Clinicopathological Features of Growth Hormone-producing Pituitary Adenomas: Difference among Various Types Defined by C
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Clinicopathological Features of Growth Hormone-producing Pituitary Adenomas: Difference among Various Types Defined by Cytokeratin Distribution Pattern Including a Transitional Form Abdulkader Obari & Toshiaki Sano & Kenichi Ohyama & Eiji Kudo & Zhi Rong Qian & Akiko Yoneda & Nasim Rayhan & Muhammad Mustafizur Rahman & Shozo Yamada
Published online: 16 July 2008 # Humana Press Inc. 2008
Abstract 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, β-TSH, αsubunit, E-cadherin, and β-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. Keywords pituitary adenoma . growth hormone . fibrous body . cytokeratin . immunohistochemistry
Introduction A. Obari : T. Sano (*) : K. Ohyama : E. Kudo : Z. R. Qian : A. Yoneda : N. Rayhan : M. Mustafizur Rahman : S. Yamada Department of Human Pathology, Institute of Health Bioscience, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan e-mail: [email protected] E. Kudo : S. Yamada Division of Hypothalamus and Hypophyseal Surgery, Toranomon Hospital, Tokyo, Japan
Pituitary tumors are mostly adenomas, with growth hormone (GH)-producing type (GH cell adenoma) accounting for 10–15% [1, 2]. GH cell adenomas that cause acromegaly comprise several tumor types [2, 3], but “pure” GH cell adenomas, which are composed of almost exclusively GH cells, have been ultrastructurally classified into two distinct subtypes: densely granulated GH cell ade
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