Suster David, Ronen Shira, Peterson Jess F, Mackinnon Alexander C, Hes Ondrej, Suster Saul, Lin Douglas I
Beth Israel Deaconess Medical Center, Department of Pathology, Harvard Medical School, Boston, MA, 02215.
Medical College of Wisconsin, Department of Pathology, Milwaukee, WI, 53226.
Hum Pathol. 2019 May;87:28-36. doi: 10.1016/j.humpath.2019.02.004. Epub 2019 Feb 28.
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.
肾细胞癌的肉瘤样变型是一种侵袭性很强的肿瘤，易于转移且治疗选择有限。肉瘤样肾细胞癌的转移有时会被误诊为各种梭形细胞肉瘤，尤其是在没有肾肿瘤病史的软组织部位。因此，在这种情况下，与某些类型软组织肉瘤相关标志物的免疫反应性可能会给诊断带来陷阱。我们评估了49例肉瘤样肾细胞癌的免疫组化和分子特征，特别强调通过免疫组化检测MDM2的表达以及通过荧光原位杂交检测MDM2扩增情况。在通过荧光原位杂交评估的49例肉瘤样肾细胞癌病例中，5例（10%）MDM2基因扩增呈阳性，5例（10%）存在12号染色体多体性。在49例病例中的30例（61%）也观察到了MDM2的免疫组化核表达；其中，19例中的15例（78%）为转移性肿瘤，30例中的15例（50%）为原发性肿瘤。免疫组化检测MDM2表达此前已在传统透明细胞肾细胞癌中报道过；然而，在肾细胞癌的肉瘤样变型中，这种现象的发生率尚未得到恰当评估。我们的研究表明，MDM2通路改变在肉瘤样肾细胞癌中相对常见，免疫组化检测MDM2核阳性以及荧光原位杂交检测MDM2扩增可能会给转移部位的去分化脂肪肉瘤诊断带来潜在陷阱。对于这些病变的诊断，建议采用免疫组化检测的综合方法。此外，识别携带MDM2拷贝数增加或基因扩增的肉瘤样肾细胞癌病例可能也具有潜在的治疗意义。
