Xanthogranulomatous osteomyelitis (XO) is a rare inflammatory form of osteomyelitis that can closely resemble a primary bone tumor or metastatic lesion at presentation. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and focused on pre-biopsy diagnostic clues and management decision points in published skeletal XO reports. PubMed, Embase, and Scopus were searched from January 2026 to May 2026, identifying 86 records. Eligible studies included human case reports and case series describing histologically confirmed skeletal XO or xanthogranulomatous inflammation involving bone; non-skeletal xanthogranulomatous disease, duplicate reports, review articles without extractable patient-level data, and distinct neoplastic entities were excluded. After deduplication and full-text review, 31 studies met the inclusion criteria and represented 33 patients. Data extraction was performed independently by two reviewers, and reporting quality and risk of bias were assessed using the Joanna Briggs Institute critical appraisal checklist for case reports. A neoplastic process was considered before biopsy in 29 of 31 studies (93.5%). Lytic or osteolytic destruction was described in 25/31 (80.6%), periosteal reaction in 20/31 (64.5%), a soft-tissue component in 19/31 (61.3%), and cortical breach or destruction in 16/31 (51.6%). Biopsy or histopathologic confirmation was reported in 22/31 studies (71.0%), and organism or culture data were documented in 19/31 (61.3%), supporting combined histopathologic and microbiologic evaluation. Management ranged from biopsy and debridement to reconstructive or resection procedures, depending on diagnostic uncertainty and structural risk. Overall, the literature supports XO as an important skeletal tumor mimic. An integrated clinical-radiologic-pathologic framework with early tissue confirmation and routine culture submission when tissue is obtained may help avoid inappropriate oncologic treatment and guide lesion-specific management.
Sack et al. (Sun,) studied this question.