed by shave biopsy, 8,823 (20.9%) by punch biopsy, and 5,550 (13.1%) by incisional biopsy. Both the univariate and multivariate analyses demonstrated that tumors diagnosed by incisional biopsy had significantly (p = .001) lower overall 5-year survival compared with shave techniques (hazard ratio [HR] = 1.140, 95% confidence interval [CI] 1.055 to 1.231). We found no difference (p = .109) between shave and punch biopsy techniques (HR 1.062, 95% CI 0.987-1.142) or between punch and incisional techniques (HR 1.074, 95% CI 0.979-1.177, p = .131). Incisional biopsies were associated with decreased overall 5-year survival in the NCDB. No difference was observed between shave and punch biopsy techniques. These findings support current melanoma management guidelines.

Time interval between diagnostic excision-biopsy of a primary melanoma and sentinel node biopsy: effects on the sentinel node positivity rate and survival outcomes

IntroductionThe optimal time interval between diagnostic excision of a primary cutaneous melanoma and sentinel node (SN) biopsy is unknown. The current study sought to determine whether this interval influenced the SN-positivity rate, recurrence or survival. MethodsData collected from 2004 to 2014 for a Dutch population-based cohort of patients with melanoma who underwent SN biopsy (SNB) within 100 days of initial diagnosis (n = 7660) and for a similarly specified cohort from a large Australian melanoma treatment centre (n = 3478) were analysed. Time to SNB was analysed continuously (in weeks) and categorically (per month). The effects of SNB timing on SN-positivity were assessed using multivariable logistic regression, and its effects on recurrence-free survival (RFS) and overall survival (OS) were assessed using Cox proportional hazard regression analyses. Advanced modelling using a multivariable Cox model with penalised splines for modelling the continuous effects of time to SNB on RFS and OS was also performed. ResultsIn neither the Dutch nor the Australian cohort was there a significant association between time to SNB and SN-positivity in either cohort, nor was there an impact of time to SNB on RFS or OS in either cohort. The spline-based HR curves for RFS and OS confirmed these findings. ConclusionsThe time interval between diagnostic excision of a primary melanoma and SNB did not influence the SN-positivity rate or survival outcomes. This provides reassurance that neither early nor delayed definitive wide excision and SNB will adversely affect prognosis.

Preoperative Ultrasound‐Guided Incisional Biopsy Enhances the Pathological Accuracy of Incisional Biopsy of Cutaneous Melanoma

To assess the feasibility of preoperative ultrasound (US)-guided incisional biopsy through a prospective controlled clinical trial. This was a prospective, double-arm, single-center study of Chinese patients. Thirty patients were enrolled in the study. Fourteen patients received incisional biopsies for which the choice of biopsy area relied on a clinical evaluation, and 16 patients received incisional biopsies for which the choice of biopsy area relied on a US-guided evaluation. The following procedure was used in the US-guided incisional biopsy group: 1) clinical and dermoscopic evaluation of skin lesions; 2) US examination; 3) incisional biopsy; 4) surgical excision; and 5) histopathological examination. The same procedure was used in the non-US-guided group except without US examination. In the non-US-guided group, the mean tumor thicknesses obtained from incisional biopsy and postoperative histopathological examination were 2.1 and 4.1 mm, respectively. Seven melanomas were underestimated by incisional biopsy, resulting in margins narrower than currently recommended. In the US-guided group, the mean tumor thicknesses obtained from US, incisional biopsy, and postoperative histopathological examination were 3.4, 2.9, and 2.7 mm, respectively. In only 3 melanomas was the tumor thickness of the incisional biopsy less than that of the postoperative histopathological examination, demonstrating that US-guided biopsy obtains the maximum thickness area. Preoperative US-guided incisional biopsy can enhance the pathological accuracy of incisional biopsy, which may allow us to better perform surgical excision with safe peripheral surgical margins.

Fluorescence Imaging Using Methylene Blue Sentinel Lymph Node Biopsy in Melanoma.

Fluorescence imaging of sentinel node biopsy in melanoma is a novel method. Both indocyanine green (ICG) and methylene blue (MB) have fluorescent properties. The aim of this study was to present, for the first time in a clinical series of patients, the possible usage of MB as a fluorescent dye for sentinel node biopsy during surgery for melanoma. Twenty patients with skin melanoma, who were candidates for sentinel node biopsy were enrolled in our study. All patients underwent simultaneous use of standard nanocolloid and blue dye. Transcutaneous visualization of the sentinel node, visualization of lymphatic channels as well as sentinel node fluorescent visualization were all measured. We also performed calculations of Signal to Background ratios (SBR). In 15% (3/20) of patients, the fluorescent sentinel node was visible through the skin. The median SBR for the sentinel node visualization by fluorescence was 3.15 (range, 2.7-3.5). Lymphatic channels were visible in lymphatic tissue via fluorescence before visualization by the naked eye in 4 patients (20%). The median SBR ratio was 3.69 (range, 2.7-4.2). Sentinel nodes were visible by fluorescence in 13 cases (65%). The median SBR ratio was 2.49 (range, 1.5-5.7). No factors were found to be associated with fluorescent MB visualization of a sentinel node during biopsy. This is the first clinical study presenting the usefulness of fluorescent sentinel node biopsy in melanoma patients using MB as a fluorophore. Further studies are necessary to provide methods for its' clinical implementation.

Is Tissue Still the Issue? The Promise of Liquid Biopsy in Uveal Melanoma.

Uveal melanoma (UM) is the second most frequent type of melanoma. Therapeutic options for UM favor minimally invasive techniques such as irradiation for vision preservation. As a consequence, no tumor material is obtained. Without available tissue, molecular analyses for gene expression, mutation or copy number analysis cannot be performed. Thus, proper patient stratification is impossible and patients’ uncertainty about their prognosis rises. Minimally invasive techniques have been studied for prognostication in UM. Blood-based biomarker analysis has become more common in recent years; however, no clinically standardized protocol exists. This review summarizes insights in biomarker analysis, addressing new insights in circulating tumor cells, circulating tumor DNA, extracellular vesicles, proteomics, and metabolomics. Additionally, medical imaging can play a significant role in staging, surveillance, and prognostication of UM and is addressed in this review. We propose that combining multiple minimally invasive modalities using tumor biomarkers should be the way forward and warrant more attention in the coming years.

Machine learning directed sentinel lymph node biopsy in cutaneous head and neck melanoma.

The specificity of sentinel lymph node biopsy (SLNB) for detecting lymph node metastasis in head and neck melanoma (HNM) is low under current National Comprehensive Cancer Network (NCCN) treatment guidelines. Multiple machine learning (ML) algorithms were developed to identify HNM patients at very low risk of occult nodal metastasis using National Cancer Database (NCDB) data from 8466 clinically node negative HNM patients who underwent SLNB. SLNB performance under NCCN guidelines and ML algorithm recommendations was compared on independent test data from the NCDB (n=2117) and an academic medical center (n=96). The top-performing ML algorithm (AUC=0.734) recommendations obtained significantly higher specificity compared to the NCCN guidelines in both internal (25.8% vs. 11.3%, p < 0.001) and external test populations (30.1% vs. 7.1%, p < 0.001), while achieving sensitivity >97%. Machine learning can identify clinically node negative HNM patients at very low risk of nodal metastasis, who may not benefit from SLNB.

Melanin concentration maps by label-free super-resolution photo-thermal imaging on melanoma biopsies.

Surgical excision followed by histopathological examination is the gold standard for melanoma screening. However, the color-based inspection of hematoxylin-and-eosin-stained biopsies does not provide a space-resolved quantification of the melanin content in melanocytic lesions. We propose a non-destructive photo-thermal imaging method capable of characterizing the microscopic distribution and absolute concentration of melanin pigments in excised melanoma biopsies. By exploiting the photo-thermal effect primed by melanin absorption of visible laser light we obtain label-free super-resolution far-infrared thermal images of tissue sections where melanin is spatially mapped at sub-diffraction 40-μm resolution. Based on the finite-element simulation of the full 3D heat transfer model, we are able to convert temperature maps into quantitative images of the melanin molar concentration on B16 murine melanoma biopsies, with 4·10-4 M concentration sensitivity. Being readily applicable to human melanoma biopsies in combination with hematoxylin-and-eosin staining, the proposed approach could complement traditional histopathology in the characterization of pigmented lesions ex-vivo.

Sentinel Lymph Node Biopsy vs. Observation in Thin Melanoma: A Multicenter Propensity Score Matching Study.

The therapeutic value of sentinel lymph node biopsy (SLNB) in thin melanoma remains controversial. The aim of this study is to determine the role of SLNB in the survival of thin melanomas (≤1 mm). A multicenter retrospective observational study was designed. A propensity score matching was performed to compare patients who underwent SLNB vs. observation. A multivariate Cox regression was used. A total of 1438 patients were matched by propensity score. There were no significant differences in melanoma-specific survival (MSS) between the SLNB and observation groups. Predictors of MSS in the multivariate model were age, tumor thickness, ulceration, and interferon treatment. Results were similar for disease-free survival and overall survival. The 5- and 10-year MSS rates for SLN-negative and -positive patients were 98.5% vs. 77.3% (p < 0.001) and 97.3% vs. 68.7% (p < 0.001), respectively. SLNB does not improve MSS in patients with thin melanoma. It also had no impact on DSF or OS. However, a considerable difference in MSS, DFS, and OS between SLN-positive and -negative patients exists, confirming its value as a prognostic procedure and therefore we recommend discussing the option of SLNB with patients.

Is Computer-Assisted Tissue Image Analysis the Future in Minimally Invasive Surgery? A Review on the Current Status of Its Applications.

Purpose: Computer-assisted tissue image analysis (CATIA) enables an optical biopsy of human tissue during minimally invasive surgery and endoscopy. Thus far, it has been implemented in gastrointestinal, endometrial, and dermatologic examinations that use computational analysis and image texture feature systems. We review and evaluate the impact of in vivo optical biopsies performed by tissue image analysis on the surgeon’s diagnostic ability and sampling precision and investigate how operation complications could be minimized. Methods: We performed a literature search in PubMed, IEEE, Xplore, Elsevier, and Google Scholar, which yielded 28 relevant articles. Our literature review summarizes the available data on CATIA of human tissues and explores the possibilities of computer-assisted early disease diagnoses, including cancer. Results: Hysteroscopic image texture analysis of the endometrium successfully distinguished benign from malignant conditions up to 91% of the time. In dermatologic studies, the accuracy of distinguishing nevi melanoma from benign disease fluctuated from 73% to 81%. Skin biopsies of basal cell carcinoma and melanoma exhibited an accuracy of 92.4%, sensitivity of 99.1%, and specificity of 93.3% and distinguished nonmelanoma and normal lesions from benign precancerous lesions with 91.9% and 82.8% accuracy, respectively. Gastrointestinal and endometrial examinations are still at the experimental phase. Conclusions: CATIA is a promising application for distinguishing normal from abnormal tissues during endoscopic procedures and minimally invasive surgeries. However, the efficacy of computer-assisted diagnostics in distinguishing benign from malignant states is still not well documented. Prospective and randomized studies are needed before CATIA is implemented in clinical practice.

Curative Intent Surgery of Oral Malignant Melanoma and Regional Lymph Node Biopsy Assessment in 25 Dogs: 2006-2017.

Medical records were searched for dogs that had received curative intent surgery for oral malignant melanoma and ipsilateral excisional regional lymph node biopsy. Twenty-seven dogs were operated on and 25 dogs of these dogs met the inclusion criteria of signalment, post-excision margin status, presence of metastasis for each biopsied lymphocentrum, survival time post-excision, presence of recurrence or metastasis at follow-up or at death/euthanasia, location of the primary tumor, and any postoperative adjuvant treatment. These 25 dogs had complete tumor excision with tumor-free margins and 19 (76%) had postoperative adjuvant therapy. Median survival time after excision for the dogs in this study was 335.5 days. Results of this study support previous work that documents prolonged survival time following complete excision of oral malignant melanoma with tumor-free surgical margins in dogs. Additionally, 4 dogs (16%) had histologically confirmed regional lymph node metastasis at the time of definitive surgery.

Analysis of the Different Lymphatic Drainage Patterns during Sentinel Lymph Node Biopsy for Skin Melanoma

In the last two decades, studies of lymphoscintigraphy imaging in lymphatic mapping reported an extreme heterogeneity of skin lymphatic drainage of some skin area, in contrast with the previous scientific literature. The aim of this study was to investigate the presence of any correlations between the topographical location of cutaneous melanoma and the topographical location of sentinel lymph nodes. Data from 165 patients undergoing sentinel lymph node biopsy between January 2013 and May 2021 were analyzed, demonstrating that melanomas in the Lumbar region presented a significant more heterogeneous drainage by site than those in the Scapular region (p < 0.01) and that melanomas in the Subscapular region were significantly more heterogeneous by laterality (unilateral vs. bilateral) than those in the Scapular region (p < 0.05). Results of this study supported the evidence of multiple lymphatic drainage as regards the sentinel node biopsy performed in skin melanoma located on the dorsal subscapular region and lumbar region. For this reason, the association of preoperative lymphoscintigraphy with another imaging evaluation is needed in these critical cutaneous areas. Recent technical developments enabling fluorescence lymphography together with indocyanine green have significantly improved the visualization of lymphatic drainage patterns at a microscopic level. In the preoperative phase, any doubt can be resolved by associating the SPET-CT scan to lymphoscintigraphy, while during the intraoperative phase, an additional evaluation with indocyanine green can be performed in doubtful cases. The aim of the duplex lymphatic mapping (pre and/or intraoperative) is an accurate search of sentinel nodes, in order to reduce the rate of false negatives.

Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or activate sensory neurons’ firing within the melanoma tumor. Melanoma growth and angiogenesis were accelerated following inhibition of sensory neurons’ activity and were reduced following overstimulation of these neurons. Sensory neuron-specific overactivation also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of melanoma biopsies revealed that increased expression of sensory neurons-related genes within melanoma was associated with improved survival. These findings suggest that sensory innervations regulate melanoma progression, indicating that manipulation of sensory neurons’ activity may provide a valuable tool to improve melanoma patients’ outcomes.

Biopsy for molecular risk stratification in uveal melanoma: Yields and molecular characteristics in 119 patients.

Prognostic cytological and molecular features of uveal melanoma have been well researched and are essential in management. Samples can be obtained in vivo through fine needle aspirate biopsy, vitrector cutter, forceps or post-enucleation for off-site testing. This study aims to examine cytological and chromosome microarray yields of these samples. A retrospective cohort analysis of 119 uveal melanoma biopsies submitted to our laboratory. Samples included those taken in vivo (n=57) and post-enucleation (n=62). Patient and tumour features were collected including age, sex, primary tumour location, basal diameter and tumour height. Prognostic outcomes measured include cell morphology, chromosomal status and immunohistochemistry. Post-enucleation biopsies accounted for just over half of our samples (52%). Post-enucleation samples had a more successful genetic yield than in vivo biopsies (77% vs. 50%, p=0.04) though there was no difference for cytological yields. There was no difference in cytological or microarray yields between instruments. The vitrector biopsy group had the smallest tumour thickness (5 mm vs. 10 mm [fine-needle aspirate biopsy], p=0.003). There was a strong correlation between monosomy 3, BAP1 aberrancy and epithelioid cell type in post-enucleation samples (Tb =0.742, p=0.005). However, epithelioid morphology was not associated with either monosomy 3 (p=0.07) or BAP1 aberrancy (p=0.24) for in vivo biopsies. All three biopsy instruments provide similar cytological yields as post-enucleation sampling, although post-enucleation samples had a more successful chromosome microarray yield. Epithelioid cytomorphology alone is insufficient for prognostication in in vivo biopsies, immunohistochemistry would be a useful surrogate test.

Effectiveness of SPECT/CT Imaging for Sentinel Node Biopsy Staging of Primary Cutaneous Melanoma and Patient Outcomes

PurposeCoregistered SPECT/CT can improve accuracy of sentinel node biopsy (SNB) for staging melanoma. This benefit has implications for pathology services and surgical practice with increased diagnostic and surgical workload. The purpose of this study was to investigate the effectiveness of SPECT/CT imaging.MethodsSNB data were collected over a 10-year period. Preoperative SLN mapping was performed by using planar lymphoscintigraphy (LSG) for all patients (n = 1522) and after October 2015, patients underwent a second co-registered SPECT/CT scan (n = 559). The patients were stratified according to the imaging protocol. The number of nodes and nodal basins were assessed. The reasons for cancellation also were assessed.ResultsA total of 95% (1446/1522) of patients underwent a successful SNB procedure. Significantly more sentinel nodes were identified by the SPECT/CT protocol (3 vs. 2; p < 0.0001). More patients were cancelled in the SPECT/CT cohort (9.3% vs. 2.5%; p < 0.0001). Head & neck, lower limb, and AJCC IB primaries were significantly less likely to proceed to SNB. SPECT/CT identified significantly more positive SNBs (20.9% vs. 16.5%; p = 0.038). SPECT/CT imaging was associated with improved disease-free (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54–1.0); p = 0.048) and disease-specific survival (HR = 0.48; 95% CI: 0.3–0.78; p = 0.003). Patients who did not proceed to SNB had a significantly increased nodal relapse rate (23.5% vs. 6.8%; HR = 3.4; 95% CI: 1.9–6.2; p < 0.0001) compared with those who underwent SNB.ConclusionsThis large cohort study confirms the increased accuracy of SPECT/CT for identifying SLN metastases, which would appear to have a significant therapeutic benefit, although an increased risk of cancellation of the SNB procedure on the day of surgery.

Melanoma sentinel lymph node biopsy and completion lymph node dissection: A regional hospital experience

Completion lymph node dissection (CLND) following positive sentinel lymph node biopsy (SLNB) for cutaneous melanoma is a topic of controversy. The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) suggested no survival benefit with CLND over observation amongst patients with a positive SLNB. The findings of the MSLT-II may have limited applicability to our high-risk population where nodal ultrasound and non-surgical melanoma treatment is rationed. In this regional, retrospective study, we reviewed primary melanoma, SLNB and CLND histopathological reports in the Bay of Plenty District Health Board (BOPDHB) across a 10-year period. The primary outcomes measured were size of sentinel lymph node metastases and non-sentinel node (NSN) positivity on CLND for patients with a positive SLNB. In the 157 SLNB identified, the mean sentinel lymph node metastatic deposit size was larger in BOPDHB compared with MSLT-II (3.53 vs 1.07/1.11mm). A greater proportion of BOPDHB patients (54.8%) had metastatic deposits larger than 1mm compared with MSLT-II (33.2/34.5%) and the rate of NSN involvement on CLND was also higher (23.8% vs 11.5%). These findings indicate that the BOPDHB is a high-risk population for nodal melanoma metastases. Forgoing CLND in the context of a positive SLNB may place these patients at risk.

Identification of Inguinal Sentinel Lymph Nodes in Recurrent Vulvar Melanoma

<h3>Study Objective</h3> To demonstrate the feasibility of inguinal sentinel lymph node detection in recurrent vulvar melanoma using ICG fluorescence technique. <h3>Design</h3> Radical local excision and sentinel lymph node biopsies for recurrent vulvar melanoma. The injection of ICG tracer was followed by visualization of sentinel lymph nodes using an Image1 S Rubina system (Karl Storz, Germany). <h3>Setting</h3> Tertiary hospital. <h3>Patients or Participants</h3> one patient, 17 months after primary surgical excision and sentinel lymph biopsy for vulvar malignant melanoma. <h3>Interventions</h3> Injection of ICG tracer around the border of the lesion. <h3>Measurements and Main Results</h3> Bilateral sentinel nodes were successfully identified and removed. <h3>Conclusion</h3> Detection of sentinel lymph nodes in recurrent vulvar melanoma is feasible. ICG tracer can be considered for sentinel mapping in recurrent vulvar cancer.

1243 Sentinel Lymph Node Biopsy for Melanoma during the COVID-19 Pandemic

AimSentinel lymph node biopsy (SLNB) is an established aspect of the staging process for primary melanoma, with the results dictating future treatment methods. Due to the COVID-19 pandemic no SLNBs were offered to patients with newly diagnosed melanoma at a hospital site in the West Midlands. The aim of this study was to identify the number of patients who missed out on this investigation in order to ascertain how many patients with a potential positive SLNB were missed.MethodA patient list was provided from the dermatology and plastic surgery database, ensuring that all newly diagnosed melanoma patients throughout the period March-May 2020 were included. A retrospective study design was utilised, with all data collected from the computer system at a single hospital site.Results64 patients were provided via the patient list, of which 44 were appropriate for SLNB using the NICE criteria. After detailed reading of the patient notes, 80% (35/44) of patients were provided with a reason why they did not receive a SLNB, however the remaining 20% (9/44) did not have this clearly recorded.ConclusionsA large cohort of patients did not receive a SLNB during the COVID-19 pandemic. Utilising the clinical literature, it can be predicted that around 9 of these patients would have had a SLNB that identified metastasis. These patients have potentially missed out on adjuvant treatment, and the cohort will therefore require follow up to be adapted to reflect this.

Does the pattern of lymphatic drainage influence the risk of nodal recurrence in trunk melanoma patients with negative sentinel lymph node biopsy?

BackgroundThere are conflicting data regarding the prognostic value of the lymphatic basin drainage pattern in melanoma patients and the evidence is scant in the setting of negative sentinel lymph node biopsy. ObjectiveTo investigate whether the pattern of lymphatic basin drainage influences the risk of nodal disease in patients with melanoma of the trunk and negative sentinel lymph node biopsy. MethodsA case series of patients with trunk melanoma and negative sentinel lymph node biopsy was retrospectively evaluated. Clinicopathological features, the pattern of lymphatic drainage and nodal, metastatic, and overall recurrence-free survival were reviewed. ResultsOf the 135 patients included, multiple lymphatic basin drainage was identified in 61 (45.2%). Ten of the 74 (13.5%) patients with single drainage developed nodal recurrence, compared with 2 of the 61 (3.6%) patients with multiple drainages (p = 0.04). Nodal recurrence-free survival was significantly longer in the group with multiple drainages than in the group with single drainage (175.6 vs. 138.7 months; p = 0.04). In multivariate analysis, single drainage was associated with a higher risk of nodal recurrence (HR = 4.54; p = 0.05). No significant differences in metastatic and overall recurrence-free survival were found between groups. Study limitationsRetrospective analysis, single-center study, small sample, detailed histopathologic information not always present. ConclusionsIn patients with trunk melanoma and negative sentinel lymph node biopsy, multiple lymphatic basin drainage may be an independent risk factor for nodal disease recurrence. This factor may help to identify patients with negative sentinel lymph node biopsy with a higher risk of nodal recurrence.