Isocitrate Dehydrogenase (IDH1/IDH2) Mutation Types and Frequency in Periosteal Cartilaginous Tumors
Jodi M Carter, Jesse S Voss, Benjamin R Kipp, Doris E Wenger, Carrie Y Inwards. Mayo Clinic, Rochester, MN
Background: Primary cartilaginous tumors arising on the surface of bone include benign periosteal chondromas and their malignant counterparts, periosteal chondrosarcomas. Recently, somatic mutations in isocitrate dehydrogenase (IDH1/IDH2), encoding an enzyme in the tricarboxylic acid cycle, have been reported in cartilaginous tumors. However, the rarity of periosteal cartilaginous tumors, particularly periosteal chondrosarcomas, has limited the evaluation of IDH mutational status in these tumors. We evaluated IDH mutational types and frequency in a series of periosteal cartilaginous tumors.
Design: Cases of periosteal chondromas (N=9) and periosteal chondrosarcomas (N=6) were retrieved from our institutional archives. Histologic slides and radiologic images (when available) or reports were reviewed. DNA was extracted from paraffin-embedded tumor tissue and IDH1 (codon 132) and IDH2 (codon 172) were evaluated by PCR and pyrosequencing and/or direct sequencing.
Results: Periosteal chondromas presented in 5 males and 4 females (median age 29 years, range 4-51 years) as small masses (mean 2.1 ± 0.9 cm). Among them, seven (78%) had heterozygous mutations in IDH1 (phalanges N=3, humerus N=2, calcaneus and fibula, N=1); including the R132C (71%) and R132H (29%) mutation. Mutations in IDH2 were not detected. Periosteal chondromas with wildtype IDH (N=2) occurred in the humerus and tibia. Periosteal chondrosarcomas presented in 3 males and 3 females (median age 43 years, range 15-72 years) as large masses (mean 5.8 ± 2.3cm). Among them, two (33%) had heterozygous mutations in IDH, including IDH1 R132C (spine), and IDH2 R172G (tibia). Periosteal chondrosarcomas with wildtype IDH (67%) occurred in the humerus (2), femur and pubis. There was no association between IDH mutational status and patient age, tumor size or location.
Conclusions: In our series, IDH1 mutations occurred in 78% of periosteal chondromas, comparable to the published literature. However, while IDH1 R132C was the most frequent mutation type in periosteal chondromas, R132H mutations, not previously reported in this tumor subset, comprised the second largest group. In our series of periosteal chondrosarcomas, the IDH mutation rate was 33%, which differs from the 100% mutation rate reported in the few cases in the literature. Also, we report the first case of periosteal chondrosarcoma harboring an IDH2 (R172G) mutation. Our data comprise the largest series of IDH mutational data in perisoteal chondrosarcomas reported to date and contribute to the emerging spectrum of IDH mutations in cartilaginous tumors.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 1, Tuesday Afternoon