Apoptosis, vascularity, and proliferation in primary central nervous system lymphomas (PCNSL): a histopathological study.

BACKGROUND: In the present study apoptosis, vascularity, and proliferation were quantitatively analyzed with immunohistopathological techniques in primary central nervous system lymphomas (PCNSL). Statistical analysis of these parameters was performed to evaluate their possible relationship with the unfavorable outcome of this tumor. METHODS: A series of 32 PCNSL patients for a total of 33 tumors treated from 1984 to 2000 in the Neurosurgical Department were reviewed, and their histologic specimens examined for apoptosis, vascularity, and proliferation. RESULTS: Patients were treated with either gross total/subtotal tumor removal or stereotactic biopsy. Vascularity was studied by means of FVIII staining, proliferative index with Ki-67 staining, and apoptosis with the TUNEL technique. Most tumors could be classified as immunoblastic or centroblastic B-Cell NHL. Mean Mib-1 Labeling Index was 35.34% (5-80), blood vessel density of 40.8 per 10 high power fields. Apoptotic cells were zero or less than 8 cells per 10 high power fields. CONCLUSION: No statistically significant correlation between survival and histopathological parameters could be shown. However, the apoptosis index was found to be negatively correlated with proliferative index and may account for a more aggressive clinical course of PCNSL.

Xanthomatous hypophysitis mimicking a pituitary adenoma: case report and review of the literature.

Background. Hypophysitis is an inflammatory disease of the pituitary gland that may mimic pituitary tumors clinically and radiologically. Case Description. We report a case of a xanthomatous hypophysitis initially diagnosed as pituitary adenoma. A 31-year-old woman presented with headache, diabetes insipidus, and amenorrhea. A head CT scan showed no intrasellar changes, while an MRI scan showed a sellar cystic mass. An endocrinological work up revealed mild hypocortisolism and diabetes insipidus (DI). Transsphenoidal surgery was performed. The intraoperative histological examination suggested a pituitary adenoma. The removed tissue showed central necrosis surrounded by accumulation of foamy cells and xanthomatous epithelioid cells. The patient made an uneventful postoperative recovery, Nevertheless, DI persisted and the adenohypophysis hypofunction did not recover. Conclusion. We describe an unusual inflammatory lesion of the pituitary gland mimicking an adenoma. A high level of clinical suspicion of inflammatory disorders is necessary for correct diagnosis and optimal management.

Proliferation potential of spinal meningiomas.

OBJECTIVES: The goal of the present study was to quantitatively assess the proliferation index and progesterone receptor status of spinal versus intracranial meningiomas and to determine if these biological indicators can describe the clinical behavior of these tumors. This information could provide the spinal surgeon with important additional information concerning surgical management and follow-up recommendations for the individual patient. METHODS: The study group consisted of 26 patients with spinal and 241 patients with intracranial meningiomas. Patients with atypical or anaplastic tumors as well as with neurofibromatosis type II were excluded from the study. Furthermore both groups were matched according to age, sex and resection grade (total resection according the Simpson classification). Proliferation index (Ki-67 Labelling index [LI]) and progesterone-receptor (PR) status of spinal and intracranial meningiomas were compared. Clinical charts including surgical and histological records and imaging studies were reviewed. Correlations with histological subtype, intratumoral calcifications, tumor vascularity and recurrence-free survival were analyzed. RESULTS: Compared to the spinal group with a mean Ki-67 LI of 2.48% and a positive PR-status of 46%, proliferation rates of intracranial meningiomas were significant higher (Ki-67 LI 3.6%; P-value 0.041). No significant difference in PR status was seen (spinal PR-status 46%, P-value 0.261). Furthermore spinal meningiomas were less vascularized and showed less intratumoral calcifications. Time to recurrence was similar in spinal and intracranial tumors. CONCLUSION: Spinal and intracranial meningiomas differ in their proliferation activity but not in their PR status. However, despite lower proliferation rates, time to recurrence in spinal and cranial meningiomas is comparable in totally excised tumors. Further studies are needed to determine the role of other biological indicators in spinal meningioma growth and response to therapy.

Proliferation and progesterone receptor status in benign meningiomas are not age dependent.

BACKGROUND: Some authors have suggested that the biology of meningiomas differs according to a patient's age. Proliferation, vascularity, and hormonal status in meningiomas can be used to describe changes during aging. In the current study, proliferation activity with the Ki-67/MIB-1 antibody was evaluated by immunohistochemistry in meningioma tissue specimens from young and elderly patients. METHODS: Over the past 25 years, tissue samples from 1766 patients with meningiomas were evaluated. Of these, 588 tumor specimens from 554 patients who underwent surgery between 1990 and 2000 were evaluated immunohistochemically. The proliferation index (LI) and progesterone receptor (PR) in meningiomas were quantitatively estimated in elderly (age > or = 70 years) and young patients (age < 70 years). Patients' charts including surgical records, discharge letters, pathology reports, and imaging studies were reviewed. Correlations with histologic subtype, disease recurrence-free survival, resection grade, location, size, vascularity, and tumor calcification were calculated as well. Only patients with a well documented follow-up were included in the statistical evaluation (n = 385). RESULTS: Compared with the young group of 344 patients with meningioma (age < 70 years; mean age, 51.9 years; range, 18-69 years), the elderly population (age > or = 70 years; n = 41; mean age, 74.9 years; range, 70-88 years) showed a male-to-female ratio of 3.2: 1. Both groups had an identical median Ki-67 LI of 3.0% and a PR status of 56.1% versus 58.4 %. No statistically significant differences in disease recurrence-free survival could be found in the two groups. CONCLUSIONS: Proliferation rates and PR status in benign intracranial meningiomas did not appear to be age dependent.

Biopolymer-mediated suramin chemotherapy in the treatment of experimental brain tumours.

Suramin inhibits tumour growth and neoangiogenesis by blocking several growth factor receptors. In this study the toxicity and efficacy of intralesional delivery of suramin incorporated in a controlled-release polymer were assessed in a rat 9L tumour model. Initially, the toxicity of the compound was evaluated in adult Fisher 344 rats. The animals were intracerebrally implanted with an ethylene vinyl acetate copolymer. These experiments showed early toxicity in the rats implanted with a 50% load-polymer and 100% mortality within 48 h, whereas in rats implanted with a 33% load-polymer only transient behavioural changes were observed. In a second experiment the rats were stereotactically implanted with 9L cells in the frontal region. Two days after inoculation of cells, the animals were divided into two groups: one group received a 33% suramin load-biopolymer at the tumour implantation site, while the control group received polymer implants only. The interstitial release of suramin in the brain did not produce any improvement in survival of 9L tumour-bearing rats, with a mean survival of 14.2 +/- 1 days for the suramin-treated group versus 13.8 +/- 2 for the control group (p = 0.82). We conclude that intralesional polymer-mediated chemotherapy with suramin does not prolong survival in rats with intracerebral 9L tumours.

Intralesional mitoxantrone biopolymer-mediated chemotherapy prolongs survival in rats with experimental brain tumors.

The present study was designed to test the efficacy of intratumoral biopolymer-mediated mitoxantrone chemotherapy in the rat brain 9L glioma model. Mitoxantrone polymers were tested in vitro in 9L and C6 cell cultures for 10 days. Subsequently, adult Fisher 344 rats were implanted with 5 x 10(4) 9L glioma cells in the frontal region of the brain. In a first experiment, 2 days after cells inoculation, one group of rats were implanted with a biopolymer loaded with 4 mg of mitoxantrone at the tumor site. A second group of rats received drug-free biopolymers and served as controls. In a second experiment, rats were implanted with a biopolymer loaded with 2 mg of mitoxantrone. Another group of rats received 2 mg of mitoxantrone intraperitoneally. Controls received drug-free biopolymers. Rats were sacrificed as soon as they developed progressive neurological deficits. In the first experiment mean survival of mitoxantrone-treated rats was 10+/-2 vs. 15+/-2 days for the control group (P = 0.0003). Early morbidity was seen in 60%, and impaired wound healing was seen in 40% of the 4 mg mitoxantrone treated animals. In the second experiment mean survival of mitoxantrone-treated rats was significantly longer than that of the control group (P < 0.0001) with 33+/-7 vs. 13.8+/-2 days for the control group. Only transient early morbidity (20%) was observed at this dose. All rats in the intraperitoneally mitoxantrone-treated group died within the first 4 days after injection. We conclude that controlled-release EVAc carriers deliver biologically active mitoxantrone in a sustained fashion. In vivo biopolymer-mediated mitoxantrone in loco chemotherapy can significantly prolong survival in rats with intracerebral 9L gliomas. Morbidity is mainly dose related, and can be reduced at acceptable levels without compromising the therapeutic effect.