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Andrea Maurichi, Francesco Barretta, Roberto Patuzzo, Rosalba Miceli, Gianfranco Gallino, Ilaria Mattavelli, Consuelo Barbieri, Andrea Leva, Martina Angi, Francesco Baldo Lanza, Giuseppe Spadola, Mara Cossa, Francesco Nesa, Umberto Cortinovis, Laura Sala, Lorenza Di Guardo, Carolina Cimminiello, Michele Del Vecchio, Barbara Valeri, and Mario Santinami

Background: Prognostic parameters in sentinel node (SN)–positive melanoma are important indicators to identify patients at high risk of recurrence who should be candidates for adjuvant therapy. We aimed to evaluate the presence of melanoma cells beyond the SN capsule—extranodal extension (ENE)—as a prognostic factor in patients with positive SNs. Methods: Data from 1,047 patients with melanoma and positive SNs treated from 2001 to 2020 at the Istituto Nazionale dei Tumori in Milano, Italy, were retrospectively investigated. Kaplan-Meier survival and crude cumulative incidence of recurrence curves were estimated. A multivariable logistic model was used to investigate the association between ENE and selected predictive factors. Cox models estimated the effect of the selected predictors on survival endpoints. Results: Median follow-up was 69 months. The 5-year overall survival rate was 62.5% and 71.7% for patients with positive SNs with and without ENE, respectively. The 5-year disease-free survival rate was 54.0% and 64.0% for patients with positive SNs with and without ENE, respectively. The multivariable logistic model showed that age, size of the main metastatic focus in the SN, and numbers of metastatic non-SNs were associated with ENE (all P<.0001). The multivariable Cox regression models showed the estimated prognostic effects of ENE associated with age, ulceration, size of the main metastatic focus in the SN, and number of metastatic non-SNs (all P<.0001) on disease-free survival and overall survival. Conclusions: ENE was a significant prognostic factor in patients with positive-SN melanoma. This parameter may be useful in clinical practice as a selection criterion for adjuvant treatment in patients with stage IIIA disease with a tumor burden <1 mm in the SN. We recommend its inclusion as an independent prognostic determinant in future updates of melanoma guidelines.

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Andrea Maurichi, Rosalba Miceli, Roberto Patuzzo, Francesco Barretta, Gianfranco Gallino, Ilaria Mattavelli, Consuelo Barbieri, Andrea Leva, Umberto Cortinovis, Elena Tolomio, Milena Sant, Gianpiero Castelli, Leonardo Zichichi, Giovanni Pellacani, Ignazio Stanganelli, Marco Simonacci, Ausilia Manganoni, Corrado Del Forno, Gioachino Caresana, Catherine Harwood, Daniele Bergamaschi, Konstantinos Lasithiotakis, Dorothy Bennett, Vittoria Espeli, Cristina Mangas, Sandra Leoni Parvex, Barbara Valeri, Mara Cossa, Marta Barisella, Alessandro Pellegrinelli, Claudia Miranda, Andrea Anichini, Roberta Mortarini, Odysseas Zoras, and Mario Santinami

Background: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. Patients and Methods: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. Results: Median follow-up was 126 months (interquartile range, 104–157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node–negative and 3 patients who were sentinel node–positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%–99.2%) and 82.2% (95% CI, 77.3%–87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. Conclusions: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.