Biomedical subjects

Eva Horvath

Publications and source records attributed to Eva Horvath.

48 records · Page 3Linked to original sources

PubMed1999

Plurihormonal Bronchial Carcinoid Associated with Ectopic Cushing's Syndrome.

A 31-year-old woman presented with progressive weight gain, facial acne, round facies, hirsutism, and secondary amenorrhea. Her plasma cortisol, urinary free cortisol, and plasma ACTH were elevated. CT scan of abdomen revealed bilateral diffuse adrenal enlargement. MRI of pituitary failed to identify a lesion. CT scan of chest revealed an 8 mm nodule in the lower lobe of the left lung. The diagnosis of ectopic Cushing's syndrome was made. The lung tumor was surgically removed. The tumor measured up to 1.5 cm in diameter. By light microscopy, a tumor with characteristic features of bronchial carcinoid was noted. Immunostains were positive for neuron-specific enolase, synaptophysin, chromogranin, low-molecular-weight keratin, ACTH, beta endorphin, corticotropin-releasing hormone, bombesin, alpha subunit, and somatostatin. Electron microscopy revealed an endocrine neoplasm. The secretory granules displayed great variation subdividing the endocrine neoplasm. The secretory granules displayed great variation subdividing the cell population into an undetermined number of phenotypes. In situ hybridization demonstrated positivity for pro-opiomelanocortin mRNA in the tumor cells. Postoperatively, plasma cortisol had fallen. The patient remained symptom-free one year later. The case presented here was regarded as a plurihormonal bronchial carcinoid associated with ectopic Cushing's syndrome. This unique plurihormonal bronchial carcinoid tumor produced three hormones, ACTH, CRH, and bombesin, that may have contributed to the patient's ectopic Cushing's syndrome.

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PubMed1997

Pituitary Changes in Ataxia-Telangiectasia Syndrome: An Immunocytochemical, In Situ Hybridization, and DNA Cytometric Study of Three Cases.

Ataxia-telangiectasia (AT) syndrome (cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, susceptibility to infections, and neoplasia) is associated with cyto- and nucleomegaly in several organ systems. Our aim was to determine (1) whether such cellular abnormalities in the pituitary selectively involve specific cell types, and (2) the proliferation and DNA ploidy status of such cells. Three AT autopsy pituitaries were studied by histology, immunohistochemistry (pituitary hormones, MIB-1, p53 protein), in situ hybridization (pituitary hormones), and Feulgen stain image analysis for ploidy. Results indicated that, in adenohypophyses the scattered pleomorphic, bizarre nuclei were mainly those of somatotrophs and corticotrophs, growth hormone (GH), or adrenocorticotropic hormone (ACm) immunoreactive and expressing the GH or ACTH gene, respectively. Cyto- and nucleomegaly were less frequent in other secretory cells but were also noted in pituicytes of the posterior lobe. Affected cells were immunonegative for MIB-1 and for p53 protein. Image morphometric DNA analysis showed the bizarre cells to be aneuploid with complex histogram patterns, including many nuclei with DNA contents >8 n. No adenomas were found. We conclude that in AT adenohypophyseal cells with cyto- and nucleomegaly, as well as pleomorphism, synthesize and store adenohypophyseal hormones, mainly GH or ACTH. They and affected pituicytes are nonproliferative and are aneuploid.

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PubMed1997

Cushing's Syndrome from an Ectopic Pituitary Adenoma with Peliosis: A Histological, Immunohistochemical, and Ultrastructural Study and Review of the Literature.

Ectopic pituitary adenoma (EPA) is rare and, to the authors' knowledge, its association with peliosis has not yet been described. The case of a 38-yr-old woman with clinical and biochemical evidence of Cushing's syndrome is reported. Magnetic resonance imaging (MRI) disclosed a normal pituitary and a separate mass in the sphenoid sinus. The surgically removed portion of the sellar pituitary contained no adenoma. There was only Crooke's hyaline change in the corticotrophs, indicating exposure to glucocorticoid excess. By histology, the mass in the sphenoid sinus was a congested, chromophobic, partly basophilic, periodic acid-Schiff (PAS)-positive pituitary adenoma composed of pleomorphic, adrenocorticotropic hormone (ACTH)-positive, corticotrophs. There was focal immunopositivity for MIB-1 and proliferating cell nuclear antigen (PCNA). Electron microscopy confirmed the diagnosis of corticotroph adenoma. A striking finding, consistent with the diagnosis of peliosis, was the presence of multiple large blood-filled spaces lacking an endothelial lining. The capillaries were dilated, but often appeared empty and the fenestrated endothelium exhibited discontinuities. The cause of peliosis is obscure. It may be that the venous outflow was impaired in this case leading to capillary dilation, congestion, hyperpermeability, rupture, and accumulation of blood in extravascular spaces.

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PubMed1996

Pituitary Corticotroph Adenoma in a Woman with Long-Standing Addison's Disease: A Histologic, immunocytochemical, Electron Microscopic, and In Situ Hybridization Study.

A 64-year-old woman with long-standing Addison's disease owing to destructive immune adrenalitis presented with hyperpigmentation and progressively increasing blood adrenocorticotrophic hormone (ACTH) levels. Magnetic resonance imaging demonstrated a pituitary microadenoma, which was removed by transsphenoidal surgery and investigated by histology, immunocytochemistry, transmission electron microscopy, and in situ hybridization (ISH). The morphologic studies revealed a basophilic, periodic acid-Schift (PAS)-positive pituitary adenoma immunoreactive for ACTH and B-endorphin and in several cells for a-subunit. By transmission electron microscopy, the tumor was a densely granulated corticotroph adenoma, which, by ISH, expressed pro-opiomelanocortin (POMC) mRNA. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis was an intriguing finding. Corticotroph adenomas in patients with long-standing Addison's disease were very rarely examined by morphology. Our report includes a detailed morphologic analysis and is the first demonstration of POMC mRNA in the tumor cells using ISH. The question of whether the adenoma was related to increased secretory activity secondary to protracted hypocorticism or developed independently unrelated to deranged endocrine homeostasis remains unresolved. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis favors the interpretation that hypothalamic stimulation played no major role in adenoma formation in our case.

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PubMed1996

The Anterior Pituitary in Hemochromatosis.

Pituitary changes in the case of a 69-year-old man with hemochromatosis are reported. The patient died of complications of hepatocellular carcinoma. The pituitary removed at autopsy was studied by histology, histochemistry, immunocytochemistry, electron microscopy, and X-ray diffraction. Preferential localization of iron deposits was demonstrated within gonadotrophs, which, at the ultrastructural level, displayed selective, severe cellular injury. X-ray diffraction revealed the deposition of iron-accumulated lysosomes. Iron storage also was noted in stellate cells. We consider selective injury of pituitary gonadotrophs to be the basis of hypogonadism in iron-overloaded states.

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PubMed1995

Incidence, Pathology, and Recurrence of Pituitary Adenomas: Study of 647 Unselected Surgical Cases.

The incidence of various types of unselected pituitary adenomas based on correlation of pathologic and clinical data was assessed. We investigated 647 cases of unselected pituitary adenomas, which were surgically removed between 1980 and 1993. All cases were examined by immunohistochemistry and electron microscopy. The mean age of patients was 44.0 years with 40.0 years for women (55.2%) and 49.1 years for men (44.8%). Age distribution indicated a remarkable sex difference: 52.4% of women and 26.8% of men were between 21 and 40 years at the time of surgery. Based on immunohistochemistry and electron microscopy, prolactin (PRL) cell adenomas represented 263% of tumors, growth hormone (GH) cell adenomas 12.5%, adrenocorticotrophic hormone (ACTH) cell adenomas 12.4%, oncocytomas 12,4%, and gonadotroph cell adenomas 9.4%. Seventy-three percent of the prolactinomas occurred in women and 73.8% of the oncocytomas were found in men. The incidence of pediatrics pituitary adenomas was 4.6%. All 647 cases were followed up; the mean follow-up period was 96.6 months. In 40 patients (6.2%), the adenoma recurred. Recurrence was common in functioning ACTH cell adenomas (8 cases: 9.5%) followed by silent adenomas (7 cases: 25.9%). Recurrence was noted after 2-96 months (average 28.7 months) following surgery. The shortest remission period was found in a patient with oncocytoma followed by a patient with prolactinoma.

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PubMed1995

Basic Fibroblast Growth Factor Expression by Two Prolactin and Thyrotropin-Producing Pituitary Adenomas.

We investigated the expression of basic fibroblast growth factor (bFGF) in an aggressive type of PRL and TSH-producing pituitary adenoma. Immunocytochemistry and electron microscopy were used to characterize the tumors removed from two patients. lmmunoassays were used to measure hormone and bFGF levels in vitro and in vivo. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect bFGF mRNA expression by these tumors. Morphologically, these tumors were characterized by an unusual plurihormonal pattern with expression of PRL and TSH and the ultrastructural characteristics of the silent subtype 3 adenoma; in addition, both adenomas displayed marked interstitial fibrosis. bFGF was measurable in the circulation of these patients ranging from 7.5-20.5 pg/mL (normal < 1 pg/mL). bFGF concentrations were reduced following surgical adenomectomy. bFCF in culture media was present in concentrations of 197-387 pg/24h/10(5) cells. bFGF mRNA expression was identified in both adenomas examined. bFGF levels were unaltered in the culture media and in the serum of patients following GnRH and TRH treatment. In conclusion, the expression of bFGF by these plurihormonal pituitary adenomas suggests the possibility that it may play a role in the development of fibrosis and tumor cell proliferation of this unusual type of pituitary neoplasm.

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PubMed1995

The Pituitary in Gigantism.

To compare the pituitary pathology of gigantism to that of acromegaly, 19 surgically resected lesions were studied from 10 males and 9 females, ages 13-49 (mean, 19 yr) with excessive height (>/=95th percentile), onset of disease prior to puberty, elevated growth hormone (GH) levels despite glucose suppression, and a pathologically confirmed GH-producing pituitary mass. One patient had MEN-I. The lesions included 18 adenomas and 1 case of pure hyperplasia. The median, mean, and range of serum GH and prolactin (PRL) levels were 64, 235, 5-1000 ng/mL and 47, 146, 29-770 ng/mL, respectively. Of the 8 adenoma specimens accompanied by nontumoral pituitary (i.e., tissue wherein the presence of hyperplasia was assessable), 3 (37%) demonstrated both. Of the 18 tumors, 78% were macroadenomas and 22% were grossly invasive; their immunophenotypes included GH (5%), GH and PRL (19%), and GHPRL and a glycoprotein hormone, usually TSH and/or a-subunit (76%). Of the 10 adenoma-containing lesions subject to electron microscopy (EM), 2 consisted of GH cells alone; 2 of mammosomatotroph (MS) cells alone; 1 of GH and MS cells; 1 of GH and PRL cells; 2 of GH, PRL, and MS cells; 1 of GH, PRL, and glycoprotein cells; and 1 was a subtype 3 adenoma. Ultrastructurally, GH cells and/or MS cells predominated in these lesions. Immuno-EM of one CH and PRL cell and of one GH-PR-MS tumor showed GH and PRL to be present not only in single cells but within the same granules. Nine of 12 adenoma-associated lesions subject to combined in situ hybridization (ISH) and immunostaining showed double labeling for PRL (or GH) mRNA and for GH (or PRL), respectively, features indicating MS differentiation. In the 4 lesions exhibiting hyperplasia, either alone (1) or in association with adenoma (3), EM showed MS cells in 3, and immuno-EM as well as combined immunohistochemistry and ISH showed double labeling for GH and PRL in both of the 2 cases studied. In summary, although in terms of their tinctorial characteristics and tumor size, the lesions of giants resemble those of acromegalics, those of the former are less often invasive and glycoprotein hormone containing, and more often contain ultrastructurally distinctive MS cells. The high frequency of adenoma with hyperplasia (37%) and the occurrence of hyperplasia alone (6%) is of particular notice since this finding is rare in patients with acromegaly. Hyperplasia is, however, seen in ectopic GH-releasing hormone production and the McCune-Albright syndrome. We conclude that the presence of MS is not rare in the pituitary lesions of patients with gigantism. Their presence may be a reflection of either hypothalamic dysfunction or of an intrinsic abnormality of pituitary cells,

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PubMedDate not supplied

Pituitary corticotroph adenoma containing many apoptotic cells: a histologic, immunohistochemical, ultrastructural and molecular study.

Apoptosis regulates cell turnover in normal tissues and occurs during the neoplastic process. Owing to difficulties in recognizing apoptotic cells by histology alone, several complementary approaches have been introduced, which disclosed the presence of cells with typical nuclear and cytoplasmic changes characteristic of apoptosis. Electron microscopy remains the most conclusive method to reveal the structural changes. Identification of caspase cleaved keratin 18 intermediate filament rearrangements can contribute to the identification of early apoptotic changes. The authors present here an unusual case of a pituitary corticotroph adenoma removed surgically from a young woman with Cushing disease. The tumor contained many apoptotic cells identified by histology. In addition, the apoptotic events were investigated using various morphologic techniques, including electron microscopy, the in situ end-labeling technique, and immunohistochemistry to confirm the caspase-cleaved keratin 18 rearrangements.

Adenoma↗

PubMedDate not supplied

Folliculo-stellate cells of the human pituitary: a type of adult stem cell?

Ultrastructural and immunocytochemical observations of pituitary folliculo-stellate cells (FSC) in a large series of adenomatous and nontumorous human pituitaries led to the following conclusions: (1) The endocrine cells of both the nontumorous and the adenomatous pituitary are capable of transforming into FSC while changing from endocrine to nonendocrine phenotype. (2) As shown on consecutive sections in prolactin cell adenomas with FSC-rich areas including microcyst formation, S-100 protein and glial fibrillary acidic protein (GFAP) immunoreactivities are strongest in the smallest newly formed follicles. The 2 immunoreactivities do not overlap. The epithelium of older microcysts is immunonegative, implying that expression of the 2 markers is restricted to the early phase of FSC formation. (3) Transformation of endocrine cells into FSC may signify retrodifferentiation into their Rathke's pouch derived precursors as suggested by occasional presence of ciliated and/or mucin producing cells in the lining of microcysts. (4) In lymphocytic hypophysitis a marked activation as well as increase of number and size of FSC are evident in areas of ongoing immune destruction supporting their immune role. (5) Considering the multifaceted nature of FSC, it is suggested that they represent a type of pluripotent adult stem cell.

Adenoma↗

PubMedDate not supplied

Effects of medical therapy on pituitary tumors.

Previously surgery and irradiation were the only available procedures to treat patients with pituitary tumors. During the last few decades, novel drugs such as dopamine agonists and long-acting somatostatin analogs were developed and, an alternative medical therapy emerged. This paper summarizes the effect of medical therapy on the morphologic features of pituitary tumors and illustrates the ultrastructural alterations on electron micrographs. Currently drugs can be used in the management of pituitary tumors secreting GH, PRL, and/or TSH in excess. No medical therapy is available so far for ACTH-, FSH-, LH-, or alpha-subunit-secreting tumors as well as non-hormone-secreting pituitary tumors. Dopamine agonists are effective in the management of PRL-secreting tumors; they cause marked reversible tumor shrinkage in the substantial majority of patients. Long-acting somatostatin analogs are useful in the management of GH- and TSH-secreting pituitary tumors; they lead to mild to moderate tumor shrinkage in approximately 50% of cases. In patients treated with these drugs reduction of elevated blood hormone levels and amelioration of clinical symptoms ensue. It should be emphasized that no permanent cure is obtained. Blood hormone levels increase and the clinical symptoms reappear after discontinuation of treatment. Recently GH receptor blockers (pegvisomant) were introduced in the treatment of GH-producing pituitary adenomas. To the authors' knowledge the effect of these drugs on the morphology of pituitary tumors has not been revealed so far.

Dopamine Agonists↗

PubMedDate not supplied

Pituitary hyperplasia.

Pituitary hyperplasia is rare, difficult to diagnose and sometimes controversial. The hyperplasia could be physiologic which is usually reversible, or pathologic which varies in presentation from incidental to tumor like lesion with and without hormonal disturbance. Any pituitary cell is capable of undergoing hyperplasia in the presence of the right stimuli. In this article we summarize the various pathologic and morphologic features of each subtype of pituitary hyperplasia, give an account of the molecular, hormonal and cellular basis of this condition and outline its clinical significance, differential diagnosis and prognosis.

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