Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
Department of Pathology, University Health Network, Toronto, ON, Canada.
Endocr Pathol. 2021 Mar;32(1):3-16. doi: 10.1007/s12022-021-09663-4. Epub 2021 Jan 12.
Molecular pathology has advanced our understanding of many tumors and offers opportunities to identify novel therapies. In the pituitary, the field has uncovered several genetic mutations that predispose to pituitary neuroendocrine tumor (PitNET) development, including MEN1, CDKN1B, PRKRIα, AIP, GPR101, and other more rare events; however, these genes are only rarely mutated in sporadic PitNETs. Recurrent genetic events in sporadic PitNETs include GNAS mutations in a subset of somatotroph tumors and ubiquitin-specific peptidase mutations (e.g., USP8, USP48) in some corticotroph tumors; to date, neither of these has resulted in altered management, and instead, the prognosis and management of PitNETs still rely more on cell type and subtype as well as local growth that determines surgical resectability. In contrast, craniopharyngiomas have either CTNNB1 or BRAF mutations that correlate with adamantinomatous or papillary morphology, respectively; the latter offers the opportunity for targeted therapy. DICER1 mutations are found in patients with pituitary blastoma. Epigenetic changes are implicated in the pathogenesis of the more common sporadic pituitary neoplasms including the majority of PitNETs and tumors of pituicytes.
分子病理学的发展增进了我们对许多肿瘤的了解，并为识别新的治疗方法提供了机会。在垂体中，该领域已经发现了几种导致垂体神经内分泌肿瘤（PitNET）发生的遗传突变，包括 MEN1、CDKN1B、PRKRIα、AIP、GPR101 以及其他更罕见的事件；然而，这些基因在散发的 PitNET 中很少发生突变。散发的 PitNET 中常见的遗传事件包括一些生长激素细胞瘤中的 GNAS 突变和一些促肾上腺皮质细胞瘤中的泛素特异性肽酶突变（例如 USP8、USP48）；迄今为止，这些都没有导致治疗方法的改变，相反，PitNET 的预后和治疗仍然更多地依赖于细胞类型和亚型以及决定手术可切除性的局部生长。相比之下，颅咽管瘤要么存在 CTNNB1 突变，要么存在 BRAF 突变，分别与造釉细胞瘤或乳头瘤形态相关；后者为靶向治疗提供了机会。DICER1 突变发生在垂体胚细胞瘤患者中。表观遗传变化与更常见的散发型垂体肿瘤的发病机制有关，包括大多数 PitNET 和垂体细胞肿瘤。
