Age-related differences in atypical Spitz tumours: characterisation and management strategies in the largest reported Italian cohort

Atypical Spitz tumours (AST) are a diagnostically challenging entity, intermediate between Spitz nevi and spitzoid melanomas. AST management does not account for their age-related peculiarities, as this aspect has not yet been thoroughly explored. Until now, no inquiry has ever surveyed AST aspects across generations, but clinicians concentrated exclusively on their topics of interest without an age-centred perspective. Besides, despite being widely executed, the prognostic utility of sentinel lymph node biopsy (SLNB) is ambiguous. The absence of a generalized consensus, that emerges as the consequence of these controversies, generates heterogeneous and uncertain care plans. We analysed the largest reported Italian cohort of ASTs with the aim to characterise their clinicopathological features across different age groups. In particular, the preliminary stratification of patients based on age aspires to refine the current practice and support guidelines implementation, thereby reducing unnecessary interventions while ensuring tailored care. Our retrospective study evaluated data on 190 ASTs diagnosed histologically by the anatomopathological centres of University Hospital of Padua (UHP) and Veneto Institute of Oncology (IOV) between 2002 and 2022. Based on age, the subjects were classified into four categories: ≤ 18, 19-25, 26-39, ≥ 40. Data collected included lesion anatomical distribution, biological characteristics (thickness, mitotic rate, ulceration, histopathological features), and management strategies. Univariate analyses were used to describe the variables and bivariate statistical analyses were employed to interpret the research evidence. The study cohort comprised 58 males (30%) and 132 females (70%), with age at diagnosis ranging from 9 to 70 years. The lower limbs were the most prevalent primary localization (52%). Tumour thickness range was 0,2 – 4,4 mm, mitotic rate encompassed none to 10 mitoses/mm2, ulceration was infrequent. Significant age-related differences were observed: the age group 0 had the highest mean tumour thickness (2,33 mm, SD. 1,35) and the highest mean mitotic rate (1,89 mitoses/mm2, SD. 2,6). Both thickness and mitotic rate decreased progressively with increasing age, with statistically significant differences among age groups. However, although ASTs in younger patients may appear histopathologically more aggressive, this has not been shown to correlate with a worse clinical outcome. 148 patients (84%) underwent treatment: ES alone (69%) or combined with SLNB (30%). Compatibly to what expected from presentation, age group 0 was subjected to the highest rate of SLNB (70,2% of the age group 0 cohort). Notably, SLNB positivity was relatively frequent in this group (41,7%), however, overall, it did not correlate significantly with age. Only one recurrence was documented in the entire cohort (group 3). Such a low rate of recurrence exemplifies how, in spite of their apparently threatening features, ASTs developing in younger age groups display an overall indolent biological course, with low risk of progression. The results underscored the variable clinicopathological characteristics of ASTs across age groups, claiming the adoption of tailored, age-dependent management strategies. Traditional prognostic indicators as tumour thickness and mitotic rate demonstrated limited predictive power for clinical outcomes, especially in younger patients. Furthermore, the lack of prognostic value of SLNB has been confirmed, suggesting SLNB selective rather than routine use, and reinforcing the importance of conservative surgical management in younger populations. The adoption of a multidisciplinary management integrating comprehensive diagnostic modalities in a III level referral centre would sustain this cumulative evidence. Prospective studies may further refine this risk stratification, and to these advancements AI is being considered for its potential role.