Osteoid osteoma: the uniquely innervated bone tumor.

Osteoid osteomas are benign bone-forming tumors that despite their small size (<2.0 cm) characteristically produce severe nocturnal bone pain that is relieved by aspirin. This typical clinical presentation is virtually unique among bone tumors. Histologically, osteoid osteomas are circumscribed nodules of woven bone and osteoid with prominent osteoblastic rimming (the nidus), surrounded by thickened cortical and trabecular bone and loose fibrovascular tissue (the reactive zone). Prostaglandins mediate the pain of osteoid osteomas, but there have been few studies of their innervation. We investigated 34 osteoid osteomas using a streptavidin immunohistochemical technique and a panel of antibodies to neural and neural-associated antigens (phosphorylated neurofilament, neurofilament, and S-100 protein). Whenever possible, sections of the nidus and the reactive zone were stained. As controls, we stained other bone tumors that can be painful, including 10 osteoblastomas, 5 osteosarcomas, 6 giant cell tumors, 4 chondroblastomas, 3 aneurysmal bone cysts, and 6 cases of fibrous dysplasia. Twenty-five osteoid osteomas contained phosphorylated neurofilament-, neurofilament-, and/or S-100-positive nerve fibers in the reactive zone around the nidus and/or in the nidus. The nerve fibers were larger and more abundant in the reactive zone than in the nidus, and they were occasionally visible on hematoxylin- and eosin-stained slides on retrospective review. The smaller nerve fibers within the nidi were never identified, even after extensive review of those slides. In the nine cases in which nerve fibers were not identified, the sampled tissue consisted only of nidus. None of the control "bone tumors" contained detectable nerve fibers within their substance or in the adjacent peripheral bone. The nerve supply of osteoid osteoma seems unique among bone tumors, and it might serve as a marker in diagnostically difficult cases.