Berkin Toker

Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome

Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant IDH1 R132H protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors were associated with hypermethylation and downregulated expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation.

Applications of external fixation for management of complications associated with musculoskeletal tumors and related surgery

OBJECTIVES We evaluated the results of, and the course of treatment with, external fixation (EF) in treating complications associated with bone tumors and related surgery. METHODS Eighteen patients (9 males, 9 females; mean age 19 years; range 6 to 35 years) who were treated with EF were evaluated in three groups. Histologic diagnoses were osteosarcoma (n=3), Ewings sarcoma (n=3), hereditary multiple exostosis (n=3), chondrosarcoma (n=2), synovial sarcoma (n=2), Olliers disease, giant cell tumor of bone, desmoid fibroma, chondromyxoid fibroma, and enchondroma. Complications secondary to bone tumors (n=4) and occurring following limb salvage surgery (n=14) were treated with Ilizarov circular EF in nine patients, unilateral EF in six patients, and both in three patients. RESULTS The first group included eight patients who were treated with EF for infection and nonunion or deformity following surgery. The mean shortening was 10.6 cm, the mean lengthening was 9.7 cm, and the mean external fixator index was 48.8 days/cm. One patient developed fracture of the free vascularized fibula graft after EF removal, and amputation was required in two patients. The second group consisted of six patients who had shortening secondary to tumor surgery. The mean shortening was 7.5 cm, the mean lengthening was 6.5 cm, and the mean external fixator index was 28 days/cm. In this group, the major complications were implant failure and knee stiffness. The third group included four patients with deformity and shortening secondary to multiple exostosis (n=3) and Olliers disease. The mean shortening was 7.5 cm, the mean lengthening was 6.5 cm, and the mean external fixator index was 57.2 days/cm. One patient developed ulnar shortening of 2 cm after growth. CONCLUSION The use of EF in the management of complications associated with bone tumors and related surgery yields successful results especially in young patients.