R132C IDH1 Mutations Are Found in Spindle Cell Hemangiomas and Not in Other Vascular Tumors or Malformations
Kyle C Kurek, Twinkal C Pansuriya, Maayke AJH van Ruler, Brendy van den Akker, Valerie Luks, Sofie LJ Verbeke, Harry P Kozakewich, Raf Sciot, Dina Lev, Alexander J Lazar, Christopher DM Fletcher, Judith VMG Bovee. Boston Children's Hospital, Boston, MA; Leiden University Medical Center, Leiden, Netherlands; University of Leuven, Leuven, Belgium; MD Anderson Cancer Center, Houston, TX; Brigham and Women's Hospital, Boston, MA
Background: Spindle cell hemangioma is a rare benign vascular tumor of the dermis and subcutaneous tissue, presenting mainly in children and young adults. The lesions can be multifocal, and are overrepresented among patients with the rare Maffucci syndrome in which patients also have multiple enchondromas. Somatic mosaic R132C hotspot mutations were recently identified in Maffucci syndrome.
Design: We evaluated the presence of IDH mutations in solitary and multiple spindle cell hemangiomas occurring in patients without multiple enchondromas. In addition we tested a range of other vascular lesions that enter the differential diagnosis of spindle cell hemangioma, in order to evaluate the specificity of IDH1 mutations and to identify a possible role in the differential diagnosis of vascular lesions.
Results: In total 18 of 28 (64%) spindle cell hemangiomas demonstrated the R132C IDH1 mutation using the hydrolysis probes assay, confirmed by Sanger sequencing. Of the 10 negative cases, 2 demonstrated a mutation in IDH2 (R172T and R172M) by Sanger sequencing. None of 154 other vascular malformations and tumors examined contained an IDH1 R132C mutation. R132H IDH1 mutations were absent in all cases. All 16 spindle cell hemangiomas examined were negative for the expression of HIF-1α by immunohistochemistry.
Conclusions: In conclusion, 20 of 28 (71%) spindle cell hemangiomas harbored mutations in the IDH1 or -2 genes, 18 of which (90%) occurred specifically at R132C in IDH1. Since mutations were absent in 154 other vascular malformations and tumors, the mutation seems to be highly specific for spindle cell hemangioma within the differential diagnosis with other vascular lesions. The mutation does not induce expression of HIF-1α in spindle cell hemangioma, and therefore the exact mechanism by which mutations in IDH lead to vascular tumorigenesis remains to be established.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 8:15 AM
Proffered Papers: Section G, Tuesday Morning