Pregnancy‐associated melanoma: New evidence and unsolved issues

Pregnancy-associated melanoma (PAM), defined as melanoma diagnosed during pregnancy or up to 1 year post-partum, represents one of the most difficult diagnostic and therapeutic challenges for both dermatologists and oncologists.1-3 PAM is considered one of the most common malignancies during pregnancy, accounting for 31% of all cancers diagnosed during gestation, albeit its real prevalence is still unknown and probably underestimated. Literature data on prognosis are still inconclusive as older studies provided evidence of a poorer prognosis of PAM compared with melanoma in non-pregnant women in terms of overall survival (OS) and disease-free survival, while a recent systematic review and meta-analysis found that pregnant women have a statistically significant higher OS rate than non-pregnant women (HR: 0.81, 95% CI: 0.69–0.95, p = 0.012, I2 = 85.4%) but no significant differences were found in terms of melanoma recurrence and mortality.2, 4 In the latest issue of JEADV, the study by Kostaki et al. provides a significant contribution to our understanding of this complex and controversial clinical entity. Analysing data from 1270 women of reproductive age diagnosed with melanoma across five European countries, the study identified PAM in 5.5% of women of reproductive age diagnosed with melanoma and provides an interesting comparison between PAM and non-pregnancy-associated melanoma (non-PAM) clinical and histopathological characteristics.1 Notably, the study reports marked regional differences in the proportion of PAM diagnosed across participating centres, ranging from 1.2% to 14.3%. This heterogeneity may reflect differences among different countries in sun exposure, potentially higher in Greece, as well as variations in public awareness regarding the need for dermatological screening during pregnancy and in the completeness of cancer registries. Kostaki et al. observed no significant difference in recurrence-free survival (RFS) between patients with PAM and those with non-PAM, with an estimated 5-year RFS rate for the entire cohort of 95%. In line with the most recent literature, these data suggest that pregnancy itself may not be an independent adverse prognostic factor in melanoma, albeit robust evidence is still missing to support this hypothesis.1, 2, 4 One of the most remarkable findings of the Kostaki study is that 57.1% of PAM and 53.7% of non-PAM developed on a pre-existing nevus, rates significantly higher than reported in the general population, where nevus-associated melanoma accounts for 29.1% of cases.1, 5 Moreover, patients with PAM were more likely to have a high-nevi count (>100 nevi) compared to the non-PAM group (p = 0.031), reinforcing the central role of constitutional melanoma risk factors even within the unique hormonal and immunologic setting of pregnancy. Since clinical and dermoscopic modification in nevi during pregnancy, due to hormonal influences and mechanical stretching, has been widely documented, these findings underscore the need for regular dermatologic evaluation and patient education regarding skin self-examination and evolving lesions during the peripartum period in order to minimize diagnostic delay.1-3 Furthermore, the study reported that non-PAM tumours exhibited significantly denser tumour-infiltrating lymphocytes (TILs) compared to PAM (32.9% vs. 24.3%, p = 0.012). Although the clinical implications remain uncertain, this finding supports the hypothesis of pregnancy-induced immune modulation, where the systemic shift towards T-helper 2 cell responses to induce immune tolerance towards the foetus may allow tumours to escape immune surveillance.1-3 The work of Kostaki et al. provides essential reassurance that pregnancy is not per se associated with a worse oncological outcome.1 However, the high incidence of PAM arising in pre-existing nevi and the potential for immune suppression during pregnancy serve as a call for heightened clinical vigilance during pregnancy and post-partum, prompting the integration of skin cancer education into routine prenatal care that may improve early detection and increase patient awareness. None. The authors have no conflicts of interest. Data sharing is not applicable to this article as no new data were created or analysed in this study.