Bone Tumor Reference Centre, Institute of Medical Genetics and Pathology.
Institute of Medical Genetics and Pathology.
Am J Surg Pathol. 2022 Nov 1;46(11):1577-1582. doi: 10.1097/PAS.0000000000001963. Epub 2022 Aug 30.
Brown tumors are rare and generally self-limiting mass lesions of bone occurring in the context of hyperparathyroidism. Although commonly regarded as endocrine-driven tumor-like lesions, we detected pathogenic hotspot KRAS mutations in 10/16 brown tumors (62%) with similar frequencies found in cases affecting the peripheral and axial skeleton. Pathogenic mutations in other driver genes of the RAS-MAPK pathway were not identified. Our findings suggest brown tumors to represent true neoplasms driven by the activation of the RAS-MAPK signaling pathway. The frequent regression of brown tumors after normalization of hyperparathyroidism points to a second hit mediated by endocrine stimulation to be required for tumor development. Our findings underline the pathogenic relation of brown tumors to nonossifying fibroma and giant cell granuloma of the jaws which both appear histologically similar to brown tumors and are also driven by RAS-MAPK signaling pathway activation.
棕色瘤是一种罕见的、通常具有自限性的骨内肿块病变，发生于甲状旁腺功能亢进症的背景下。尽管棕色瘤通常被认为是内分泌驱动的肿瘤样病变，但我们在 16 例棕色瘤中的 10 例（62%）中检测到了致病热点 KRAS 突变，在外周和轴性骨骼受累的病例中也发现了类似的频率。其他 RAS-MAPK 通路驱动基因的致病突变并未被发现。我们的研究结果表明，棕色瘤是由 RAS-MAPK 信号通路的激活所驱动的真正肿瘤。甲状旁腺功能亢进症得到纠正后棕色瘤的频繁消退表明，肿瘤的发展需要内分泌刺激介导的二次打击。我们的研究结果强调了棕色瘤与颌骨非骨化性纤维瘤和巨细胞肉芽肿之间的致病关系，这两种病变在组织学上与棕色瘤相似，也同样受到 RAS-MAPK 信号通路激活的驱动。
