Refractory craniofacial soft-tissue foreign-body granulomas after sequential multi-material filler injections: Imaging-based surgical management and filler-associated clinicopathologic analysis.

With the rising popularity of minimally invasive facial aesthetic procedures, injection-related complications in the cranio-maxillofacial region pose an increasing diagnostic and therapeutic challenge. We report a rare case of refractory delayed-onset inflammatory nodules in a 36-year-old woman with a self-reported allergic history following sequential injections of polyvinyl alcohol (PVA), poly-L-lactic acid (PLLA), and polycaprolactone (PCL) based biostimulatory fillers in distinct facial subunits. More than one year post-injection, the patient developed progressive erythema, induration, tenderness, and nodular swelling at multiple sites. Lesions showed poor response to intralesional corticosteroids and aspiration. High-frequency ultrasonography and magnetic resonance imaging facilitated precise lesion mapping and guided surgical excision. Site-specific histopathology revealed retained particulate material with foreign-body giant cells, granulomatous inflammation, and collagen-rich fibrosis. Exploratory transcriptomic profiling and immunofluorescence supported a shared inflammatory-fibrotic response but remained hypothesis-generating. This case underscores the clinical importance of refractory multisite foreign-body granulomas after sequential exposure to different persistent or biostimulatory injectable materials. It raises, but does not establish, the possibility of a host-related contribution and highlights the value of detailed injection history, multimodal imaging, site-specific histopathology, judicious material selection, and individualized management.