Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, M5G 2M9, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5G 2M9, Canada.
Mod Pathol. 2018 Jun;31(6):900-909. doi: 10.1038/s41379-018-0016-8. Epub 2018 Feb 12.
Recent studies have reported the prevalence of pituitary tumors to be ~1/1000 population. Many are prolactin-producing tumors that are managed medically, however, the epidemiology of surgically resected pituitary adenohypophysial neuroendocrine tumors has not been reported in a large series with detailed characterization. We reviewed 1055 adenohypophysial tumors from 1169 transsphenoidal resections from the pathology files of University Health Network, Toronto, 2001-2016. Tumors were characterized by immunohistochemical localization of transcription factors (Pit-1, ERα, SF-1, Tpit), hormones (adrenocorticotropin, growth hormone, prolactin, β-thyrotropin, β-folliculotropin, β-luteotropin, α-subunit), and other biomarkers (keratins, Ki67, p27, FGFR4). Electron microscopy was used only for unusual lesions. In this cohort, 51.3% of patients were female; the average age was 51 years. Gonadotroph tumors represented 42.5%. Pit-1-lineage-tumors represented 29.9%; these were subclassified as growth-hormone-predominant (somatotroph/mammosomatotroph/mixed; 53%), prolactin-predominant (lactotroph/acidophil-stem-cell; 28%), thyrotrophs (2%), plurihormonal (14%), and not-otherwise-specified (3%). Corticotroph tumors represented 17.1%. Only 4.5% were null cell tumors and 0.5% were unusual plurihormonal tumors. In 5.5% the tumor was not characterized for technical reasons (sample size, fixation, necrosis or other artifact). All corticotroph and plurihormonal tumors were positive for keratins; others tumors showed variable negativity with highest rates in gonadotroph (37.1%) and null cell tumors (28.2%). Tumors with a Ki67 ≥ 3% comprised 60% of this cohort. Global loss of p27 was most frequent in corticotroph neoplasms, specifically those associated with elevated glucocorticoid levels. Corticotroph and lactotroph tumors were more common among females; gonadotroph tumors were more common among males. Younger patients had mainly corticotroph and Pit-1-lineage neoplasms, whereas older patients harbored mainly gonadotroph tumors. This represents one of the largest surgical series of morphologically characterized pituitary tumors reported to date and the first to include the routine use of transcription factors for tumor classification. The data provide the basis for clinicopathologic correlations that are helpful for prognostic and predictive patient management.
最近的研究报告称，垂体肿瘤的患病率约为每 1000 人中有 1 例。许多是催乳素分泌性肿瘤，通过药物治疗进行管理，然而，大型系列研究中并未报道过经过详细特征描述的手术切除垂体腺神经内分泌肿瘤的流行病学情况。我们对来自多伦多大学健康网络病理学档案的 1169 例经蝶窦切除术的 1055 例腺垂体肿瘤进行了回顾性研究，时间范围为 2001 年至 2016 年。肿瘤通过转录因子（Pit-1、ERα、SF-1、Tpit）、激素（促肾上腺皮质激素、生长激素、催乳素、β-促甲状腺激素、β-卵泡刺激素、β-黄体生成素、α-亚单位）和其他生物标志物（角蛋白、Ki67、p27、FGFR4）的免疫组织化学定位进行特征描述。仅对异常病变使用电子显微镜。在该队列中，51.3%的患者为女性；平均年龄为 51 岁。促性腺激素肿瘤占 42.5%。Pit-1 谱系肿瘤占 29.9%；这些肿瘤被细分为生长激素优势型（生长激素/催乳素/混合；53%）、催乳素优势型（催乳素/嗜酸细胞干细胞；28%）、促甲状腺激素瘤（2%）、多激素型（14%）和未分类（3%）。促肾上腺皮质激素瘤占 17.1%。仅有 4.5%为无细胞肿瘤，0.5%为罕见的多激素肿瘤。由于技术原因（样本量、固定、坏死或其他伪影），有 5.5%的肿瘤未进行特征描述。所有促肾上腺皮质激素和多激素肿瘤均为角蛋白阳性；其他肿瘤的角蛋白表达存在不同程度的缺失，在促性腺激素（37.1%）和无细胞肿瘤（28.2%）中缺失率最高。Ki67≥3%的肿瘤占本队列的 60%。皮质醇瘤中 p27 的全局缺失最为常见，特别是那些与皮质醇水平升高相关的肿瘤。促肾上腺皮质激素和催乳素肿瘤在女性中更为常见；促性腺激素肿瘤在男性中更为常见。年轻患者主要患有促肾上腺皮质激素和 Pit-1 谱系肿瘤，而年长患者则主要患有促性腺激素肿瘤。这是迄今为止报道的最大的形态学特征描述的垂体肿瘤手术系列之一，也是第一个常规使用转录因子进行肿瘤分类的系列。该数据为有助于预测患者预后和管理的临床病理相关性研究提供了基础。
