Biomedical subjects

Eva Horvath

Publications and source records attributed to Eva Horvath.

At least 37 records · Page 2Linked to original sources

PubMed2003

Microvascular structural entropy: a novel approach to assess angiogenesis in pituitary tumors.

Entropy, a measure of the degree of disorder in a system, has recently been used in different morphologic studies to quantify regularity. Our aims were (a) to study the structural organization of the microvascular bed in prolactin (PRL)-producing adenomas and carcinomas, the most vascularized of pituitary tumors, by assessing microvascular structural entropy (MSE), and (b) to determine whether the degree of disorder of the capillary bed correlates with tumor cell proliferation as estimated by MIB-1 labeling, microvessel density (MVD), the most widely used method of quantifying blood vessel formation, and various clinicopathologic parameters (gender, age, tumor size and invasiveness). The morphometric study demonstrated statistically significant differences in MIB-1 labeling, MVD, and MSE between PRL-producing adenomas and carcinomas. Unlike MIB-1 labeling index (PRL-producing adenomas 1.5 +/- 0.27; carcinomas 15.0 +/- 4.04) and MVD (PRL-producing adenomas 2.7 +/- 0.34; carcinomas 4.2 +/- 0.72), the MSE values were significantly higher in adenomas (171.5 +/- 25.37) than in carcinomas (67.9 +/- 17.45). These results indicate that PRL-producing carcinomas have a less chaotic distribution of vessels than benign adenomas. In contrast to a lack of correlation between microvessel density and other morphometric parameters, a strong negative correlation was found between MSE and MIB-1 labeling index (r = 0.511, p = 0.003). It thus appears that regular, less chaotic microvascular geometry contributes to increased proliferative activity in PRL cell tumors. Analysis of MSE may provide an independent parameter of tumor behavior, and contributes to a better understanding of the role of microvasculature in pituitary tumor progression.

Adenoma↗

PubMed2003

Pathology of pituitary tumors.

Pituitary adenomas are benign neoplasms originating in adenohypophysial cells. They represent the most common neoplasm of the sellar region, comprising approximately 15% of all primary intracranial tumors. Depending on the studies of unselected adult autopsy material, their frequency as an incidental finding varies between 5% and 20%. The first part of this article summarizes the immunohistochemistry of nontumorous human adenohypophysis. In the second part, the classification of pituitary tumors is discussed, followed by the immunohistochemical and electron microscopic findings of pituitary adenomas and pituitary carcinomas.

Adenoma↗

PubMed2003

Effect of gamma knife radiosurgery on a pituitary gonadotroph adenoma: a histologic, immunohistochemical and electron microscopic study.

The morphologic findings in a pituitary macroadenoma removed from a 65-year old man by the transsphenoidal approach 9 months after gamma knife surgery are reported. The tumor was immunoreactive for FSH beta and showed ultrastractural features consistent with an oncocytic gonadotroph adenoma. Accumulation of connective tissue separating small groups of adenoma cells was evident. Several dilated vessels and numerous vascular endothelial growth factor immunopositive adenoma cell were noted. By electron microscopy the endothelial linings frequently showed discontinuities with platelet accumulation attached to the gaps. Several vessels were severely injured showing necrosis of endothelial cells. It can be concluded that gamma knife surgery caused severe alterations in pituitary adenoma microcirculation indicating that vascular injury plays a crucial role in tumor shrinkage.

Adenoma↗

PubMed2003

Immunohistochemical localization of amylin in human pancreas, thyroid, pituitary and their tumors.

The aim of the present study was to investigate immunohistochemically expression of amylin, a 37 amino acid peptide, cosecreted with insulin by beta cells in pancreatic islets in 12 non-tumorous pancreatic tissues, 22 pancreatic islet tumors, 14 non-tumorous thyroids, 14 medullary carcinomas of the thyroid, 10 non-tumorous pituitaries and 50 pituitary adenomas including 10 amyloid-forming prolactin-cell adenomas using the streptavidin-biotin-peroxidase complex method. Amylin was expressed in non-tumorous pancreatic islets but not in non-tumorous thyroids and pituitaries. Since amylin plays an important role in amyloid formation in pancreatic islets, those tumor types were selected to study which may produce amyloid. Amylin was widely expressed in one insulin producing beta cell tumor. Few tumor cells were immunopositive in 8 islet-cell tumors and in 5 medullary thyroid carcinomas. Immunostaining was not found in pituitary adenomas, including those which produced amyloid. It can be concluded that amylin is not a satisfactory immunohistochemical marker to identify pancreatic islet tumors, medullary thyroid carcinomas and pituitary adenomas.

Amyloid↗

PubMed2003

Silent corticotroph carcinoma of the adenohypophysis: a report of five cases.

We report five silent corticotroph carcinomas of the pituitary gland. They represent 0.05% of adenohypophyseal tumors surgically treated at Mayo Clinic during a 20-year period and about 5% of all reported pituitary carcinomas. The patients (three females and two males), ranging in age from 26 to 58 years (mean 39 years, median 35 years) presented with symptoms of mass effect; none had Cushing's disease. All tumors were initially invasive macroadenomas, recurred locally, and metastasized, three outside the central nervous system. The follow-up period ranged from 2 to 23 years (mean 10.6 years). All patients died, four of disseminated tumor and one of myocardial infarction. Histologically, three of the primary lesions were indistinguishable from an ordinary benign adenoma. Two were initially diagnosed as atypical adenomas as they featured nuclear pleomorphism, prominent nucleoli, mitotic activity, high MIB-1 labeling indices, and p53 overexpression. For the purpose of comparison, 17 silent corticotroph adenomas were also investigated. In addition, the clinicopathologic features of the silent carcinomas were compared with those of a meta-analysis of published Cushing's disease-associated pituitary carcinomas. The silent adrenocorticotropin carcinomas showed a propensity for extraneural dissemination and an outcome similar to those of the Cushing's disease-associated carcinomas. The two patients with initial atypical tumors died with metastases outside the central nervous system at 2 and 4 years, whereas the three patients with tumors lacking atypia died 16, 18, and 23 years after initial sellar surgery.

Adult↗

PubMed2003

Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma.

Cushing's disease is caused by functional corticotroph adenomas of the pituitary, mostly noninvasive microadenomas. Classic Crooke's cells are nonneoplastic corticotrophs with cytoplasmic accumulation of cytokeratin filaments in response to glucocorticoid excess. Corticotroph adenomas exhibiting Crooke's change are rare and incompletely understood. We intend to define more clearly the clinicopathological features of Crooke's cell adenomas (CCA). Thirty-six CCAs were retrieved from the files of Mayo Clinic and from our (B.W.S., K.K.) consultation files. The number of informative cases varied for different criteria. Clinical follow-up was obtained in 31 cases. The 27 females and 9 males were 18 to 81 years of age (mean 46 years). At presentation, Cushing's disease was evident in 22/34 (65%); 81% were macroadenomas and 72% were invasive. All were initially treated by transsphenoidal resection. Twenty-five patients were followed for more than 1 year (mean 6.7 years). Of these, 15 (60%) developed recurrent tumor, and 6 (24%) had multiple recurrences. Lastly, 3 of these 25 patients (12%) died of tumor: 1 after multiple local recurrences and 2 from pituitary carcinoma. Compared with typical corticotroph adenomas, CCAs are aggressive. Most are functional adenomas occurring in middle-aged women and are invasive macroadenomas prone to recurrence. Morbidity and mortality rates are substantial. CCAs represent a distinct entity that should be separated from corticotroph adenomas without Crooke's hyaline change.

Adenoma↗

PubMed2003

Juxtaposition of an ectopic corticotroph adenoma of the sphenoid sinus with orthotopic intrasellar corticotroph hyperplasia in a patient with Cushing disease. Case report.

Ectopic pituitary adenomas (EPAs) are rare and their association with orthotopic corticotroph hyperplasia has not been published. The case of a 30-year-old woman with clinical and biochemical evidence of Cushing disease (CD) is reported. A magnetic resonance image obtained preoperatively revealed asymmetrical inhomogeneity of the pituitary gland, which was suggestive of localized adenoma. It also showed what was thought to be a small sphenoid polyp. Postoperatively the latter lesion was found to be an ectopic corticotroph adenoma. The pituitary gland, which was free from any tumor, exhibited diffuse unilateral corticotroph hyperplasia. Clinical, radiological, laboratory, and histopathological findings are presented. A review of the literature and a discussion of possible causes of this unique association between the ectopic corticotroph adenoma and the pituitary hyperplasia are provided.

ACTH Syndrome, Ectopic↗

PubMed2003

Gonadotropic pituitary carcinoma: HER-2/neu expression and gene amplification. Report of two cases.

The authors report on two gonadotropic carcinomas of the adenohypophysis that occurred in a55-year-old man (Case 1) and a 53-year-old woman (Case 2), with signs of mass effect and amenorrhea, respectively. Both lesions were macroadenomas. The tumor in Case 1 metastasized to dura mater, skull, nasal sinus, and larynx 2 years after patient presentation, whereas that in Case 2 spread to vertebral bodies and ribs after a 19-year latency. Histologically, the primary, recurrent, and metastatic lesions in Case 1 featured brisk mitotic activity and high MIB-1 levels as well as p53 labeling indices. Immunoreactivity for HER-2/neu was assessable only in rare neoplastic cells of the second recurrence and in 80% of cells of the dural metastasis. Low-level HER-2/neu gene amplification was evident in the recurrent tumors and metastasis. The sellar and metastatic tumors in Case 2 resembled benign gonadotropic adenoma with oncocytic change; p53 accumulation, HER-2/neu overexpression, and HER-2/neu gene amplification were not present. The results indicate that low-level amplification of the HER-2/neu gene might be associated with pituitary carcinomas in which more aggressive behavior is seen. Further studies are needed to determine whether HER-2/neu plays a role in the pathogenesis of pituitary carcinoma.

Brain Neoplasms↗

PubMed2002

Neural transformation in a pituitary corticotroph adenoma.

A pituitary mass was removed by the transsphenoidal approach from a 63-year-old man with the clinical history and laboratory findings characteristic of Cushing's disease with partial hypopituitarism. Histological, immunohistochemical, ultrastructural and immunoelectron microscopic investigation demonstrated a periodic acid-Schiff-positive, adrenocorticotropic hormone (ACTH)-immunoreactive, pituitary corticotroph adenoma with the formation of neural tissue resembling neuropil within the tumor. The neural elements showed immunopositivity for neurofilament protein and ACTH, but were immunonegative for other adenohypophysial hormones and for corticotropin-releasing hormone. Although the molecular mechanism accounting for neural transformation in this corticotroph adenoma remained obscure, based on the clinical, histological and morphological findings it appears that formation of neural tissue most likely indicate a favorable prognosis.

Adenoma, Chromophobe↗

PubMed2002

'Spindle cell oncocytoma' of the adenohypophysis: a tumor of folliculostellate cells?

We describe five primary tumors of the adenohypophysis featuring mitochondrion-rich spindle cells. The patient ages ranged from 53 to 71 years (mean 61.6 years); two were female. All presented with panhypopituitarism. Two also had visual field defect. On neuroimaging all tumors showed suprasellar extension and were indistinguishable from pituitary adenoma. None showed imaging or operative evidence of dural involvement. All were gross totally removed: four by transsphenoidal surgery and one by frontal craniotomy. Follow-up ranged from 2 to 68 months (mean 35.4 months). No recurrences were noted. The clinical workup was noncontributory in all but two patients: one (case no. 4) with an oncocytic thyroid adenoma and another (case no. 5) with squamous carcinoma of both the uterine cervix and of vocal cord. Histologically, the five tumors were composed mainly of fascicles of spindle cells with eosinophilic, granular cytoplasm. Mitoses were rare and necrosis was absent. Neoplastic cells were immunoreactive for vimentin, epithelial membrane antigen, S-100 protein, and galectin-3. Stains for pituitary hormones, synaptophysin, chromogranin, glial fibrillary acidic protein, cytokeratin CAM5.2, smooth muscle actin, CD34, and CD68 were negative. No thyroglobulin immunoreactivity was noted in the tumor of case no. 4. Ultrastructurally, the neoplastic cells contained numerous mitochondria with lamellar cristae. The neoplastic cells were linked by intermediate junctions and desmosomes. No secretory granules were noted. The histologic, immunohistochemical, and fine structural features of these tumors were unlike those of pituitary adenoma or any other primary sellar tumor. A derivation from adenohypophyseal folliculostellate cells is suggested.

Adenoma, Oxyphilic↗

PubMed2002

Topoisomerase IIalpha expression in pituitary adenomas and carcinomas: relationship to tumor behavior.

DNA topoisomerase IIalpha (Topo IIalpha) is a molecular and immunohistochemical marker that indicates proliferation rate and is the target for several antineoplastic agents. The present immunohistochemical study of a large series of surgically removed pituitary tumors was designed to assess the prognostic significance of Topo IIalpha expression relative to patient age, gender, tumor type and size, invasiveness, metastasis, MIB-1-labeling index and angiogenesis. Changes of Topo IIalpha expression in the tumors treated with bromocriptine and octreotide, a long-acting somatostatin analogue were also investigated. Topo IIalpha immunopositivity was detected only in the nuclei of tumor cells. Gonadotroph adenomas, null cell adenomas, and ACTH-producing adenomas had the lowest Topo IIalpha indices, whereas primary pituitary carcinomas and silent type 3 adenomas presented the highest counts. The statistical study demonstrated no significant correlation between Topo IIalpha expression, patient gender, and vascularity. In contrast, significant negative correlation was found between Topo IIalpha expression and patient age. Topo IIalpha expression was significantly higher in invasive than noninvasive tumors. A tendency to have higher counts was also observed in microadenomas compared with in macroadenomas. Although Topo IIalpha and MIB-1 indices were similar in most tumor types, no significant correlation between Topo IIalpha and MIB-1-labeling indices (r =.16, P =.09) was found. Only non-functioning adenomas showed positive correlation (r =.41, P =.006) between both proliferation markers. Our results demonstrated a significant decrease in Topo IIalpha index in octreotide-treated, GH-producing adenomas, compared with untreated tumors, but no significant changes were observed in bromocriptine-treated, PRL-producing adenomas. The present study showed no significant advantage of Topo IIalpha over MIB-1 as a prognostic marker; however, Topo IIalpha may provide crucial information regarding selection of adenohypophyseal tumors responsive to antineoplastic therapy, such as invasive pituitary adenomas and pituitary carcinomas, which exhibit a high Topo IIalpha index.

Adenoma↗

PubMed2002

Immunocytochemical localization of mast cells in lymphocytic hypophysitis.

We studied 15 transsphenoidally resected pituitary tissues diagnosed by histologic examination as chronic lymphocytic hypophysitis. Six autopsy-obtained pituitaries of patients who died of nonendocrine diseases also were studied. Tryptase immunohistochemical analysis, which specifically identifies mast cells, demonstrated numerous, randomly distributed multifunctional cells throughout the inflammatory reaction. Several mast cells were located in the vicinity of capillaries; several others were distributed far from the blood vessels. Occasional mast cells also were noted in the nonpathologic anterior and posterior pituitary lobes. Morphometric analysis confirmed that in lymphocytic hypophysitis, the number of mast cells per volume of tissue was significantly increased compared with that of nonpathologic anterior and posterior pituitary lobes. To elucidate the possible role of mast cells in chronic lymphocytic hypophysitis, microvessel densities were assessed quantitatively using immunohistochemical analysis for CD34, a sensitive marker of endothelial cells. The strong positive correlation between numeric density of mast cells and microvessel density per volume of pituitary tissue suggests that mast cell-derived products may influence capillary permeability and angiogenesis, thereby facilitating the access of inflammatory cells to adenohypophysial cells.

Adult↗

PubMed2002

Prolactin-producing pituitary adenoma associated with prolactin cell hyperplasia.

A 24-yr-old woman with amenorrhea, galactorrhea, hyperprolactinemia, and sellar mass underwent transsphenoidal surgery. Histologic, immunohistochemical, and electron microscopic investigation revealed a well-differentiated, sparsely granulated prolactin (PRL) cell adenoma of the pituitary showing conclusive PRL immunoreactivity. In the nontumorous adenohypophysis PRL cell hyperplasia was noted. Marked differences were evident between the neoplastic and hyperplastic areas. The tumor consisted of sparsely granulated PRL cells immunoreactive only for PRL. As demonstrated by immunoelectron microscopy, the hyperplastic area comprised monohormonal sparsely granulated PRL cells as well as bihormonal mammosomatotrophs immunoreactive for both PRL and growth hormone. The MIB-1 index was higher whereas microvessel density was lower in the adenoma as compared with the hyperplastic area. In addition, the nontumorous area showed lymphocytic infiltration whereas inflammatory reaction was not seen in the adenoma. This case represents a rare association of a PRL cell adenoma and PRL cell hyperplasia. The fact that these two lesions were contiguous in the surgically removed material raises the possibility that hyperplasia can precede and transform into adenoma.

Adult↗

PubMed2002

Growth factors and cytokines in paragangliomas and pheochromocytomas, with special reference to sustentacular cells.

The aim of this study was to localize various growth factors and cytokines in paragangliomas and pheochromocytomas in order to understand their possible autocrine or paracrine functions, and to compare sustentacular cells of the adrenal medulla with pituitary stellate cells. Thirteen resected tumors, 11 paragangliomas and 2 pheochromocytomas of the adrenal medulla, were studied. In addition, five surgically removed nontumorous adrenals and five nontumorous pituitaries were studied. Varying numbers of sustentacular cells were immunopositive for S-100 protein and in most instances for glial fibrillary acidic protein. Insulin-like growth factor-1 (IGF-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 were localized to both cell types in all cases, whereas epidermal growth factor (EGF) immunopositivity was noted in only three. In all tumors, leukemia inhibitory factor (LIF) was restricted to chief cells and EGF receptor to sustentacular cells. Nontumorous chief cells and sustentacular cells of adrenal medulla exhibited immunoreactivities similar to those of paragangliomas and pheochromocytomas. Secretory adenohypophysial cells displayed various immunoreactivities for all growth factors, receptors, and cytokines studied. Pituitary stellate cells were immunopositive for EGF, EGF receptor, IGF-1, LIF, and TNF-alpha. In conclusion, paragangliomas and pheochromocytomas are immunoreactive for a wide spectrum of growth factors and cytokines. Immunocytochemistry demonstrated similarities between sustentacular cells and stellate cells of the pituitary in addition to their similar morphology. The significance of these observations regarding paracrine activities of chief and sustentacular cells remains to be determined.

Adrenal Gland Neoplasms↗

PubMed2002

An immunohistochemical survey of nine cases of medullary carcinoma of thyroid including reactivity for Cox-1 and Cox-2 enzymes.

There has been much recent investigation of the cyclooxygenase (Cox) enzymes in tumor biology, but, to our knowledge, no study has yet been published describing Cox activity in medullary carcinoma of the thyroid (MTC). Nine cases of MTC from the past 10 yr were retrieved from our hospital archives. Slides cut from formalin-fixed paraffin-embedded tumor tissue from these cases were assessed for the activities of Cox-1 and Cox-2 enzymes by immunohistochemistry as well as by a battery of immunohistochemical stains for intermediate filaments, peptide hormone, and proliferation and promoter antigens. The staining reactions were semiquantitatively assessed and scored for comparison with each other as well as with each patient s clinical presentation and course. Staining for Cox-1 and Cox-2 enzymes was present only in tumorous tissue, not in nontumorous thyroid tissue or C-cells. Cox-2 staining was not consistently increased over Cox-1 staining; however, Cox-2 staining bore statistically significant correlations with the expression of low molecular weight keratin, thyroid-transforming factor-1, topoisomerase, and MIB1. Hyperplastic C-cells from patients with diverse physiologic conditions and from three patients with C-cell hyperplasia accompanying medullary carcinoma or multiple endocrine neoplasia type IIa showed no reactivity for the Cox antibodies. It appears that Cox enzyme immunoreactivity is present only in the neoplastic C-cells of medullary carcinoma, but with variable expression. A practical application of the preceding finding might involve the use of Cox staining to distinguish invasive medullary carcinoma cells from hyperplastic C-cells.

Adult↗

PubMed2002

Corticotroph carcinoma of the pituitary: a clinicopathological study. Report of four cases.

To understand the relationship between pituitary adenoma and carcinoma, four adrenocorticotropic hormone-producing pituitary adenomas and corresponding metastatic carcinomas were studied. All were functional macroadenomas (three cases of Nelson syndrome and one of Cushing disease) that initially invaded the sella turcica and occurred in women ranging in age from 17 to 66 years (mean 45 years). Metastases (two craniospinal and two systemic) occurred after latency periods of 6 to 13 years. Histological specimens were immunostained for pituitary hormones, Ki-67 antigen (MIB-1), p53 and p27 proteins, D-type cyclins, and glucocorticoid receptor messenger (m)RNA. The DNA content of the specimens was assessed using Feulgen stain. Reactivities were quantified by digital image analysis. Primary/recurrent lesions and metastatic tumors differed according to their respective mean mitotic indices (1.2/10 hpf compared with 4.3/10 hpf), MIB-1 labeling (1.7% compared with 8%), p53 staining (37.3% compared with 49.9%), and p27 labeling (48% compared with 25%). Cyclin D, immunoreactivity provided no prognostically significant information. Glucocorticoid receptor mRNA was detected in all cases. Results of a ploidy analysis were variable and nonprognostic. In keeping with the 2000 World Health Organization classification of endocrine neoplasms, our findings support the concept that primary tumors that exhibit mitotic activity, an increased (> 3%) MIB-1 labeling index, and/or p53 immunoreactivity should be termed "atypical adenomas" to denote their aggressive potential and the possibility of future malignant transformation.

Adenoma↗

PubMed2000

Octreotide Effect on Growth Hormone and Somatostatin Subtype 2 Receptor mRNAs of the Human Pituitary Somatotroph Adenomas.

Octreotide, a somatostatin analog used to treat acromegalic patients harboring a pituitary tumor, acts via somatostatin subtype 2 receptor (SSTR2) and causes significant decrease of circulating GH levels and sometimes mild to moderate tumor shrinkage. To further elucidate the mechanism of octreotide action, we studied GH and SSTR2 mRNAs by in situ hybridization in densely and sparsely granulated somatotroph adenomas removed by surgery from 14 treated and 14 untreated patients. Only in densely granulated adenomas were the GH and SSTR2 mRNA signals mildly decreased relative to untreated matched adenomas. The decrease of GH mRNA in densely granulated somatotroph adenomas suggests that they may have a more favorable response to octreotide therapy than sparsely granulated tumors.

Journal Article↗

PubMed1999

Xanthomatous Hypophysitis: A Novel Entity of Obscure Etiology.

We report a case of xanthomatous hypophysitis, a recently described entity of obscure etiology affecting the pituitary gland, in a 43-yr-old woman, Histologically it is characterized by infiltration of the anterior pituitary by foamy histiocytes which are strongly immunoreactive for CD68 (histiocytic marker) and are immunonegative for 5100 and CD 1 a. Electron microscopy revealed histiocytes with abundant cytopasmic lipid droplets and membrane bound vacuoles. Fragments of intact anterior pituitary with preserved vascw lar and reticulin networks are seen. Xanthomatous hypophysitis resembles neoplasm on clinical and radiologic grounds.

Journal Article↗