Katalin Bálint

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.

Long-term results and late complications after intracavitary yttrium-90 colloid irradiation of recurrent cystic craniopharyngiomas.

OBJECTIVE Data were analyzed to assess the value of stereotactically applied intracystic colloidal yttrium-90 (YTx) for the treatment of recurrent cystic craniopharyngiomas during a 30-year period. METHODS This article compares data from 73 YTx procedures in 60 patients between 1975 and 2006. The cumulative beta dose aimed at the inner surface of the cyst wall was 300 Gy. RESULTS After YTx, the initial cyst volumes decreased an average of 79%. In 47, the reduction was more than 80%; in 27 of them, the cyst disappeared completely within 1 year. The mean survival after YTx was 9.4 years (range, 0.7–30 yr). Actuarial survival rates at 5, 10, 15, 20, 25, and 30 years were 81, 61, 45, 18, 2, and 0%, respectively. Late complications of YTx were related to the anatomic localization of the cyst, either presellar and retrosellar, e.g., a presellar (prechiasmatic/suprasellar) localization caused neuro-ophthalmological complications in 5.8% and internal carotid artery injury in 1.6%. The treatment of retrosellar (retrochiasmatic, suprasellar) tumors occasionally induced hypothalamic and/or pontomesencephalothalamic damage obviously by untoward radiation to the so-called perforating arteries. This occurred in 3.2% of these latter patients. CONCLUSION Despite sporadic complications, intracavitary YTx irradiation is a valuable treatment alternative for craniopharyngioma cysts, sometimes as part of a multimodality management in these tumors, especially in precarious surgical cases.

The role of microglia/macrophage system in the tissue response to I-125 interstitial brachytherapy of cerebral gliomas

Abstract Objective: To study histopathologic changes and the role of the microglia/macrophage cell in the therapeutic effect of I-125 interstitial brachytherapy on the cerebral gliomas. Methods: Out of a series of 60 cases with cerebral astrocytomas and other brain tumors treated with I-125 interstitial brachytherapy, autopsy materials were available in ten cases 0.75 and 60 months after irradiation. The patients were treated with the maximum dosage (60 Gy) on the tumor periphery. Besides the routine hematoxylin-eosine and Mallorys PTAH trichrome staining, immunohistochemical reactions were carried out for CD15, CD31, CD34, CD45, CD68, CPM, HAM56 and HLR-DR antigens on paraffin sections to study immunologic phenotypic characteristics of the reaction cell population around gliomas after I-125 treatment. Result: One month after irradiation, a necrotic zone developed around the I-125 seeds within the 72 Gy isodose curve. Histologically, there was a fresh coagulation necrosis in the center of the lesion. Reactive zone has not yet developed but scattered interstitial and perivascular CD68 positive macrophages were present in the surrounding brain tissues. Six months after the I-125 isotope treatment, a reactive zone developed: a microglial rim around the necrosis tissue, and a broad area of proliferating vessels and glial fibrillary acidic protein (GFAP) positive astroglial cells which contained CD68 positive activated microglial and macrophage cells. Fifty-four months after I-125 interstitial irradiation, the necrotic center became colliquative and cystic. The microglial rim was replaced by round end stage (HLR-DR and CD31 positive) macrophages. The reactive zone was characterized by astrocytic gliosis but vascular proliferation and macrophages were lacking. Conclusion: Results of the present immunohistochemical study suggest that the early lesions are characterized by migrating macrophages apparently concerned with the removal of necrotic debris. The established phase of reactive zone around the necrotic center is characterized by a narrow inner rim of microglial accumulation and a broad outer area characterized by astrocytic gliosis, vascular proliferation, activated microglia and infiltration by macrophages. In the burned-out phases of I-125 interstitial brachytherapy of gliomas, the necrosis undergoes liquefaction and the microglial rim is replaced by astrocytic gliosis which can be considered as equivalent to the scar tissue formed around necrosis outside the central nervous system.

Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A in primary breast carcinomas and corresponding distant metastases

Aims To assess the expression of the following cell cycle regulatory proteins in primary metastatic breast carcinomas (MBCs) and on availability in matched distant metastases (DMs): Ki67, cyclin A, geminin and aurora-kinase A (aurkA); and to compare the expression of these markers in early MBC (EMBC) and late MBC separated into groups according to median time point on metastatic event occurred (28 months). Methods The expression of the above mentioned markers was analysed in a total of 47 primary MBCs and 59 DMs (out of which 37 were pairs) by immunohistochemistry. Fourteen breast carcinomas with no relapse over a 10-year follow-up period were utilised as control cases (CBC). Results Among the MBCs, 22 metastasised to the bone, 4 to the lung and 21 to the central nervous system (CNS). Geminin (p<0.001) and Ki67 (p=0.001) were increased in the MBCs while aurkA and cyclin A showed no difference when compared with CBCs. There were no differences between aurkA, cyclin A and geminin expression in MBCs and DMs in general. Expression of Ki67 was, however, elevated (p=0.027) in DMs. In CNS metastases all markers showed elevated expression as compared to MBCs. In bone metastases, geminin was lower (p<0.001) compared with primary MBCs. In the metastases of the lung, the evaluated markers did not show different expression. According to the median follow-up until the metastatic event, Ki67 was found to be significantly elevated in EMBC (p=0.018). Conclusions Ki67 index and geminin distinguish a fraction of MBC with worse prognosis, showing increased levels in the latter in comparison to CBC being tumour-free over a 10-year follow-up period. Ki67 could possibly identify a group of MBCs that develop early DMs.

A needle in the haystack – the dire straits of needle exchange in Hungary

BackgroundThe two largest needle exchange programs (NEPs) in Hungary were forced to close down in the second half of 2014 due to extreme political attacks and related lack of government funding. The closures occurred against a background of rapid expansion in Hungary of injectable new psychoactive substances, which are associated with very frequent injecting episodes and syringe sharing. The aim of our analysis was to predict how the overall Hungarian NEP syringe supply was affected by the closures.MethodsWe analyzed all registry data from all NEPs in Hungary for all years of standardized NEP data collection protocols currently in use (2008–2014) concerning 22 949 client enrollments, 9 211 new clients, 228 167 client contacts, 3 160 560 distributed syringes, and 2 077 676 collected syringes.ResultsWe found that while the combined share of the two now closed NEPs decreased over time, even in their partial year 2014 they still distributed and collected about half of all syringes, and attended to over half of all clients and client contacts in Hungary. The number of distributed syringes per PWID (WHO minimum target = 100) was 81 in 2014 in Hungary, but 39 without the two now closed NEPs.ConclusionsThere is a high probability that the combination of decreased NEP coverage and the increased injection risk of new psychoactive substances may lead in Hungary to a public health disaster similar to the HIV outbreaks in Romania and Greece. This can be avoided only by an immediate change in the attitude of the Hungarian government towards harm reduction.

Pathological findings in cystic craniopharyngiomas after stereotactic intracavitary irradiation with yttrium-90 isotope.

Histopathological, ultrastructural and polyacrylamide gel electrophoretic examinations were carried out on biopsy, cyst fluid, surgical pathology and autopsy specimens obtained from 7 cystic craniopharyngioma cases before and after yttrium-90 silicate colloid (90Y) irradiation. Light microscopy revealed that the lining epithelial tumor cell layer of the cyst wall was destroyed, and scar tissue containing large amount of hyaline degenerated collagen bundles replaced it. Proliferative postirradiation vasculopathy was also demonstrated in the cyst wall following 90Y installation. Electrophoretic property of cyst fluid was similar to the normal human serum. Considering that scar tissue has a certain propensity to shrink, the fibrosis in the cyst wall together with destruction of neoplastic epithelium and vascular changes might explain diminished fluid production and cyst volume reduction after 90Y treatment.

Tissue Response to Iodine-125 Interstitial Brachytherapy of Cerebral Gliomas

The purpose of this study was to investigate histopathological changes and the role of the microglia/macrophage cell system in the therapeutic effect of iodine-125 (125I) interstitial brachytherapy on cerebral gliomas. Out of a series of 60 cases harboring cerebral astrocytomas and other brain tumors treated with 125I interstitial brachytherapy, autopsy material was available in 10 cases between 0.75 and 60 months after irradiation. The patients were treated with 60-Gy maximum doses at the tumor periphery. Besides the routine HE and Mallorys PTAH trichrome staining, immunohistochemical reactions were carried out for CD15, CD31, CD34, CD45, CD68 (PG-M1), CPM, HAM 56 and HLA-DR antigens to study immunological characteristics of the reactive cell population around gliomas after 125I treatment. The present immunohistochemical study demonstrated that the early lesions following 125I interstitial brachytherapy of gliomas are characterized by migrating macrophages apparently concerned with the removal of necrotic debris. The established phase of reactive zone around the necrotic center disclosed a narrow inner rim of microglial accumulation, and a broad outer area consisting of astrocytic gliosis, vascular proliferation, activated microglia and infiltration by macrophages. In the burned-out phase, the necrosis undergoes liquefaction, the microglial rim is replaced by end-stage macrophages, and the reactive zone is transformed into astrocytic gliosis, which can be considered as equivalent to scar tissue formed around necrosis outside of the central nervous system.

Stereotactic Intracavitary Irradiation of Cystic Craniopharyngiomas with Yttrium-90 Isotope

The authors analyzed data from nearly 30-year follow-up period to assess the value of intracavitary irradiation with stereotactically implanted beta-emitting radioisotope yttrium- 90 (90Y) silicate colloid for the treatment of cystic craniopharyngiomas. Seventy-three cysts in 60 patients were selected for retrospective analysis. The cumulative dose aimed at the inner surface of the cyst wall was 300 Gy. An average of 79% (mean 88.3%) shrinkage of the initial cyst volume was observed. In 47 cysts, the reduction was more than 80%, and the cyst disappeared totally in 29 out of those 47 cases, usually within a year. Mean survival duration after intracavitary irradiation was 9.4 years. Neuroophthalmological prognosis was only favorable when the optic disc was normal or nearly normal at the time of the treatment. In the presence of preexisting optic atrophy, visual damage proved to be irreversible. The long-term results support the view that intracavitary 90Y irradiation is a noninvasive and effective method for the treatment of craniopharyngioma cysts. Because of the mean penetration pathway of beta irradiation is 3.6mm in the soft tissues (maximum 11 mm) it cannot influence the solid part of the tumor; therefore, the best result can be expected in solitary cysts.

Image Fusion-Guided Stereotactic Iodine-125 Interstitial Irradiation of Inoperable and Recurrent Gliomas

Between 1996 and 2004, 27 patients with low grade gliomas (WHO grade I-II), 10 patients with WHO grade III gliomas and 6 patients with glioblastoma multiforme (WHO grade IV) were treated with stereotactic brachytherapy using low-dose rate iodine-125 (125I) isotope seeds at the Department of Neurosurgery, St. Johns Hospital, Budapest, Hungary. In all 43 cases, brachytherapy was used for surgically inoperable gliomas: in 32 cases for recurrent gliomas and in 11 cases as a primary treatment. Results of this study suggest that 125I brachytherapy for inoperable and recurrent gliomas is an effective method and offers a chance for longer-term survival.

Angiogenesis and Angiogenic Tyrosine Kinase Receptor Expression in Pediatric Brain Tumors

Tumor angiogenesis and receptor tyrosine kinases (RTK) are major novel targets in anticancer molecular therapy. Accordingly, we characterized the vascular network and the expression pattern of angiogenic RTK in the most frequent pediatric brain tumors. In a retrospective collection of 44 cases (14 astrocytoma, 16 ependymoma and 14 medulloblastoma), immunohistochemistry for VEGFR1, VEGFR2, PDGFRα, PDGFRβ, and c-Kit as well as microvessel labeling with CD34 and SMA were conducted on surgical specimens. We found a significantly higher vascular density in ependymoma. Glomeruloid formations were abundant in medulloblastoma but rare or almost absent in astrocytoma and ependymoma, respectively. C-Kit and VEGFR2 labeled blood vessels were more abundant in ependymoma than in the other two types of tumors. In contrast, medulloblastoma contained higher number of PDGFRα expressing vessels. In tumor cells, we found no VEGFR2 but VEGFR1 expression in all three tumor types. PDGFRα was strongly expressed on the tumor cells in all three malignancies, while PDGFRβ tumor cell expression was present in the majority of medulloblastoma cases. Interestingly, small populations of c-Kit expressing cancer cells were found in a number of medulloblastoma and ependymoma cases. Our study suggests that different angiogenic mechanisms are present in ependymoma and medulloblastoma. Furthermore ependymoma patients may benefit from anti-angiogenic therapies based on the high vascularization as well as the endothelial expression of c-kit and VEGFR2. The expression pattern of the receptors on tumor cells also suggests the targeting of specific angiogenic tyrosine kinase receptors may have direct antitumor activity. Further preclinical and biomarker driven clinical investigations are needed to establish the application of tyrosine kinase inhibitors in the treatment of pediatric brain tumors.