The sarcomatoid variant of renal cell carcinoma is a highly aggressive tumor with propensity for metastasis and limited therapeutic options. Metastases of sarcomatoid renal cell carcinoma can sometimes be mistaken for a variety of spindle cell sarcomas, particularly at soft tissue sites in the absence of a history of a kidney tumor. Immunoreactivity for markers associated with certain types of soft tissue sarcomas can, therefore, pose a pitfall for diagnosis under such circumstances. We evaluated the immunohistochemical and molecular features of 49 cases of sarcomatoid renal cell carcinoma with special emphasis on the expression of MDM2 by immunohistochemistry and MDM2 amplification by fluorescence in situ hybridization. Of the 49 sarcomatoid renal cell carcinoma cases evaluated by fluorescence in situ hybridization, 5 (10%) were positive for MDM2 gene amplification and 5 (10%) contained polysomy 12. Immunohistochemical nuclear expression for MDM2 was also observed in 30/49 (61%) cases; of these, 15/19 (78%) were metastatic and 15/30 (50%) were primary. MDM2 expression by immunohistochemistry has been previously reported in conventional clear cell renal cell carcinoma; however, occurrence of this phenomenon has not yet been properly assessed in the sarcomatoid variant of renal cell carcinoma. Our study demonstrates that alterations of the MDM2 pathway are relatively frequent in sarcomatoid renal cell carcinoma, and nuclear positivity for MDM2 by immunohistochemistry, as well as MDM2 amplification by fluorescence in situ hybridization may pose a potential pitfall for diagnosis with dedifferentiated liposarcoma at metastatic sites. A panel approach to immunohistochemical testing is recommended for the diagnosis of these lesions. Also, identification of cases of sarcomatoid renal cell carcinomas harboring MDM2 copy number gain or gene amplification may also have potential therapeutic implications.
Keywords: FISH; MDM2 Amplification; RCC; Renal; Sarcomatoid.
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