Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form.

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.

Histological and immunohistochemical study of composite neuroendocrine-exocrine carcinomas of the stomach.

Composite neuroendocrine-exocrine carcinomas (NEECs) with two distinct components of adenocarcinoma and neuroendocrine (NE) carcinoma within the same tumor are rare but may have a clue for clarifying the pathogenesis of NE tumors arising from non-endocrine organs. This study was done to characterize histological and immunohistochemical features of NEECs of the stomach comparing with pure NE tumors of the gastrointestinal (GI) tract. Microscopically, adenocarcinoma components in 6 of 8 NEECs were well differentiated and located superficially, whereas NE components were poorly differentiated and located deeply. In the remaining two cases, smaller NE components were intermingled within adenocarcinoma components. Immunohistochemically, neural cell adhesion molecule (NCAM) was positive in 5 NE components, of which 3 cases were homogeneously positive, and 2 adenocarcinoma components of 8 NEECs, while 19 of 21 pure NE tumors of GI tract were homogeneously positive for NCAM. Ghrelin-immunoreactivity was found in 4 NE components and 2 adenocarcinoma components of NEECs, although 20 pure NE tumors were positive for ghrelin. Smad4 was positive in both components of 7 NEECs. These findings suggest that composite NEECs and pure NE tumors of GI tract may have different NE properties and that most NE components of composite NEECs of the stomach may originate from an adenocarcinoma precursor cell and occasional tumors from a pluripotent cell.

[Pathology of pituitary incidentaloma].

With advance of neuroimaging technics, incidentally discovered pituitary masses (pituitary incidentalomas) are recently increased. In autopsy cases, pituitary adenomas have been discovered at the rate of 1.5-27% (mean 10%). More than 80% of these adenomas were smaller than 3 mm. Adenomas larger than 10 mm were extremely rare. Histologically autopsy adenomas were mostly PRL cell adenomas (PRLomas) and gonadotroph adenomas. Histology of autopsy PRLomas was different from that of surgically resected PRLomas. Clinically discovered pituitary incidentalomas include pituitary adenomas, Rathke's cleft cysts, and craniopharyngiomas. Most of incidental adenomas were histologically gonadotroph adenomas in our materials. Perphaps, autopsy adenomas may not grow to the clinically found incidentalomas.