Squamous Cell Carcinoma Arising from Chronic Osteomyelitis: A Single-Center Case Series of Six Patients

Chronic osteomyelitis (COM) is a persistent bone infection. Long-standing COM may lead to malignant transformation, most commonly squamous cell carcinoma (SCC). However, due to its rarity and nonspecific clinical presentation, early diagnosis remains challenging. This study aimed to characterize the clinical features, microbiological profiles, management strategies, and outcomes of SCC arising from COM.

We retrospectively reviewed six consecutive patients diagnosed with SCC secondary to COM at Shanghai Sixth People's Hospital from January 2021 up to May 2026. Diagnosis was confirmed histopathologically. Demographic data, duration and etiology of osteomyelitis, clinical manifestations, microbiological findings, imaging features, treatment approaches, and follow-up outcomes were systematically analyzed.

Six patients (three men and three women) with a median age of 57.5 years (interquartile range, 48.2-61.5) were included. The median duration of osteomyelitis before malignant transformation was 12 years. Lesions were predominantly located in the lower extremities (5/6, 83.3%), and one case involved the thumb (1/6, 16.7%). The most common symptoms included purulent discharge, pain and ulceration. Microbiological analysis revealed a predominance of Gram-negative organisms, including Klebsiella, Escherichia coli, and Pseudomonas aeruginosa, differing from the traditionally reported predominance of Staphylococcus aureus. Imaging revealed aggressive local bone destruction but lacked specific features suggestive of malignancy. Amputation was performed in 5 of 6 patients (83.3%), and one patient developed lymphatic metastasis and received systemic chemotherapy. At a median follow-up of 7.5 months, all patients were alive, with no evidence of local recurrence.

SCC should be suspected in patients with long-standing COM with worsening ulceration, increased discharge, or mass formation. Early biopsy is essential for a definitive diagnosis. The observed predominance of Gram-negative pathogens within this cohort generates a hypothesis regarding potential links between microbial characteristics and malignant transformation. Radical surgery, including amputation, achieves effective local disease control. Timely identification of malignant change may offer opportunities for limb-sparing treatment and improved functional outcomes.