Summary

Chronic venous leg ulcers (CVLUs) are a common dermatologic condition with significant morbidity, particularly in the elderly. While malignancy arising in the context of these ulcers is rare, the clinical and prognostic implications are profound. The most frequently associated skin cancer is squamous cell carcinoma (SCC), followed by basal cell carcinoma (BCC). These malignancies may either originate de novo or result from chronic inflammation and tissue damage in long-standing ulcers—a transformation classically referred to as Marjolin’s ulcer. The clinical differentiation between a benign chronic ulcer and one undergoing malignant transformation is often challenging due to overlapping features. Delayed diagnosis is common, often leading to advanced-stage presentations with poor outcomes, including amputation or metastatic spread. This review provides a comprehensive overview of the pathophysiologic mechanisms involved in malignant degeneration, including the role of chronic inflammation, impaired wound healing, local immunosuppression, and molecular changes such as overexpression of matrix metalloproteinases and proto-oncogenes. It also explores diagnostic strategies, with emphasis on the role of histopathological examination and clinical red flags, as well as current therapeutic options – ranging from surgical excision to adjuvant therapies in inoperable cases. Given the potentially aggressive nature of SCC arising from CVLUs, early suspicion and timely biopsy of atypical ulcers are crucial for improving patient prognosis and quality of life.