Pregnancy-Associated Melanoma: A Molecular Reappraisal of the Hormonal Hypothesis, Illustrated by a Postpartum-Persistent Melanoma In Situ

Background and Clinical Significance: Pregnancy-associated melanoma (PAM) is clinically challenging because the physiological pigmentary and naevus changes in pregnancy can obscure early malignancy, and the long-standing assumption that the hormonal milieu of pregnancy drives melanocytic transformation continues to shape clinical expectations. We present a case of postpartum-persistent melanoma in situ and use it to anchor a molecular reappraisal of that hormonal hypothesis. Case Presentation: We describe the clinical, dermoscopic, histopathological, and immunohistochemical findings in a 32-year-old woman with a peri-umbilical naevus that changed during the third trimester and persisted twelve months postpartum, and we review the hormonal, immunological, and diagnostic literature relevant to PAM. Dermoscopy showed a multicomponent pattern with asymmetry, irregular structureless areas, peripheral pseudopods, and central regression; excisional biopsy demonstrated an atypical intraepidermal melanocytic proliferation without dermal invasion (melanoma in situ, pTis cN0 cM0, Stage 0), with Melan-A positivity and reduced p16. The reviewed evidence indicates that melanomas lack classical oestrogen/progesterone receptors and that the dominant oestrogen and α-MSH signals act through non-classical, differentiating pathways (GPER, MC1R) that are growth-suppressive rather than oncogenic, while pregnancy provides an immunologically permissive and diagnostically obscuring context. Conclusions: Pregnancy is better understood not as a hormonal driver of melanoma but as a permissive and obscuring state in which the principal preventable harm is diagnostic delay; suspicious lesions in pregnant or postpartum women warrant the same urgency as in other patients, and structured dermoscopic surveillance of at-risk women is the rational response.