Papillary intralymphatic angioendothelioma (PILA), also known as Dabska tumour, is a rare lymphatic vascular neoplasm classified as a distinct variant of low-grade angiosarcoma. Despite its locally invasive behaviour, PILA generally carries a good prognosis and rarely metastasises, predominantly affecting children and young adults. Fewer than 50 cases have been reported globally, with most arising in the head and neck region. To our knowledge, this is the first documented case of PILA resection using the Mohs micrographic surgery technique. This report describes the presentation, investigation, and surgical management of PILA in a young female patient. Initially referred to the Department following presumed lipoma excision on her chin, histology unexpectedly revealed features consistent with PILA. As the initial margins were uncertain, Mohs micrographic surgery was planned from the outset to ensure complete tumour removal while preserving surrounding tissue. The tumour was excised in two layers, with histological analysis confirming clear margins. In a second stage, due to the tumour's location and complexity, a planned Mohs procedure under general anaesthesia was performed, combined with level 1 neck dissection for access and an anterolateral thigh free flap reconstruction to achieve functional and aesthetic wound closure. The patient has recovered well and remains under regular outpatient surveillance, with no evidence of recurrence at follow-up. This case highlights the utility of Mohs micrographic surgery as a tailored approach for managing PILA and reinforces the need for further case reports to refine surgical protocols and expand our understanding of this rare neoplasm.

Importance:The Melanoma Institute Australia (MIA) sentinel node (SN) metastasis risk calculator provides estimates of positivity for individual patients based on 6 standard clinicopathological parameters and the full 6-parameter model has been externally validated previously using US data. However, given its geographically widespread use, further validation is required to ensure its applicability to other populations. Objective:To further externally validate the MIA SN metastasis risk calculator and increase its precision by refinement of the 95% CIs. Design, Setting, and Participants:A retrospective multicenter cohort study was carried out using data from 4 continents, including the national Danish Melanoma Database and cancer centers in the UK (n = 3), US (n = 2), New Zealand (n = 1), Sweden (n = 1), and Brazil (n = 1). All patients aged 18 years or older who had an SN biopsy performed for an invasive primary cutaneous melanoma and data available on the following parameters: SN status, patient age at diagnosis, Breslow thickness, and melanoma subtype were included (n = 15 731). Available data were also collected on ulceration status, lymphovascular invasion, and the tumor mitotic rate. Data were collected between July 2021 and December 2023, and the analysis was conducted between January 2024 and June 2024. Main Outcomes and Measures:The primary outcome was the area under the curve (AUC) of the receiver operating characteristics for the full (6-parameter) risk prediction model. Secondary outcomes were the AUCs for each country and for the limited models (3-5 parameters), the model calibration, and the recalculated 95% CIs for the models. Decision curve analysis was performed to assess the tool's clinical utility. Results:The whole pooled cohort consisted of 15 731 patients; 4989 had all 6 parameters available. The AUC was 73.0% (95% CI, 70.6%-75.3%) in the subset with all 6 parameters available, and 70.8%, 71.5%, and 70.1% when 1, 2, or 3 optional parameters were missing, respectively. Calibration was excellent, with an intercept and calibration slope of 0.01 (95% CI, -0.02 to 0.03) and 1.03 (95% CI, 0.90-1.16), respectively. The updated 95% CI ranges were substantially tighter, with a median reduction of more than 75%. Conclusions and Relevance:This study found that the MIA SN-positivity calculator performed best with all 6 parameters and has been significantly improved (version 2), with the same risk point estimates but much tighter 95% CIs. These results demonstrated that the calculator was robust, precise, and applicable to geographically widespread melanoma populations.

Background In-transit metastases (ITMs) are challenging to treat because of their heterogenous disease course and chronic, relapsing–remitting nature. Specific factors associated with worse prognosis are poorly understood and not included in current American Joint Committee on Cancer classifications. An ITMs-specific classification system to aid treatment decisions and clinical trial design is lacking. Methods This study involved 142 patients (M 44%, F 56%; median age 70 years [interquartile range 62–77]) with ITMs from a single, cutaneous melanoma. Baseline melanoma and ITMs characteristics, disease progression, and survival outcomes were collected from a prospective database. The primary outcome was disease-specific survival (DSS). A subgroup analysis excluding stage IV disease at diagnosis was performed. Results A longer ITMs-free interval was associated with a longer DSS (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.98–1.00; p = 0.027). A higher number of ITMs and greater Breslow thickness was associated with a shorter DSS (HR 1.25; 95% CI 1.04–1.51; p = 0.020 and HR 1.10; 95% CI 1.04–1.17; p = 0.001). No independent predictors of DSS were identified. On multivariable analysis, larger ITMs and synchronous regional disease correlated with a worse distant metastasis-free survival (HR 1.02; 95% CI 1.03–1.31; p = 0.015 and HR 2.61; 95% CI 1.44–4.72; p = 0.002). Maximum threshold analysis selected the optimal cut-point for continuous variables: two lesions for number of ITMs and 30 mm for size at initial diagnosis, 2 mm for primary melanoma Breslow thickness, and 20 months for ITMs-free interval (time from primary melanoma diagnosis to ITMs onset), adjusted to 18 months for clinical relevance. Conclusion Patients presenting with more than two and/or >30 mm ITMs at first diagnosis, short ITM-free interval (≤18 months), and synchronous regional disease should be considered at higher risk for disease progression and death.

The management of stage III melanoma has undergone profound change with the advent of effective systemic therapies and the growing use of neoadjuvant immunotherapy. This paper highlights the issues raised and points discussed during the Great Debates session at the 2024 SSO Conference in Atlanta, focusing on the necessity of therapeutic lymph node dissection (TLND) after index lymph node (ILN) surgery.

Purpose: To identify consensus-based quality indicators to evaluate melanoma care. Methods: Melanoma quality indicators were identified from a literature review. Twenty-nine indicators in six topic domains were subsequently developed: diagnosis and diagnostic biopsy, patient experience, treatment, pathology, symptom management, survivorship. Clinical experts in melanoma from Ontario and international jurisdictions, representing the disciplines of surgery, pathology, primary care, medical oncology, radiation oncology, and palliative care, in addition to a health system leader, an epidemiologist and a patient and family advisor were invited to participate on the Delphi Panel. Panelists were asked to rate indicators on a nine-point Likert scale for appropriateness. Two iterations of electronic surveys were anonymously completed, followed by a virtual consensus meeting to prioritize quality and outcome melanoma indicators. Results: Twenty-three panel members participated in the modified-Delphi process. Twenty-three quality indicators reflecting high-quality melanoma care across the care continuum were prioritized based on a defined consensus agreement of >= 80 % although only 4 were measurable from current administrative databases. These indicators were assessed for measurement feasibility and four of these were deemed feasible to measure from administrative databases along with eight standard indicators. Conclusion: Melanoma outcome and quality indicators were identified using a modified-Delphi process for inclusion in a provincial cancer system performance report.

Two-dimensional histologic features have demonstrated independent prognostic value for survival in primary cutaneous melanoma, but their predictive value for sentinel node (SN) status has yet to be validated. We aimed to demonstrate the predictive value of the previously described calculated tumor area (CTA), and the novel Simplified Breslow Area (SBA), for SN metastasis and survival. A total of 177 primary melanomas were assessed for standard histological characteristics, maximum invasive width (IW) of the primary tumor and CTA. We simplified CTA measurement by transforming IW with Breslow thickness (BT) [ln(IW) + ln (BT)], yielding SBA. Multivariate analysis was undertaken to assess the performance of CTA and SBA, respectively, as independent predictors of both SN status and survival outcomes. The SN + rate was 18.1

Background PET/CT is widely used in the staging of patients with melanoma groin lymph node (LN) metastases. This study aims to utilise prospectively collected data to determine the accuracy of this modality in the diagnosis of pelvic metastases in those patients with known inguinal LN involvement. Methods Data collected as part of the Evaluation of Groin Lymphadenectomy Extent for Metastatic Melanoma (EAGLE-FM) trial was analysed. Patients with known inguinal LN metastases were evaluated with 18 F-FDG PET/CT. Those without evidence of pelvic LN abnormalities were randomised to inguinal dissection or ilio-inguinal dissection. Those with evidence of abnormality in the pelvic LNs were excluded from the main EAGLE-FM trial but offered ilio-inguinal dissection. Post operative histology results from those patients undergoing ilio-inguinal dissection were analysed to determine the accuracy of PET/CT in the assessment of pelvic LNs. Results There were 101 patients randomised on the EAGLE-FM trial. For this substudy, there were 49 patients who had negative pelvic LNs on PET/CT and 5 patients with positive pelvic nodes on PET/CT included in this analysis. The sensitivity of PET/CT was 25 %, specificity 95.6 % with positive predictive value (PPV) 50.0 % and negative predictive value (NPV) 87.8 %. Conclusion PET/CT has reasonable NPV but poor PPV. While PET/CT is an important modality in the staging of patients with stage III melanoma, it has limited accuracy in the diagnosis of pelvic LN metastases.

BACKGROUND:A retrospective cohort study was undertaken to examine the management of basal cell carcinoma (BCC) in older patients. OBJECTIVES:The aim was to identify subgroups where intervention could be minimised, based on frailty and trends in survival. METHODS:All patients aged 90 years and over with histologically confirmed BCC during 2017 and 2018 were included within the study (n = 319). RESULTS:Age was the most significant predictor of survival (HR=1.10 (95% CIs: 1.04-1.17); p=0.001). Maximum threshold analysis identified 93 years as the significant age cutpoint. Median survival was 40 months for ≤93 years and 28 months for >93 years (p=0.002). Patients with dementia had a worse survival than those without (median survival: 25 months versus 35 months, respectively; HR=1.92 (95% CIs: 1.18-3.13); p=0.009). There was a statistically significant difference in survival for patients who received treatment for their BCC (n=294) compared those observed (n=25) (median survival 34 months versus 21 months, respectively; HR= 0.54 (95% CIs: 0.34-0.85); p=0.007). All other comorbidities examined had no influence on survival. CONCLUSIONS:This study provides evidence in support of active treatment of BCC in individuals aged ≥90 years, seen in secondary care. Conservative options may be preferable in patients with dementia or those >93 years old.

Background: The Melanoma Institute Australia (MIA) sentinel node (SN) metastasis risk-prediction online calculator[Lo2020] is now widely used around the world. The tool comprises eight models that variously use between three and six input parameters. However, the full (six-parameter) model has only been validated in the US population, the model with missing mitoses was validated for the Dutch and Swedish populations. Furthermore, some confidence intervals (CIs) of the tool are large due to uncommon input parameter values. This study further validated the tool in other populations and improved the precision of the risk estimates. Methods: Validation data were pooled from the Danish national Melanoma Database and eight cancer centres: UK(3), US(2), New Zealand(1), Sweden(1), Brazil(1). CI refinement data were pooled from this and previous validation and development cohorts. All patients had the SN result and the minimum data required for the tool (age, Breslow thickness and melanoma subtype), while the presence of ulceration, lymphovascular invasion or mitoses were included where available. The performance of the tool was assessed using C-statistics for discrimination and via a calibration plot. Re-calculation of CIs for the estimated risks was performed using the combined data from all original risk calculator development and validation cohorts. Results: The validation cohort consisted of 15,371 patients, 4,989 of whom had all six input parameters for the full model. The C-statistics were 73.0% (95% CI 70.6–75.3%) in the subset with all six parameters available, Receiver operating characteristic (ROC) curves showing the accuracy (AUC) and confidence intervals (CI) of the Melanoma Institute Australia (MIA) risk calculator to predict sentinel node positivity in the development cohort (black), n=3,477, and the international validation cohort with all six input parameters available (red), n=4,989. and 70.8%, 71.5% and 70.1% when 1, 2 or 3 optional parameters were missing. Calibration was excellent, with an intercept and calibration slope of 0.01 (95% CI -0.02–0.03) and 1.03 (95% CI 0.90–1.16), respectively. The revised CIs were substantially smaller than in the original tool, with a median reduction of over 75%. Conclusions: The results demonstrated that the MIA sentinel node risk-prediction tool performance was robust across a wide geographical range of populations. Furthermore, the precision of the models has been substantially improved with updated CIs based on a larger population sample. This study will therefore give users greater confidence in the tool's reliability in predicting the risk of SN positivity. References [Lo2020] Lo, S. N., Ma, J., Scolyer, R. A., Haydu, L. E., Stretch, J. R., Saw, R. P. M., Nieweg, O. E., Shannon, K. F., Spillane, A. J., Ch'ng, S., Mann, G. J., Gershenwald, J. E., Thompson, J. F., Varey, A. H. R., (2020), Improved Risk Prediction Calculator for Sentinel Node Positivity in Patients With Melanoma: The Melanoma Institute Australia Nomogram, Journal of Clinical Oncology, 2719–2727, 38/24, doi: 10.1200/JCO.19.02362

Background The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. Methods EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex ® ) > 10 or change of L-Dex ® > 10 from baseline. Results Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9–62.0%], 54.1% I-IL [CI 38.0–70.1%]) and lowest at 18 months (18.8% IL [CI 5.2–32.3%], 41.4% I-IL [CI 23.5–59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6–18.7%) and L-Dex ® was 12.6 (IQR 9.0–17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. Conclusions Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study’s small sample did not have the statistical evidence to support an overall difference between the surgical groups.

Surgical wide local excision (WLE) remains the current standard of care for primary cutaneous melanoma. WLE is an elective procedure that aims to achieve locoregional disease control with minimal functional and cosmetic impairment. Despite several prospective randomised trials, the optimal extent of excision margin remains controversial, and this is reflected in the persistent lack of consensus in guidelines globally. Furthermore, there is now the added difficulty of interpreting existing trial data in the context of the evolving role of surgery in the management of melanoma, with our increased understanding of clinicopathologic and genomic prognostic markers leading to the often routine use of sentinel node biopsy (SNB) as a staging procedure, in addition to the development of adjuvant systemic therapies for high-risk disease. An ongoing trial, MelMarT-II, has been designed with the aim of achieving a definitive answer to guide this fundamental surgical decision.

Gene expression profiling (GEP) of primary cutaneous melanoma aims to offer prognostic and predictive information to guide clinical care. Despite limited evidence of clinical utility, these tests are increasingly incorporated into clinical care. A panel of melanoma experts from the Society of Surgical Oncology convened to develop recommendations regarding the use of GEP to guide management of patients with melanoma. The use of currently available GEP tests were evaluated in three clinical scenarios: (1) the utility in patient selection for sentinel lymph node biopsy; (2) the utility to guide surveillance; and (3) the utility to inform adjuvant therapy. As a basis for these recommendations, the panel performed a systematic review of the literature, including articles published from January 2012 until August 2023. After review of 137 articles, 50 met the inclusion criteria. These articles included evidence related to three available GEP tests: 31-GEP, CP-GEP, and 11-GEP. The consensus recommendations were finalized using a modified Delphi process. The panel found that current evidence often fails to account for known clinicopathologic risk factors and lacks high-level data. The panel recognizes that the study of GEP tests is still evolving. The integration of GEP into routine clinical practice for predicting sentinel lymph node status and patient prognosis in melanoma is therefore not currently recommended. At present, GEP should be considered primarily an investigational tool, ideally used in the context of clinical trials or specialized research settings.

nl/research/portal.For technical reasons the number of authors shown on this cover page is limited to 10 maximum. To the Editor,The second Multicenter Lymphadenectomy Trial (MSLT-II) is a large, international study in which patients with primary melanomas found to be sentinel node-positive were randomized to completion lymph node dissection or to