Fig. 5.

Histomorphological appearance of bone inflammation in CNO/CRMO, bacterial osteomyelitis (BOM), and Langerhans cell histiocytosis (LCH). Formalin-fixed, decalcified, and paraffin-embedded bone biopsy specimens were immune-stained with antibodies directed against CD14 (monocyte marker), NLRP3, IL-1β, and IL-10 using standard techniques (as indicated). Displayed magnification is ×100. In the top panel, HE stains are displayed. Control: trabecular bone with fatty marrow and hematopoietic tissue from a bone healthy patient undergoing osteotomy. CRMO: moderately dense infiltrate of inflammatory cells, predominantly neutrophils and monocytes, some marrow fibrosis. BOM: dense infiltrate of inflammatory cells with predominant neutrophils, cellular bone remodeling and bone necrosis. LCH: Ovoid Langerhans cells, some with linear grooves of nuclei, admixed with inflammatory cells, including a large number of eosinophils, lymphocytes, neutrophils, and plasma cells. Infiltrates of CD14-positive monocytes are a central component of inflammation in acute BOM, early phase CRMO, and LCH. Expression of the inflammasome component NLRP3 is increased in inflammatory infiltrates of BOM > CRMO > LOM, translating into IL-1 β protein expression in BOM and CRMO. As suggested by studies in ex vivo isolated monocytes, IL-10 expression in inflammatory bone lesions from CRMO patients is reduced as compared to lesions from BOM and LCH patients