Introduction
Marjolin's ulcer is a rare but highly aggressive cutaneous malignancy that develops in chronic wounds and scars, most commonly as squamous cell carcinoma. Although chronic inflammation has long been implicated in its pathogenesis, the biological mechanisms linking traumatic injury to malignant transformation remain incompletely understood. This review aims to integrate current evidence from trauma biology, wound healing, microbiology, immunology, and cancer biology to propose a comprehensive mechanistic framework describing the progression from traumatic wounds to Marjolin's ulcer.
Method
Relevant literature addressing traumatic wound healing, chronic wound microbiology, biofilm biology, inflammatory signaling, molecular carcinogenesis, and Marjolin's ulcer pathogenesis was critically reviewed and synthesized to develop an integrated conceptual model.
Discussion
We propose the Microbial–Inflammatory–Carcinogenic Continuum, a systems-level framework describing malignant transformation as a sequential and interconnected process. Following traumatic injury, disruption of the skin barrier promotes microbial dysbiosis and biofilm formation, leading to persistent activation of innate immunity and chronic inflammatory signaling. Sustained production of pro-inflammatory cytokines, reactive oxygen and nitrogen species, and matrix metalloproteinases promotes oxidative stress, extracellular matrix degradation, genomic instability, epigenetic reprogramming, impaired immune surveillance, pathological angiogenesis, epithelial–mesenchymal transition, and cancer stem cell niche formation. These mechanisms interact through multiple positive feedback loops, progressively converting a chronic non-healing wound into a tumor-promoting microenvironment. This model also reconciles existing mechanistic theories by integrating microbial, inflammatory, immunological, and genetic pathways into a unified pathogenic framework.
Conclusion
Marjolin's ulcer should be regarded as the end result of a dynamic microbial–inflammatory–carcinogenic continuum rather than the consequence of a single pathogenic event. This integrated perspective provides a biological basis for improved risk stratification, biomarker discovery, early diagnosis, and the development of targeted preventive and therapeutic strategies for patients with chronic traumatic wounds.