title: Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form.
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, 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.
authors.affiliation: Department of Human Pathology, Institute of Health Bioscience, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, Japan.
authors.forename: Abdulkader
authors.initials: A
authors.lastname: Obari
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohyama
authors.forename: Eiji
authors.initials: E
authors.lastname: Kudo
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoneda
authors.forename: Nasim
authors.initials: N
authors.lastname: Rayhan
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mustafizur Rahman
authors.forename: Shozo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000172:Acromegaly / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002452:Cell Count; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism* / Q000473:pathology*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013972:Thyrotropin / Q000378:metabolism; D016707:Tissue Fixation; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051176:beta Catenin; D019382:Human Growth Hormone; D007633:Keratins; D013972:Thyrotropin