Effect of vasoactive intestinal polypeptide (VIP) on growth hormone (GH) and prolactin (PRL) release and cell morphology in human pituitary adenoma cell cultures.

Six GH adenomas and three prolactinomas were investigated by light- and electron-microscopic morphological and immunocytochemical methods and the effect of vasoactive intestinal polypeptide (VIP) on growth hormone (GH) and prolactin (PRL) secretion was tested in vitro. The tumour cells of the acromegalic patients revealed both GH and PRL immunoreactivity while prolactinomas showed only PRL activity. All the adenomas stained immunocytochemically also for VIP. By electron microscopy, the tumours included two densely and two sparsely granulated GH, two mixed GH/PRL, and three sparsely granulated PRL adenomas. The dissociated cells were explanted, and cultured in vitro. The cultures in micro test plates were treated with VIP at different concentrations between 10(-5)-10(-12) M. GH and PRL contents in the culture media were measured by radioimmunoassay. GH release was significantly stimulated by VIP in a dose-dependent manner over the whole concentration range, while VIP was effective on the PRL release only at 10(-6)-10(-7) M concentration. The cells of a mixed adenoma were grown in Petri dishes and used for ultrastructural and immunocytochemical studies. The cytoplasmic structure of the cells treated with VIP corresponded to that of active hormone-secreting cells with large ergastoplasmic fields and Golgi zones containing secretory granules. Massive exocytotic events were encountered mainly in the GH-type cells. GH and PRL double immunocytochemistry showed the predominance of GH cells, many of them containing low amounts of PRL as well. Cells predominantly containing PRL were spread among them, they also might contain GH as well. Some of the cells contained only a single immunoreactive hormone. The intensity of gold labelling of the secretory granules appeared higher in the VIP-treated cells than in the untreated control ones which showed a cytoplasmic structure characteristic of glandular cells with low secretory activity. As all the adenoma cells both contained and reacted to VIP, our results are in agreement with an autocrine or paracrine effect of this peptide. The fine structure of the cells in the cultures treated with VIP supply an additional argument to the assumption that VIP may serve as a growth factor for these cell types.

Primary meningeal melanocytoma of the pineal region. Case report.

A unique case of a meningeal melanocytoma located in the pineal region is presented. This 48-year-old man presented with a round pineal region tumor that caused triventricular hydrocephalus and exhibited slow clinical progression. During surgery a black encapsulated tumor was found and totally removed. On histopathological examination, the tumor proved to be a meningeal melanocytoma. In this report cell culture data are presented and the relevant literature is reviewed. The problems of histopathological diagnosis and management of patients with melanocytomas are also discussed.

Central neurocytoma with malignant course. Neuronal and glial differentiation and craniospinal dissemination.

Central neurocytoma is a benign neuronal tumor of young adults in the lateral cerebral ventricles with characteristic X ray and light microscopic findings. In many respects typical central neurocytoma is reported below, with recurrence in the third month requiring reoperation. Death ensued in the fifth postoperative month. Subsequent histology proved progressive vascular proliferation and increasing, unusual glial differentiation of the neuronal tumor. At autopsy tumorous seeding blocked the liquor circulation. A thin tumorous layer covered the surface of all ventricles, the cerebellum and medulla oblongata. The GFAP positive cells out-numbered the synaptophysin positive ones. Increase of GFAP positivity and vascular proliferation of the central neurocytoma may be alarming signs suggesting a malignant course in addition to the other atypical features.

[The role and importance of CT-guided stereotaxic brain biopsy in neurosurgery. Experiences with 523 cases]. / CT vezérelt stereotaxiás agyi biopszia jelentösége és szerepe az idegsebészetben. Tapasztalataink 523 eset kapcsán.

Between 1989 and 1996, 523 stereotactic biopsies of different intracranial lesions were performed at our institution. In 96.3% of the cases accurate histological diagnosis was made. In 59 cases the drainage of the abscess or cyst was carried out. In 48 cases the lesion was axial, in 27 parasellar, 7 pineal and 37 infratentorial. In the rest of the cases the lesion was in the supratentorial hemispheres. Transient neurological deficits were observed in 3.4% of the cases and craniotomy with haematoma evacuation had to be carried out in one case following the biopsy. There was no mortality associated with the interventions in our material. Our experience supports that CT guided biopsy is a safe and efficient method for obtaining histological diagnosis in different intracranial lesions and showed to be very useful in planning te appropriate treatment for each patient.

Transformation of a human mixed GH-PRL adenoma cell population in response to long-term bromocriptine treatment.

A child was operated 3 times because of a recurrent growth hormone- and prolactin-producing pituitary adenoma. Between the operations she was treated for five years with bromocriptine. The characteristics of the tumour cell population collected after the last operation was now examined by electron microscopy, immunocytochemistry, and in tissue culture and compared to those of the primary tumour cells reported earlier. A prominent change was the reversal of the proportion of the densely and sparsely granulated cells in favour of the GH-type, densely granulated cells. These cells, some of them coexpressing PRL, did not essentially change their characteristics either in vivo or in culture. On the other hand, pleomorphous cells with smaller cytoplasmic area and prominent lysosomal structures represented the sparsely granulated population containing PRL or both PRL and GH. The morphological alteration of the PRL-type cells was also reflected in vitro. Hence, while GH-type cells prevail, at least a sub-population of PRL-type cells survives long-term bromocriptine administration. A shift in the incidence of the two cell types in favour of the GH-type cells explains the change in the endocrine status of the patient.

Granulomatous hypophysitis associated with Takayasu's disease.

We report a case of Takayasu's disease, presenting with symptoms of fever, anaemia, elevated erythrocyte sedimentation rate, anterior pituitary failure and mild diabetes insipidus. A pituitary mass with suprasellar extension mimicking a pituitary adenoma was found, and histological examination revealed granulomatous hypophysitis. The diagnosis of Takayasu's disease was established after the development of a multiple arterial occlusive disease. We suggest that Takayasu's disease should be considered in the differential diagnosis of granulomatous hypophysitis of unknown origin.

Pathological and experimental investigations in a case of gigantism.

A pituitary adenoma was transsphenoidally removed from a 4.5-year-old girl suffering from gigantism. Prior to the operation both the growth hormone (GH) and the prolactin (PRL) levels in the serum were elevated. By light microscopy the tumor appeared to be an acidophilic adenoma. Two distinct cell types, the densely granulated and the sparsely granulated cells, could be distinguished by electron microscopy. Double immunolabeling revealed the presence of GH alone in some densely granulated cells and PRL alone in some sparsely granulated cells, as well as GH and PRL co-localized in both of the morphologically distinguished cell types. Both cell types were identified in the monolayer and the suspension cultures by electron microscopy. GH and PRL concentrations in the culture media were measured by radioimmunoassay. The basal secretion of growth hormone was almost uniform during the 3-week cell culture period. GH and PRL release was significantly inhibited by bromocriptine. Our studies revealed a bimorphous and bihormonal mixed adenoma in childhood.

Pathological characteristics of surgically removed craniopharyngiomas: analysis of 131 cases.

Pathological specimens of 131 surgically removed craniopharyngiomas were obtained from the registry of the National Institute of Neurosurgery, Budapest between 1977 and 1991. The cases were reviewed statistically with reference to their gross and microscopic features and clinical characteristics. Macroscopically, 34% of the tumours were cystic, 23% solid and 43% mixed. Histologically, 38% of the cases belonged to the adamantinous group, 26% were squamous epithelial type, 15% were combined, that is expressing the characteristics of both. In 21% of the cases the surgically removed samples did not contain enough material for correct histopathologic classification. There was no recurrence in the group with the squamous epithelial type tumours, while 59% of the adamantinous, and 36% of the combined craniopharyngiomas recurred. The 5-year survival proportion was 73% at the squamous epithelial, 60% in the adamantinous, and 55% at the combined histological types.

Third ventricle germinoma after total removal of intrasellar teratoma. Case report.

A unique case is presented of a third ventricle germinoma developing 3 years after total removal of an intrasellar teratoma. The third ventricle germinoma was not considered to be a recurrence or dissemination of the mature intrasellar teratoma but to have been transformed from multicenter germ cells present in the midline of the brain with different temporal development. The relevant literature is reviewed and the problems of management of patients with germ-cell tumors are discussed.

Neuropeptides in the human superior cervical ganglion.

Superior cervical ganglia from 7 human cadavers (3-7 h post mortem) were immunostained for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and 14 different neuropeptides. The results show that ganglionic cells contain TH, DBH, neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). These substances were present predominantly within large ganglionic cells. Inside the ganglion, the number and topographical distribution of various types of immunoreactive cells differed from one another. NPY and CGRP immunoreactivities were found in some TH-positive cells, but that co-localization never exceeded the 30% of the TH cells. Leu-enkephalin showed a weak immunoreactivity, which was restricted to fibers or varicosities. Neuropeptides like substance P, dynorphin A and B, cholecystokinin, galanin, corticotropin-releasing factor, thyrotropin-releasing hormone, angiotensin II and neurotensin showed no immunoreactivity in the human superior cervical ganglion.

Secretory component of cystic craniopharyngiomas: a mucino-histochemical and electron-microscopic study.

Ten cases with cystic craniopharyngioma were investigated. Histologically, eight of them belonged to the adamantinomatous group and two were squamous epithelial type. Histochemical investigation revealed mucin secretion in microcysts, and electron microscopy demonstrated zymogen granules in the epithelial cells. When the protein content of the cyst fluid was analyzed by polyacrylamide-gel electrophoresis, the electrophoretic pattern and immunological properties were found to be similar to the normal human serum control. The results of the morphological study suggest that cystic craniopharyngiomas have a secretory component in addition to the classical histological structures.

Primary intracranial sarcomas: histopathological features of 19 cases.

Nineteen primary intracranial sarcomas out of a total of about 25,000 brain tumour biopsies are reported. Subtypes included malignant fibrous histiocytoma (6 cases), leiomyosarcoma (3), rhabdomyosarcoma (2), angiosarcoma (2), and one case each of fibrosarcoma, low-grade fibromyxoid sarcoma, malignant ectomesenchymoma, mesenchymal chondrosarcoma, differentiated chondrosarcoma and Ewing's sarcoma. Histological and immunohistochemical features corresponded to those of extracranial sarcomas. Nests of pleomorphic astrocytes mimicking glioma were detected in the five storiform-pleomorphic malignant fibrous histiocytomas. Our results indicate that intracranial sarcomas can be classified like their extracranial counterparts. The low incidence compared with earlier series is related to changes in classification and progress in histogenetic clarification.

Multi-modality in management of primary malignant non-Hodgkin lymphomas of the central nervous system.

A retrospective study of nine patients with primary malignant non-Hodgkin lymphomas of the central nervous system was carried out with emphasis on treatment results. Detailed investigations before or during the treatment excluded the presence of extraneural malignant lymphoma. The varying radicality of surgery was followed by radiotherapy, with different doses and techniques occasionally with adjuvant drug treatment. Two patients received chemotherapy. Surgical removal and subsequent radiotherapy as well as the histology were almost identical in patients with longer survival. It was tried to evaluate the prognostic influence of different factors on treatment and survival.

Association of primary cerebral lymphoma with meningioma: report of two cases.

Two cases of association of primary malignant cerebral non-Hodgkin's lymphoma with clinically silent meningiomas are reported. In one case, the malignant lymphoma of the left frontal lobe was diagnosed radiographically and the small parasagittal meningioma was detected at autopsy. In the other case, both CNS neoplasms, a parasagittal meningioma and a multifocal periventricular and brainstem lymphoma, were only detected at autopsy. In both cases, the small meningiomas were located at the cerebral convexity. The concurrence of the slowly growing meningiomas and the highly malignant cerebral lymphomas, seen in two among about 140 confirmed cases of primary CNS lymphomas, is probably coincidental. No other neoplasms were found outside of the CNS.

Primary spinal intramedullary malignant lymphoma. A case report.

A rare case of primary malignant intramedullary lymphoma, localized in the cervical part of the spinal cord, is presented. The onset of clinical symptoms was associated with herpes zoster infection. Surgery led to the histological diagnosis. The clinical investigations excluded the presence of lymphoma in other sites in the central nervous system and in the extraneural organs. Postoperative irradiation and chemotherapy effected relict of neurological symptoms.

Intrasellar hamartoma associated with pituitary adenoma.

The histological, ultrastructural and immunocytochemical features are reported of an intrasellar neuronal and lipomatous hamartoma associated with pituitary growth hormone (GH) cell adenoma and acromegaly. Electron microscopy demonstrated a close contact between neurons and adenomatous GH cells. By immunohistochemistry the adenoma cells revealed a positive staining for GH and prolactin. The neurons of hamartoma showed neurosecretory activity which might have induced the development of pituitary GH cell adenoma.

Pathological changes in cystic craniopharyngiomas following intracavital 90yttrium treatment.

Radiosurgery, using 90Y injected directly into the cavity of cystic craniopharyngiomas produces remarkable reduction of tumour size and diminishes cyst fluid production. The authors have studied the histology of biopsy and autopsy material obtained from seven patients presented with cystic craniopharyngiomas. Histological examination was carried out before and after 90Y silicate implantation. As an effect of 90Y irradiation, histology of samples taken from the cyst wall revealed that the lining epithelial cell layer became destroyed and the cyst wall shrunk. Large amount of collagen fibres with focal hyaline degeneration was present. Proliferation of intimal cells and subendothelial connective tissue narrowing small vessel lumina also occurred. Considering that fibrotic tissue is more susceptible to shrink, the fibrosis induced by irradiation together with destruction of the squamous epithelium and vascular changes, might explain the reduction of the cyst volume and diminished fluid secretion after 90Y treatment.

Membranous changes in primary malignant CNS lymphomas.

Ultrastructural studies of 17 primary malignant CNS lymphomas revealed 6 tumors with abnormal intracytoplasmic and/or intranuclear membranous structures, most frequently associated with the endoplasmic reticulum or perinuclear envelope. In most cases, tubuloreticular inclusions and paired cisternae were present. Less frequent were accumulation of microtubules, concentric lamellar bodies, and rod-like or paracrystalline intranuclear inclusions. The specificity and significance of these membranous structures remain questionable because of their frequent occurrence in a variety of normal and pathological conditions. Some of these changes may be considered as cellular reactions to viral infections, others may indicate cellular activity or degeneration.