Sensitivity of MDM2 amplification and unexpected multiple faint alphoid 12 (alpha 12 satellite sequences) signals in atypical lipomatous tumor

Abstract

This study assessed whether analysis of MDM2 copy number by fluorescence in situ hybridization (FISH) would help distinguish lipomas from atypical lipomatous tumors, otherwise referred to as well-differentiated liposarcomas, using a commercially available MDM2 FISH kit. 227 lipomatous and 201 non-lipomatous tumors were analyzed to assess its sensitivity and specificity. Of 178 mature lipomatous tumors, 86 were classified histologically as lipoma and 92 as atypical lipomatous tumor. Two of the lipomas harboring MDM2 amplification were reclassified as atypical lipomatous tumors. Overall, 13 atypical lipomatous tumors did not reveal MDM2 or CDK4 amplification, although this was reduced to 12 following analysis of multiple slides. Three of these cases revealed very occasional tumor cells harboring high-level MDM2 amplification, two had a dedifferentiated component, and MDM2 amplification was detected when one tumor recurred. The remaining six cases exhibited reactive/inflammatory features and were reclassified as lipomas. The findings indicate that MDM2 amplification is 93.5% sensitive for diagnosing atypical lipomatous tumor. A total of 2 of the 20 dedifferentiated liposarcomas failed to reveal MDM2 amplification. All atypical lipomatous tumors measured 410 cm, two dedifferentiated liposarcoma presented de novo at o10 cm, and B50% of lipomas measured 410 cm. Spindle cell lipomas, lipoblastomas, hibernomas and pleomorphic liposarcomas did not reveal MDM2 amplification. Of 201 nonlipomatous tumors, eight revealed MDM2 amplification or multiple faint alphoid 12 signals and were reclassified as dedifferentiated liposarcoma. Multiple faint alphoid 12 signals were observed in nine tumors from seven patients, an observation not previously reported on paraffin sections: these included four atypical lipomatous tumors, and three dedifferentiated liposarcomas, one previously diagnosed as a myxofibrosarcoma, all of which also revealed amplification of CDK4, although two lacked MDM2 amplification. MDM2 FISH test is a useful adjunct to histology for distinguishing lipoma from atypical lipomatous tumor. The limitations of molecular genetic tests must be known before introducing them into a clinical service.

FluorescenceIn SituHybridization forMDM2Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center

“…These results are broadly similar to the concordance rates of 85–100% in other published data [37–39, 41, 42], although those studies used cases in which firm histologic diagnoses had been made and did not consider “equivocal” diagnoses. Our series includes a large number of equivocal and uncertain histologic diagnoses, and it should be emphasized that the large majority of specimens analyzed by FISH in this study were those in which there was a level of diagnostic uncertainty; hence unequivocal cases of lipomas or DDL with adjacent WDL component were not tested.…”

Malignant solitary fibrous tumor with high-grade nuclear atypia: An alternate entity for the undetermined tumor group

“…Thus, we propose that even if known patterns of NAB2-STAT6 fusion gene and nuclear STAT6-immunostaining are not detected, fusion genepositive SFT cannot be ruled out. In addition, a past exploration of sarcoma with MDM2 amplification other than dedifferentiated liposarcoma qualified two high-grade tumors in our study to be classified in malignant solitary fibrous tumors [13]. GRIA2 was also a newly established diagnostic clue of solitary fibrous tumor [14], but it could not clearly differentiate SFTs and SFTs with high-grade nuclear atypia in this study.…”

GNAS mutations are not detected in parosteal and low-grade central osteosarcomas

“…24 The fluorescent in situ hybridization probe for MDM2 on chromosome 12 with its respective chromosome enumeration probe was purchased from Zytovision (Zytovision GmbH, Bremerhaven, Germany), Zytolight SPEC MDM2/CEN12 (centromere 12; Z-2013) Dual Colour Probes. Non-informative cases were excluded from the analysis.…”