Abstract
BACKGROUND: In the American Joint Committee on Cancer (AJCC) classification, acral lentiginous melanoma (ALM) histotype ALM is not included as an independent prognostic factor; in small series its negative prognostic impact on disease-free survival (DFS) and overall survival (OS) has been linked to the greater Breslow thickness (BT). PATIENTS AND METHODS: The study was carried out at four referral melanoma centers (three Italian and one Polish). Clinical consecutive patients with stage I-II melanoma, who were diagnosed, treated, and followed up between January 1998 and March 2018 in annotated specific databases were included. RESULTS: Overall, 6734 were evaluable, 4349 with superficial spreading melanoma (SSM), 2132 with nodular melanoma (NM), and 253 with ALM. At univariable analysis, a statistically significant worse DFS [hazard ratio (HR) 2.72, 95% confidence interval (CI) 2.24-3.30; P < 0.001] and OS (HR 2.67, 95% CI 2.15-3.32; P < 0.001) were found in patients with ALM compared with SSM. Similarly, the NM histotype was associated with a worse prognosis compared with the SSM histotype (DFS: HR 2.29, 95% CI 2.08-2.52; P < 0.001 and OS: HR 2.21, 95% CI 1.99-2.46; P < 0.001). At multivariable analysis, after adjusting for age, sex, BT, ulceration, and the sentinel lymph node status, a statistically significant worse DFS [adjusted HR (aHR; ALM versus SSM) 1.25, 95% CI 1.02-1.52; P = 0.028] was confirmed for patients with ALM. For patients with NM, instead, no impact of histology was found in terms of DFS [aHR (NM versus SSM) 1.04, 95% CI 0.93-1.15; P = 0.513] and OS [aHR (NM versus SSM) 0.96, 95% CI 0.86-1.08; P = 0.548]. CONCLUSIONS: ALM is associated with a worse long-term DFS. Our results could have important clinical implications for patients' stratification in future clinical trials and the incorporation of ALM histotype in the new AJCC classification as an independent prognostic factor.