Hibernoma is a rare benign adipocytic tumor composed of a proliferation of brown and white fat cells varying in their proportions. The tumor may also contain fat cells resembling lipoblasts, which makes it difficult to distinguish it from atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDLS). Although nuclear expressions of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are widely used as immunohistochemical surrogate markers for ALT/WDLS, the utility of these proteins in distinguishing between hibernoma and ALT/WDLS still remains to be elucidated. We evaluated immunohistochemical expressions of MDM2 and CDK4 in 10 hibernomas expressing uncoupling protein-1 (UCP-1), a mitochondrial protein transporter consistently expressed in brown fat cells, and lacking MDM2 gene amplification, which was analyzed by fluorescence in situ hybridization (FISH). In contrast to the data previously obtained, nuclear expression of MDM2 was observed in 100% (10/10 cases) of the hibernomas irrespective of the proportion of brown fat cells, whereas no cases were positive for CDK4. The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specific-processing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression without MDM2 gene amplification. MDM2 expression may thus be a diagnostic pitfall for hibernoma particularly in differentiating it from ALT/WDLS.

纤维瘤是一种罕见的良性脂肪细胞性肿瘤，由棕色和白色脂肪细胞的增殖组成，它们的比例各不相同。肿瘤还可能含有类似于成脂细胞的脂肪细胞，这使其很难与非典型脂肪瘤/分化良好的脂肪肉瘤（ALT / WDLS）区分开。尽管鼠双分钟2（MDM2）和细胞周期蛋白依赖性激酶4（CDK4）的核表达被广泛用作ALT / WDLS的免疫组化替代标志物，但这些蛋白在区分冬眠瘤和ALT / WDLS中的用途仍然有待阐明。我们评估了表达脱偶联蛋白-1（UCP-1），线粒体蛋白转运蛋白在棕色脂肪细胞中持续表达且缺乏MDM2的10个冬眠瘤中MDM2和CDK4的免疫组织化学表达。基因扩增，通过荧光原位杂交（FISH）分析。与先前获得的数据相反，无论棕色脂肪细胞的比例如何，在100％（10/10例）的子宫瘤中均观察到MDM2的核表达，而CDK4则无阳性。肿瘤还显示p53（9/10例）和泛素特异性加工蛋白酶7（USP7）（10/10例）几乎同时表达，这会去泛素化并稳定MDM2，可能导致其核表达而没有MDM2基因放大。因此，MDM2表达可能是冬眠瘤的诊断陷阱，尤其是在将其与ALT / WDLS区分方面。