Clinicopathological features of growth hormone-producing pituitary adenomas: Difference among various types defined by cytokeratin distribution pattern including a transitional form
Clinicopathological features of growth hormone-producing pituitary adenomas: Difference among various types defined by cytokeratin distribution pattern including a transitional form
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DOI：
10.1007/s12022-008-9029-z
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Yamada, Shozo
中科院分区：
文献类型：
--
作者：
Obari, Abdulkader;Sano, Toshiaki;Yamada, Shozo
几乎只产生生长激素（GH）的垂体腺瘤在超微结构上分为两种不同的类型：密集颗粒状生长激素（DG）腺瘤和稀疏颗粒状（SG）腺瘤。纤维体（FB），细胞角蛋白（CK）细丝的胞浆内球状聚集，是SG腺瘤的标志。在光镜下，FB可以通过CK免疫组织化学鉴定为点图案的免疫反应，而非FB的细胞的核周图案。然而，已经注意到许多腺瘤包含两种模式的混合群体。为了阐明混合人群腺瘤（“中间型”腺瘤）的临床病理学特征，并确认严格定义的DG型和SG型腺瘤之间的临床病理学差异，我们对104例GH细胞腺瘤进行了这项研究。具有分离的“中间型”腺瘤（26例），我们发现典型DG型之间有显著差异（47例）和SG型腺瘤（31例）; SG型腺瘤发病年龄较年轻（44 vs. 50），大腺瘤发生率较高（86% vs. 58%），侵袭性（65% vs. 38%），Knosp分类中的晚期（3或4级）（50% vs. 24%），GH、β-TSH、α-亚单位、E-钙粘蛋白和β-连环蛋白的免疫反应较弱。“中间型”腺瘤的临床病理特征与DG型腺瘤相同。这些发现证实SG型腺瘤是GH细胞腺瘤的一个独特部分，具有特殊的性质和生物学行为，并表明中间表型腺瘤属于DG型腺瘤。SG型腺瘤的特殊性质和生物学行为可能出现在大多数肿瘤细胞具有充分发育的纤维体之后。
Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.