Clinical characteristics, treatment, and prognosis of squamous cell carcinoma arising from extremity chronic osteomyelitis: a synthesis analysis of one hundred and seventy six reported cases

Abstract

Purpose: Squamous cell carcinoma (SCC) arising from extremity chronic osteomyelitis (COM) has not been well-understood due to its low prevalence. This study aimed to synthesize the cases recently published to clarify their clinical characteristics, treatment, and prognosis. Methods: PubMed, Embase, and Cochrane Library databases were searched for English literature reporting cases diagnosed of SCC originating from extremity COM between January 1, 1990, and September 30, 2019. The National Institutes of Health (NIH) assessment tool was used to evaluate the quality of reports included, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to summarize the quality of available evidence. The data synthesized for analysis were clinical features, treatment strategy, and incidences of local recurrence, metastasis, all-cause, and SCC-related deaths. In addition, potential factors that might have influenced treatment efficacy and prognosis of SCC were also investigated. Results: Included for this analysis were 60 studies of 176 patients (a male-to-female ratio of 6.7). COM mostly occurred following trauma (73%), the tibia was the most frequent site (61%), and a sinus tract was the most common symptom (61%). The mean duration from COM to SCC was 27 years. Positive rate of pathogen culture was 90%, with 73% being polymicrobial. Limb amputation was performed in 80.5% of the patients. Incidences of local recurrence, metastasis after treatment, all-cause, and SCC-related mortalities were 16.7%, 12%, 31.1%, and 12.6%, respectively. Patients with local lymphadenopathy at diagnosis had significantly higher risks of local recurrence (P = 0.01), SCC-related (P = 0.02), and all-cause deaths (P = 0.01) than those without. Patients with moderately-to-poorly differentiated SCC types had significantly higher risks of local recurrence (P = 0.01) and all-cause death (P = 0.02) than those with a well-differentiated type. Conclusions: SCC arising from extremity COM favoured males and the tibia. Although limb amputation was the mainstay of treatment, the overall incidences of local recurrence, metastasis, and SCC-related death exceeded 10%. Patients with local lymphadenopathy at diagnosis of SCC and those with moderately-to-poorly differentiated SCC types should be followed up closely. Trial registration: CRD42020154221.