Departments of *Immunology, Genetics and Pathology §Medical Sciences ∥Surgical Sciences, Uppsala University †Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden ‡Department of Pathology, Oslo University Hospital, Oslo, Norway ¶Department of Pathology, Odense University Hospital #Department of Clinical Research, University of Southern Denmark, Odense, Denmark **Faculty of Medicine Lyon-Est ††Centre de Pathologie et de Biologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, University of Lyon, Lyon, France.
Am J Surg Pathol. 2017 Sep;41(9):1238-1246. doi: 10.1097/PAS.0000000000000908.
Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.
基于形态学和免疫组织化学的鉴别诊断，在鞍区临床无功能的垂体神经内分泌肿瘤（NET）/垂体腺瘤与原发性或继发性非垂体来源的 NET 之间可能具有一定难度。在 NET 中广泛表达的标志物 5-羟色胺（serotonin），尚未在垂体 NET 中进行系统评估。尽管在相当比例的胰腺 NET 中已报道存在 ATRX 或 DAXX 的突变，但 ATRX 和 DAXX 的突变状态及其在垂体 NET 中的可能致病作用尚不清楚。在面对一例具有侵袭性的鞍区 5-羟色胺和促肾上腺皮质激素免疫反应性 NET 的疑难诊断病例时，我们在 246 例不同类型的垂体内分泌肿瘤患者和 2 例促皮质素细胞瘤中，探索了 5-羟色胺、ATRX 和 DAXX 的免疫组织化学表达。没有垂体肿瘤表达 5-羟色胺，提示鞍区具有 5-羟色胺免疫反应性的肿瘤代表原发性或继发性非垂体来源的 NET。在垂体肿瘤中 ATRX 和 DAXX 的正常表达表明，ATRX 和 DAXX 不会在仍然局限于鞍区和鞍旁区域的垂体内分泌肿瘤的发病机制中发挥作用。在鞍区 NET 中缺乏 ATRX 或 DAXX 提示为非垂体 NET，可能来源于胰腺。然而，在检查的 2 例促皮质素细胞瘤中，由于 ATRX 基因突变，其中 1 例存在 ATRX 免疫标记阴性。需要对更大队列的垂体癌进行进一步研究，以阐明 ATRX 突变是否可能导致部分垂体 NET 具有转移潜能。
