Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions.

[dedifferentiated liposarcoma]

To evaluate the diagnostic value of MDM 2 status in craniofacial fibro-osseous lesions , we investigated MDM 2 expression by immunohistochemistry and analyzed MDM 2 amplification by qPCR in 30 cases of ossifying fibroma (including 13 cases of the juvenile variant ) and 17 cases of fibrous dysplasia . Two cases of uncommon extragnathic psammomatoid fibrous dysplasia and a mixed control group of 15 cases of low -grade osteosarcoma and 15 cases of well-differentiated /dedifferentiated liposarcoma were included . MDM 2 amplification was found in 33 % of ossifying fibromas (peak of 69 % for the juvenile variant ) and in 12 % of fibrous dysplasia , in none of which was MDM 2 overexpressed . All control cases exhibited MDM 2 amplification and overexpression . To investigate possible polysomy of chromosome 12 , we studied RASAL 1 amplification , a gene telomeric to MDM 2 on the long arm of chromosome 12 . RASAL 1 amplification was reported in all benign fibro-osseous lesions exhibiting MDM 2 amplification but not in controls . Simultaneous amplification of these two genes was significantly higher in juvenile ossifying fibromas compared with fibrous dysplasia (P =0 .004 ), non-juvenile ossifying fibromas (P =0 .001 ), and all other benign craniofacial fibro-osseous lesions combined (P =0 .0001 ). Of the nine cases of juvenile ossifying fibroma exhibiting amplification , three were locally invasive and four were recurrent , suggesting aggressive disease . The two cases of extragnathic psammomatoid fibrous dysplasia also showed MDM 2 and RASAL 1 amplification with no MDM 2 overexpression . This large chromosome 12 rearrangement , spanning MDM 2 and RASAL 1 , is the first recurrent molecular abnormality to be reported in juvenile ossifying fibroma . It may represent both a molecular diagnostic marker and a characteristic of more aggressive forms with a higher risk of recurrence . Finally , the presence of this rearrangement in extragnathic psammomatoid fibro-osseous lesions mimicking ossifying fibromas might reflect a common molecular pathway in their pathogenesis and calls into question the classification of such lesions within fibrous dysplasia .Modern Pathology advance online publication , 13 June 2014 ; doi :10 .1038 /modpathol .2014 .80 .

Diseases
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Diseases presenting "other benign craniofacial" symptom

dedifferentiated liposarcoma

liposarcoma

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