Challenging dedifferentiated liposarcoma identified by MDM2-amplification, a report of two cases

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• 作者：Suvi Lokka (1)
  Andreas H Scheel (1) (2)
  Sebastian Dango (3) (4)
  Katja Schmitz (2)
  Rudolf Hesterberg (3)
  Josef R眉schoff (1)
  Hans-Ulrich Schildhaus (2)
  
  1. Institute of Pathology Nordhessen ; Germaniastr. 7 ; 34119 ; Kassel ; Germany
  2. Department of Pathology ; University Medical Centre G枚ttingen ; Robert-Koch-Str. 38 ; 37077 ; G枚ttingen ; Germany
  3. Department of Surgery ; Rotes Kreuz Krankenhaus ; Hansteinstrasse 29 ; 34121 ; Kassel ; Germany
  4. Department of General ; Visceral ; and Paediatric Surgery ; University Medical Centre G枚ttingen ; Robert-Koch-Str. 38 ; 37077 ; G枚ttingen ; Germany
  
• 关键词：Dedifferentiated Liposarcoma ; Liposarcoma with osteoblastic component ; MDM2 ; Fluorescence in situ hybridisation
• 刊名：BMC Clinical Pathology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：5,369 KB
• 参考文献：1. Dei Tos, AP (2000) Liposarcoma: New entities and evolving concepts. Ann Diagn Pathol 4: pp. 252-266 CrossRef
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  2. Mentzel, T, Schneider-Stock, R Lipogen differenzierte Tumoren. In: Kl枚ppel, G, Kreipe, HH, Remmele, W eds. (2008) Pathologie (Kopf-Hals-Region, Weichgewebstumoren, Haut). Springer, Berlin - Heidelberg, pp. 401-403
  3. Nascimento, AG (2001) Dedifferentiated liposarcoma. Semin Diagn Pathol 18: pp. 263-266
  4. Crago, AM, Singer, S (2011) Clinical and molecular approaches to well-differentiated and dedifferentiated liposarcoma. Curr Opin Oncol 23: pp. 373-378 CrossRef
  5. Weaver, J, Downs-Kelly, E, Goldblum, JR, Turner, S, Kulkarni, S, Tubbs, RR, Rubin, BP, Skacel, M (2008) Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol 21: pp. 943-949 CrossRef
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  8. Kashima, T, Halai, D, Ye, H, Hing, SN, Delaney, D, Pollock, R, O'Donnell, P, Tirabosco, R, Flanagan, AM (2012) Sensitivity of MDM2 amplification and unexpected multiple faint alphoid 12 (alpha 12 satellite sequences) signals in atypical lipomatous tumour. Mod Pathol 25: pp. 1384-1396 CrossRef
  9. Kimura, H, Dobashi, Y, Nojima, T, Nakamura, H, Yamamoto, N, Tsuchiya, H, Ikeda, H, Sawada-Kitamura, S, Oyama, T, Ooi, A (2013) Utility of fluorescence in situ hybridization to detect MDM2 amplification in liposarcomas and their morphological mimics. Int J Clin Exp Pathol 6: pp. 1306-16
  10. Gardner, JM, Dandekar, M, Thomas, D, Goldblum, JR, Weiss, SW, Billings, SD, Lucas, DR, McHugh, JB, Patel, RM (2012) Cutaneous and subcutaneous pleomorphic liposarcoma: a clinicopathologic study of 29 cases with evaluation of MDM2 gene amplification in 26. Am J Surg Pathol 36: pp. 1047-51 CrossRef
  11. Le Guellec, S, Chibon, F, Ouali, M, Perot, G, Decouvelaere, AV, Robin, YM, Larousserie, F, Terrier, P, Coindre, JM, Neuville, A (2014) Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?. Am J Surg Pathol 38: pp. 293-304 CrossRef
  12. Yoshida, A, Ushiku, T, Motoi, T, Shibata, T, Beppu, Y, Fukayama, M, Tsuda, H (2010) Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics. Mod Pathol 23: pp. 1279-1288 CrossRef
  13. Thomas, DM, O'Sullivan, B, Gronchi, A (2009) Current concepts and future perspectives in retroperitoneal soft-tissue sarcoma management. Expert Rev Anticancer Ther 9: pp. 1145-57 CrossRef
  14. Vassilev, LT, Vu, BT, Graves, B, Carvajal, D, Podlaski, F, Filipovic, Z, Kong, N, Kammlott, U, Lukacs, C, Klein, C, Fotouhi, N, Liu, EA (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303: pp. 844-848 CrossRef
  15. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1472-6890/14/36/prepub
  
• 刊物主题：Pathology; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1472-6890

文摘

Background Liposarcoma is the most frequent soft tissue sarcoma. Well differentiated liposarcoma may progress into dedifferentiated liposarcoma with pleomorphic histology. A minority additionally features myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of the Mouse double minute 2 homolog (MDM2) locus is characteristic for well differentiated and dedifferentiated liposarcomas. Detection of MDM2 amplification may supplement histopathology and aid to distinguish liposarcoma from other soft tissue neoplasia. Case presentation Here we present two cases of dedifferentiated liposarcoma with challenging presentation. Case 1 features a myogenic component. As the tumour infiltrated the abdominal muscles and showed immunohistochemical expression of myogenic proteins, rhabdomyosarcoma had to be ruled out. Case 2 has an osteosarcomatous component resembling extraosseous osteosarcoma. The MDM2 status was determined in both cases and helped making the correct diagnosis. Overexpression of MDM2 and co-overexpression of Cyclin-dependent kinase 4 is demonstrated by immunohistochemistry. The underlying MDM2 amplification is shown by fluorescence in situ hybridisation. Since low grade osteosarcoma may also harbour MDM2 amplification it is emphasised that the amplification has to be present in the lipomatous parts of the tumour to distinguish liposarcoma from extraosseous osteosarcoma. Conclusions The two cases exemplify challenges in the diagnoses of dedifferentiated liposarcoma. Liposarcoma often has pleomorphic histology and additionally may feature heterologous components that mimic other soft tissue neoplasms. Amplification of MDM2 is characteristic for well differentiated and dedifferentiated liposarcomas. Determination of the MDM2 status by in situ hybridisation may assist histopathology and help to rule out differential diagnoses.