In the case of sporadic tumors, the majority do not have recurrent genetic alterations and the disease is thought to be attributed to epigenetic alterations that may be associated with environmental challenges or stress.58 A few specific tumor types have a clear pattern of genetic changes that have predictive value: the densely granulated somatotroph tumors have activating GNAS mutations that provide the mechanism for their somatostatin-responsiveness, and densely granulated corticotroph tumor have been reported to harbor mutations of USP8, USP48 or BRAF. Here, USP48 is linked to neoplasm.