Lentigo maligna (LM) is a common subtype of melanoma in situ arising on chronically sun-damaged (CSD) skin. Diagnosis and management rely on morphological assessment, including clinical examination, dermoscopy ,reflectance confocal microscopy (RCM), and histopathology. These methods can be challenging because LM often has subtle features and may be difficult to distinguish from adjacent CSD skin. Molecular studies may provide complementary information to improve diagnostic precision and management. However, research on LM is limited, and no studies have examined its proteomic profile or compared it with surrounding skin to identify altered pathways.
Methods:
A scarless biopsy technique was used in which superficial layers of the stratum corneum were sequentially removed using adhesive discs, followed by protein extraction and quantification with liquid chromatography–mass spectrometry (LC-MS/MS). The study included 42 adults with clinically and histologically confirmed LM attending the Dermatology Clinic at Westmead Hospital between 2021 and 2024. RCM was performed to map lesions and guide sampling from three regions: LM centre, LM edge, and adjacent normal skin. Participants then underwent surgical excision with histological confirmation of residual LM , margins and normal skin . Differential abundance analysis compared protein expression between regions. Ingenuity Pathway Analysis (IPA) identified disrupted biological pathways.
Results:
No statistically significant differentially abundant proteins were identified between groups. However, pathway analysis comparing LM centre with normal skin suggested activation of carcinogenesis-related pathways involving metabolism, epithelial integrity, immune and inflammatory signalling, stress responses, and regulation of tumour cell migration. In contrast, LM edge compared with surrounding skin showed enrichment of pathways related to apoptosis and immune cell responses.
Conclusion:
This discovery proteomic study provides preliminary evidence of molecular differences between LM, lesion edge, and surrounding skin. Although no individual proteins reached significance, pathway-level findings suggest biologically relevant alterations that may improve understanding of LM pathogenesis and help future research.