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

• Published in: Modern pathology Vol. 25; no. 10; pp. 1384 - 1396
• Main Authors: Kashima, Takeshi, Halai, Dina, Ye, Hongtao, Hing, Sandra Nalini, Delaney, David, Pollock, Robin, O'Donnell, Paul, Tirabosco, Roberto, Flanagan, Adrienne Margaret
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-10-2012; Elsevier Limited
• Subjects: 631/208/737/1505; 692/699/67; 692/700/139/1512; Adult; Aged; Centromere - genetics; Chromosomes; DNA, Satellite - genetics; Female; Gene Amplification; Gene Dosage; Genetic Markers - genetics; Histopathology; Humans; In Situ Hybridization, Fluorescence - methods; Laboratory Medicine; Lipoma - diagnosis; Lipoma - genetics; Lipoma - metabolism; Liposarcoma; Liposarcoma - diagnosis; Liposarcoma - genetics; Liposarcoma - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; original-article; Orthopedics; Pathology; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Soft Tissue Neoplasms - diagnosis; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - metabolism; Tumors; United Kingdom > UK; dedifferentiated liposarcoma; well-differentiated liposarcoma; FISH; MDM2; alpha satellite sequence 12 (alphoid 12); atypical lipomatous tumor; molecular diagnosis
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2012.90

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 >10 cm, two dedifferentiated liposarcoma presented
de novo
at <10 cm, and ∼50% of lipomas measured >10 cm. Spindle cell lipomas, lipoblastomas, hibernomas and pleomorphic liposarcomas did not reveal
MDM2
amplification. Of 201 non-lipomatous 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.