Meningo-cortical calcifying angiomatosis and celiac disease.

A woman with ophthalmic migraine was found to have bilateral cerebellar and cerebral calcifications. She progressively developed severe intracranial hypertension, with swelling of the brain and downward transtentorial and tonsillar herniation. Because steroid treatment was ineffective, the right occipital pole was resected. Histological study demonstrated meningo-cortical calcifying angiomatosis. Within 2 months, brain swelling and papilledema disappeared. Subtle signs of malabsorption led to the hypothesis of celiac disease, confirmed by jejunal biopsy. Similar cerebral histological findings have been reported in the brain of two young patients affected by epilepsy and celiac disease. The association between cerebral calcifications and celiac disease is peculiar; the pathogenetic relationship is unknown.

Long-term follow-up of germinoma after stereotactic biopsy and brain radiotherapy: a cell kinetics study.

The primary aim of this study is to report the long-term outcome of pineal and suprasellar germinoma after stereotactic biopsy and whole brain radiotherapy. The second purpose is to report an investigation of the biological features and cell kinetics of this peculiar and enigmatic brain tumour. Of 34 supratentorial germ cell tumours diagnosed and treated between 1980 and 1993, 20 patients were found to be affected by true germinoma localized in the pineal and/or suprasellar regions. The diagnosis was achieved by stereotactic biopsy in all cases. In 14 patients, the potential proliferative activity of the tumour was investigated by (3H)thymidine in vitro binding and labelling index determination. Chorionic gonadotropin, alpha-fetoprotein and embryonal carcinoma antigen were negative in the cerebrospinal fluid of these patients. All but 1 patient underwent whole brain radiotherapy. Clinical and neuroradiological follow-up ranged between 3 and 13 years (mean 8). Complete clinical and neuroradiological recovery was achieved in all patients after treatment. Fatal recurrences owing to neuraxis dissemination occurred in three cases. The labelling index in the whole series ranged between 0.1 and 5% (median 2.5). Only syncytiotrophoblastic cells had proliferative activity, while none of the lymphoid-like cells showed thymidine labelling.

Medullocytoma (lipidized medulloblastoma). A cerebellar neoplasm of adults with favorable prognosis.

This study describes three cases of neuroectodermal cerebellar neoplasms occurring in adults, characterized by a monomorphic population of round cells with scanty cytoplasm and focal areas of lipid accumulation. Astrocytic and neuronal differentiation was confirmed in these cells by glial fibrillary acidic protein and synaptophysin immunoreactivity. Electron microscopy performed in two cases showed neuritic processes, synapses, and dense-core granules. Patients included two men and one woman, and the age at diagnosis was 36, 37, and 57 years, respectively. Two patients refused any postoperative treatment. One of these had two surgically removed recurrences after 10 and 11 years and died postoperatively from intracranial hemorrhage. The second had two recurrences after 10 and 15 years and is alive and in good health at the last follow-up. The third patient received postoperative radiotherapy and is alive and well after 2 years. Review of the literature revealed seven cases of cerebellar neoplasms with histological features similar to those observed in our series. These lesions have been considered a variant of medulloblastomas. The age of patients ranged from 42 to 77 years (mean age, 51 years); four were women, 3 men. Follow-up information available in two cases indicates a 5-year survival with surgery alone. These data indicate that these cerebellar neuroectodermal neoplasms have morphologically unique features and indolent biologic behavior that distinguish them from the highly aggressive medulloblastoma; the term medullocytoma for this form is suggested.

Low-grade glial tumors in basal ganglia and thalamus: natural history and biological reappraisal.

The natural history of 70 patients affected by low-grade astrocytomas was recorded after the histological diagnosis was obtained by serial stereotactic biopsy. Forty-three percent of these patients died within 3 years. The value of cell kinetics assessment at the time of stereotactic biopsy was investigated, and the labeling index percent may be considered the most accurate prognostic factor in these histologically homogeneous astrocytomas. It has been confirmed that the young age of patients predicts a more favorable course, but the value of this also seems to be linked to and dependent on cell kinetics. These data are discussed in view of the opportunity to perform more aggressive "cytoreductive" treatments in deep brain tumors when these indices support an expected poor prognosis.

Role of stereotactic biopsy in multifocal brain lesions: considerations on 100 consecutive cases.

One hundred patients affected by multifocal brain lesions were investigated by serial stereotactic biopsy. Systemic diseases and primary neoplasms elsewhere were previously ruled out. The histological diagnosis obtained in this series comprises malignant gliomas in 37% of patients; primary non-Hodgkin's brain lymphoma in 15%; metastatic brain tumours in 15% (no evidence of the primary tumour at the time of stereotactic surgery); low grade gliomas in 12%; infective diseases in 10% (including brain abscesses and multifocal viral encephalitis); and ischaemic lesions in 6%. In addition, two patients with germinomas, two with primitive neuroepithelial tumours, two with multiple telangiectases, and one with a teratoma were also included in this series. Histological findings obtained by stereotactic procedures guided the choice of treatment, avoiding the risks of blind treatments. Indications and future perspectives for stereotactic surgery in multifocal brain lesions are discussed with emphasis on advances in diagnostic and therapeutic tools.

Cerebral germ cell tumor and XXY karyotype.

Metaphases from a cultured cerebral germ cell tumor (CGCT) in a boy with a 46,XY constitutional karyotype had 47 chromosomes with an additional X chromosome and a translocation (1;21)(q11;p11). CGCT appear to be nonrandomly associated with Klinefelter syndrome, and a supernumerary X chromosome and trisomy of the 1q21-->1qter region may be clonal abnormalities in these tumors. The predisposition of Klinefelter patients to develop CGCT may be due to the pathogenetic relevance of the extra X chromosome both as an acquired and a constitutional abnormality.

Intracranial dissemination of pituitary adenoma. Case report and review of the literature.

Leptomeningeal dissemination of pituitary adenoma is a very rare occurrence. The present report describes the case of a 28 year old man with a nonfunctioning pituitary adenoma which was operated on and irradiated. Eight years later, the patient developed Cushing's syndrome and multiple leptomeningeal masses were revealed by brain CT and MNR. The diagnosis was ACTH-cell adenoma, without malignant histological signs. The growth fraction of the tumor, detected by means of the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA), was 5.45% of cells; this figure is higher than that reported for non-recurrent pituitary adenomas. From a review of the reported cases, the possibility of predicting late malignant behaviour is discussed. The microscopic aspect has no prognostic value, since metastasizing cases are not overtly malignant in a histological or cytological sense. The application of methods aimed at detecting the growth fraction of the tumor may prove useful in the early identification of aggressive pituitary tumors.

Chemotherapy as first treatment for primary malignant non-Hodgkin's lymphoma of the central nervous system preliminary data.

Non-Hodgkin's lymphoma of the central nervous system (NHL-CNS) is thought to account for about 1% of primary brain tumours. Radiation therapy has mainly been applied to treat cerebral lymphoma, but the low cure rate and the lack of enduring response have stimulated the search for alternatives. With the aim of postponing radiotherapy as long as possible, we tested the efficacy of a M-BACOD schedule administered immediately after histological diagnosis in 14 patients. After two M-BACOD courses 10 (71%) patients displayed an objective response (i.e. were apparently tumour-free when examined by CT). In 6 (60%) M-BACOD-responsive patients, radiotherapy was delayed for 5 months (without recurrences after a follow-up ranging from 9 to 18 months). Moreover, in 3 M-BACOD-responsive patients, no recurrence took place (even without radiotherapy) after a follow-up of 6-12 months. We conclude that radiation can be postponed after chemotherapy or delayed until tumor recurrence.

p53 protein expression in central nervous system neoplasms.

AIMS: To demonstrate, immunohistochemically, p53 protein expression in a selection of central nervous system tumours; to investigate the relation between p53 expression and that of the proliferation related antigen, PCNA. METHODS: Surgical specimens from 86 central nervous system tumours were routinely fixed, paraffin wax embedded, and immunostained with a monoclonal (PAb 1801) and a policlonal antibody (CM1) p53 protein and a monoclonal antibody against PCNA (PC10). Normal brain samples obtained at necropsy and 10 surgically obtained samples of gliotic brain parenchyma were also immunostained. RESULTS: p53 protein expression was observed in 35 of 86 brain tumours, suggesting frequent p53 gene mutation. p53 protein alterations were associated with all grades of malignancy in tumours displaying solely astrocytic differentiation, with the exception of pilocytic astrocytomas. In those showing oligodendroglial or ependymal differentiation they appeared to be restricted almost to only high grade lesions. No p53 immunoreactivity was observed in normal or gliotic brain tissue; p53 altered expression was not related to the percentage of PCNA labelled cells. CONCLUSIONS: The use of sophisticated gene amplification techniques or highly sensitive immunohistochemical methods might be useful in distinguishing between reactive and neoplastic astrocytic lesions, and in the identification of malignant progression in other non-astrocytic glial tumours. Tumours with very similar histogenetic differentiation features might actually be a genetically heterogeneous group with possible different clinical courses.

Cerebromeningeal pleomorphic xanthoastrocytoma. Report on four cases: clinical, radiologic and pathological features. (Including a case with malignant evolution).

Three cases of cerebromeningeal pleomorphic xanthoastrocytoma are presented and the recurrence of a fourth case, previously described in 1980, is examined because of its evolution towards malignancy. Clinical, radiologic and pathological aspects are discussed and the general features of the previously reported cases of xanthoastrocytoma are reviewed.

Proliferating cell nuclear antigen expression in central nervous system neoplasms.

Proliferating cell nuclear antigen (PCNA) is a cell-cycle-regulated protein, which can be demonstrated in routinely fixed specimens. Studies on various tissues, cell cultures and neoplasms have shown that PCNA labelling index (LI) correlates with flow cytometry, tritiated thymidine LI, bromodeoxyuridine (BrdU) incorporation and Ki67 LI. PCNA LI may have prognostic value in various neoplasms. The present study concerns PCNA immunostaining in a series of neuroglial tumours. We demonstrate that there is a relation between PCNA LI and histological grade, and between PCNA LI and reported thymidine LI, BrdU LI and Ki67 LI. Pleomorphic xanthoastrocytomas and low-grade astrocytomas had the lowest LI, whereas metastases of small cell lung cancer and medulloblastomas had the highest LI. Glioblastomas sometimes showed a certain degree of intratumoral heterogeneity of distribution of immunostained cells. Intratumoral heterogeneity underscores the critical importance of representative sampling of central nervous system neoplasms for kinetic studies. As expected, PCNA LI are somewhat higher than tritiated thymidine LI, BrdU LI and Ki67 LI because PCNA is a marker of G1, S, G2 and M-phases of the cell cycle and not of S-phase only. In addition, because of its long half-life, PCNA may be detected immunohistochemically in cells that have recently left the cell cycle. The immunohistochemical evaluation of PCNA LI is easy to perform on routinely processed material, allowing retrospective studies. PCNA LI may be a useful tool in grading gliomas. However, its prognostic value must be validated by comparing PCNA LI with the follow-up of the neoplasms, and possibly with the responsiveness to anti-proliferative therapy.

Cerebral ganglioglioma with anaplastic oligodendroglial component.

We report an unusual and possibly unique example of cerebral ganglioglioma with an anaplastic oligodendroglial component. The latter was documented on both morphological and immunohistochemical grounds. Immunohistochemically, the anaplastic cells were strongly positive with the monoclonal antibody anti-Leu-7, while they lacked glial fibrillary acid protein, vimentin and neurofilaments.

Amelanotic leptomeningeal melanoblastosis. Case report.

Leptomeningeal melanoblastosis is a rare phakomatosis; the amelanotic variant has not till now been described. In this paper we report the case of a young man suffering from amelanotic leptomeningeal melanoblastosis manifested as medullary syndrome and secondary intracranial hypertension. The diagnosis of leptomeningeal melanoblastosis was hypothesized on the basis of CSF and neuroradiological findings and it was finally confirmed by the histopathology.

Cerebral multiple glio-vascular dysplasias--a case report.

We describe the clinical and neuropathologic features of a patient complaining of increased intracranial pressure lasting over two years. Brain CT showed three cystic lesions in the supratentorial regions. Autopsy disclosed multiple small glio vascular abnormalities, in some instances connected with a cystic cavity. The lesions were scattered throughout the white matter of both cerebral hemispheres and suggested a complex dysplasia.

[Magnetic resonance in brain tumors: a classification based on signal behavior in multiple echo sequences]. / La Risonanza Magnetica nei tumori cerebrali: classificazione in base al comportamento di segnale nelle sequenze in multieco.

MR is generally known to be more sensitive but less specific than CT in the detection of brain lesions. In our opinion multiple echo sequences can markedly improve MR specificity in the diagnosis of tumors. We reviewed a series of 343 intracranial tumors studied with MR using multiple echo sequences and histologically verified. On the basis of the different signal patterns we divided brain tumors into 5 classes. Class 1: the signal intensity of the tumor increases progressively in T2 WI (100% of craniopharyngiomas, 21/21; 100% of epidermoid tumors, 12/12; 81% of astrocytomas (grades I to III), 64/79; 65% of neurinomas, 30/46). Class 2: the signal intensity of the lesion decreases progressively in T2 WI: A) the tumor has higher signal intensity than the parenchyma in all echoes (100% of medulloblastomas, 14/14; 53% of pituitary adenomas, 15/28); B) the tumor has the same signal intensity as the parenchyma in late echo acquisitions (100% of ependymal tumors, 12/12; 60% of meningiomas, 25/41). Class 3: the tumor has the same signal intensity as the parenchyma in all echoes (34% of meningiomas, 14/41). Class 4: glioblastoma model: one or more cysts of high signal intensity in T2 WI and slightly hyperintense nodules and/or rings and hyperintense peritumoral edema (73% of glioblastomas, 35/48; 72% of metastases, 18/25). Class 5: oligodendroglioma model: mixed hyper/hypointense pattern; cyst, calcifications and edema are very difficult to recognize within the lesion (95% of oligodendrogliomas, 18/19). The signal pattern was sometimes characteristic but never pathognomonic. Nevertheless, this classification proved to be an useful criterion to restrict the number of possible diagnoses. The study of T1 and T2 values seems to be less useful.

Cell kinetic investigations in brain tumors studied by serial stereotactic biopsy.

Between July 1983 and July 1986, 109 consecutive patients affected by brain tumors and selected for stereotactic biopsy underwent in vitro investigation of cell kinetics. The potential proliferative activity of these different neoplasms, evaluated as in vitro 3H-thymidine labeling index (LI), has been determined in 46 mature astrocytomas, 19 anaplasic astrocytomas, 25 glioblastomas, 5 cystic craniopharyngiomas, 6 metastatic tumors, 4 primary C.N.S. lymphomas, 3 pineal germinomas and one choroid plexus papilloma. The relevance of LI on prognosis has been evaluated in 35 patients affected by glial tumors with adequate follow-up longer than 2 years. This retrospective study allowed us to demonstrate the prognostic value of LI in mature astrocytoma and anaplasic astrocytoma series. The feasibility of LI determination by in vitro procedure has been demonstrated also in non-neuroectodermal tumors. In craniopharyngioma the LI investigations allowed to demonstrate a peculiar topographic arrangement of cells in S phase.

Sialidosis type I: pathological study in an adult.

Histological and ultrastructural findings observed throughout the nervous system and the extranervous organs in a case of sialidosis type I, also known as normosomatic group, are reported. The patient was a 22-year-old male with non-familial progressive myoclonus, macular cherry-red spot, moderate cerebellar syndrome and normal intelligence. Biochemical study showed an alpha-N-acetylneuraminidase deficiency in cultured fibroblasts. A complete and early autopsy was performed. Neuropathological study showed two prominent lesions: the first one was a fine cytoplasmatic vacuolation in several neurons of the cortex, basal ganglia and thalamus and the second one was a diffuse neuronal intracytoplasmic storage of lipofuscin-like pigment (LLP). As for the extranervous organs the main light and electron microscope findings were observed in the hepatocytes and in the Kupffer's cells, which showed an enlarged cytoplasm and lipopigment granules in different amount. Vacuoles containing dense lamellar bodies were found in tubular epithelial cells of the kidney. To our knowledge this is the first complete autoptic study of a case of sialidosis type I.

Familial frontal lobe oligodendroglioma. Case report.

Two cases of frontal bilateral oligodendroglioma invading the corpus callosum occurred in a 56-year old man and his 32-year old son. CT images of both patients are presented.

Two familial cases of Creutzfeldt-Jakob disease in Italy.

Two familial Italian cases of Creutzfeldt-Jakob disease are reported. Clinical picture and life history are presented and compared: 1) with the findings in familial cases reported in other countries, 2) with the findings (age at onset, disease duration) in sporadic Italian cases.