Nevus Counts, Sun Exposure and Phenotypic Characteristics in Invasive Versus In Situ Non‐Lentigo Maligna/Non‐Acral Lentiginous Melanoma

ABSTRACT Background Evidence on phenotypic features and nevus counts for melanoma in situ (MIS) is lacking. Methods This is a retrospective study in patients diagnosed with invasive SSM or MIS, from 1999 to 2025, in melanoma referral centers in Greece and Spain. Our aim was to investigate phenotypic characteristics and nevus counts in non‐lentigo maligna/non‐acral lentiginous MIS versus invasive superficial spreading melanoma (SSM). Results In 3026 patients (2399 with invasive SSM, 627 with MIS), age did not differ between patients with invasive SSM and those with MIS. In multivariable analysis, patients who reported a history of severe sunburn were less likely to be diagnosed with invasive SSM than with MIS (odds ratio [OR]: 0.77, 95% confidence interval [95% CI]: 0.64–0.93, p = 0.007). No consistent association was observed with hair, eye color, or phototype between the two groups, both of which had predominantly dark hair and eyes. Compared with patients with few nevi, those with some or many nevi were significantly less likely to be diagnosed with invasive SSM compared to MIS (OR: 0.76, 95% CI: 0.62–0.93, and OR: 0.60, 95% CI 0.42–0.86, respectively). Conclusions The similar age at diagnosis of MIS and invasive SSM does not support an obligate progression model. The association of higher nevus counts with MIS suggests that MIS may represent a marker of proneness to melanocytic proliferation or may be preferentially diagnosed in nevus‐prone individuals undergoing closer surveillance. Further studies in phenotypically diverse populations are warranted. image