Anaplastic astrocytoma and anaplastic oligodendroglioma occurring 6 years after subtotal resection of a central neurocytoma. Case report

The authors present the case of a 51-year-old man who presented with an anaplastic astrocytoma and anaplastic oligodendroglioma that developed 6 years after subtotal resection of a central neurocytoma in his right lateral ventricle. He had received neither radiation therapy nor chemotherapy after the original resection. On readmission, neuroimaging revealed a mass in the right parietal lobe and a diffuse lesion in the right temporal lobe, insula, and corona radiata. Because both lesions extended to the right lateral ventricle wall, they were regarded as recurrent rather than metachronous tumors. Histological examination revealed anaplastic oligodendroglioma in the parietal lobe and anaplastic astrocytoma in the insula. One year later, the anaplastic astrocytoma was found to have transformed into a glioblastoma multiforme. Fluorescence in situ hybridization analysis and immunohistochemical examinations detected deletions of the lp36 and 19q13 loci, and nuclear accumulation of TP53 protein in the anaplastic oligodendroglioma but not in the glioblastoma multiforme. These findings suggest that central neurocytoma or progenitor cells have the potential for oligodendrocytic and astrocytic transformation with different genetic aberrations.     

Reoperation for recurrent glioblastoma and anaplastic astrocytoma

The advisability of a second operation for recurrent glioblastoma multiforme or anaplastic astrocytoma depends on the expected duration and quality of subsequent survival. We reviewed the results in 70 consecutive patients who underwent reoperation for supratentorial glioblastoma multiforme (n = 39) or anaplastic astrocytoma (n = 31) between 1975 and 1984. The operative morbidity rate was 5.7% (4 of 70 patients); the 6-week postoperative mortality rate was 4.3% (3 of 70 patients). The median duration of survival after reoperation was 36 weeks in patients with glioblastoma multiforme and 88 weeks in those with anaplastic astrocytoma. The median duration of high quality survival (defined as the period during which the patient had a Karnofsky performance score of at least 70) after reoperation was 10 weeks for patients with glioblastoma multiforme and 83 weeks for patients with anaplastic astrocytoma. Age and preoperative Karnofsky score in patients with glioblastoma multiforme and age in patients with anaplastic astrocytoma had statistically significant effects on the duration of high quality survival after reoperation, but not on postoperative survival independent of quality. Although age and functional status do not significantly affect the duration of survival after reoperation, they do have a significant effect on the quality of life after reoperation. Frequently, a patient can expect to spend a greater portion of his life at a higher level of function than he would have without reoperation. As adjunctive forms of therapy improve, reoperation will play an increasingly prominent role in the management of recurrent malignant astrocytic tumors.     

Re-operations of supratentorial anaplastic astrocytomas

Summary Results of re-operations of 99 adult patients with recurrent supratentorial lobar glioblastomas (60 patients) and anaplastic astrocytomas (39 patients) have been reviewed. In all cases both surgical interventions were performed at the same institute. Age of patients with glioblastoma varied between 19 and 64 and with anaplastic astrocytoma between 21 and 68 years, with a mean value of 48 and 36 years, respectively. The median interval between the first and second operations was 47 weeks for patients with glioblastoma and 83 weeks with anaplastic astrocytoma. The mortality rate of the re-operations was 3%. Following re-operation radio-and/or chemotherapy was applied in most of the cases. Median survival time after re-operation was 18.5 weeks in patients with glioblastoma and 55 weeks with anaplastic astrocytoma. Survival curves were calculated according to Kaplan-Meier method and for statistical evaluation the generalized Wilcoxon test and multiple linear regression method were used. Histologically lower grade tumour at the first operation and longer interval between the two operations proved to influence positively and differentiation of the primary tumour negatively the survival time.     

Histologic and clinical factors of prognostic significance in astrocytic gliomas

The three-tiered system of classification of astrocytic gliomas that distinguishes the well differentiated astrocytoma, the anaplastic astrocytoma and the glioblastoma seems to better correlate with outcome. The knowledge of factors (histologic, clinical, radiologic and therapeutic) affecting survival in both well differentiated and anaplastic astrocytomas is limited. In both types young age and high performance status are associated with a better prognosis. The prognostic value of many factors in well differentiated tumors is still debated: this is the case for the number of mitoses, the enhancement on CT, the extent of surgery and the usefulness of postoperative radiotherapy. In anaplastic astrocytomas there is agreement about the prognostic value of endothelial proliferations: their presence is correlated with a poor prognosis. Post operative radiotherapy (5.500-6.000 cGy) significantly improves the survival time, whereas is still not known the true value of the extent of resection.     

Practical Molecular Pathologic Diagnosis of Pilocytic Astrocytomas

The pilocytic astrocytoma is predominantly a tumor of childhood and the most common type of circumscribed astrocytoma. The indolent nature of this tumor allows for prolonged survival for most patients, rendering the disease a rather “chronic” one, with potential long-term sequelae that are occasionally related to treatment. Two critical features of this tumor are its tendency to remain dormant, or involute even after subtotal resection, and the exceptional anaplastic transformation, sometimes following adjuvant therapy. The biological behavior of pilocytic astrocytoma can often be related to molecular alterations in the MAPK pathway.     

Radiation-associated cerebral gliomas. A report of two cases and review of the literature

Two cases are reported in which a cerebral glioma developed after radiation therapy for a different primary tumor. The first case was a boy, who presented a right thalamic anaplastic astrocytoma 7 years after irradiation for a left temporal polymorphic cell sarcoma. The second case was a woman, with a right temporal anaplastic astrocytoma occurring 8 years after irradiation for a GH-secreting pituitary adenoma. Thirty-five other cases of radiation-associated cerebral gliomas had already been reported in the literature. The possible causal role of radiation therapy in inducing cerebral gliomas is discussed on the basis of these observations.     

Adult intramedullary astrocytomas of the spinal cord.

In this series, 25 adult patients with intramedullary astrocytomas were treated by radical excision alone. Six patients proved to have anaplastic astrocytoma; five of them died within approximately 2 years and the sixth has demonstrated disease progression. The other 19 patients were diagnosed as having low-grade astrocytoma (16 cases) or ganglioglioma (three cases); two of these had advanced preoperative neurological disability and died of medical complications. Fifteen of the remaining 17 patients have no clinical evidence of tumor recurrence after a mean follow-up period of 50.2 months; the other two have a small residual neoplasm that demonstrates no progression. Of these 17 patients, seven had previously received radiation therapy, but had clear evidence of tumor growth subsequently. This experience suggests that surgery is not beneficial for anaplastic spinal astrocytoma. However, in cases of low-grade tumor, radical excision is associated with minimal morbidity and an excellent long-term prognosis when carried out before significant disability occurs.     

Recurrent astrocytic tumours--a study of p53 immunoreactivity and malignant progression

Recurrence and progression to higher grade lesions are characteristic of the clinical course of astrocytic tumours. Though p53 gene mutation is an important initiating event in astrocytic tumourigenesis, its role in malignant progression remains controversial. We have therefore analysed p53 protein expression in paired histological samples from 48 cases of astrocytic tumours and their recurrences--29 diffuse astrocytoma, 10 anaplastic astrocytoma and 14 glioblastoma multiforme (GBM). Malignant progression at recurrence was noted in 93% of diffuse and 64% of anaplastic astrocytomas. An association was observed of p53 protein immunopositivity and malignant progression at recurrence. Thus, 27 of 48 (56%) primary tumours were initially p53 positive, while in recurrent tumours associated with malignant progression this frequency increased to 71% (34/48 cases).This was because seven of the 13 cases (4/8 diffuse and 3/5 anaplastic astrocytoma) that were initially p53 negative acquired immunopositivity on malignant progression at recurrence. In contrast, none of the 19 tumours that recurred to the same grade showed any change of p53 status at recurrence. Furthermore recurrence was associated with increase in the percentage of p53 immunopositive cells (p53 labelling index), which was also higher in tumours with progression. This new acquisition of p53 immunopositivity on progression at recurrence has not been documented in earlier studies in English language literature, though increase in p53 LI has been documented. Thus, this study conclusively indicates the role of p53 in malignant progression of astrocytic tumours. Also, it suggests a potential role of p53 LI in predicting malignant progression at recurrence because the highest initial LI was noted in those tumours which progressed to GBM as compared with those which recurred to the same grade or progressed to anaplastic astrocytoma. No correlation could, however, be demonstrated between p53 immunoreactivity and interval to recurrence.     

Preoperative history and postoperative survival of supratentorial low-grade astrocytomas

The preoperative history and postoperative course of histologically verified 348 low-grade and 383 anaplastic astrocytomas have been reviewed. In 71.2 and 48.0% of patients epilepsy was the initial symptom of a suspected astrocytoma, and the history was longer than 3 years in 28.1 and 19.5% of cases, respectively. Before the advent of CT, angiography was performed because of a suspected tumour 2-9 years before surgery in 34 cases. The second angiography years later demonstrated the tumour which in 18 cases at surgery proved to be low-grade astrocytoma or anaplastic astrocytoma in 16 cases. During the last 10 years CT or MRI demonstrated a low-density lesion in 21 patients years before surgery. Operation was postponed for different reasons. Ten tumours appeared at 'delayed' surgery as low-grade, but 11 as anaplastic astrocytoma. In the same period 29 further patients were operated on after a history of seizures, longer than 3 years. Histology showed anaplastic astrocytoma in 10 cases also. Malignant transformation occurred nearly in half of the patients during the observation period. This strongly suggests that dedifferentiation is a spontaneous process, an intrinsic feature of astrocytomas and does not depend on any kind of external stimulus. Another 51 patients' surgery was performed following a shorter (1-24 months) history of epilepsy. The 5-year survival rate was 44 and 39.5% Median survival times (53.5 and 51 months) did not show a significant difference between the two groups, but the total survival, including second survivals after reoperation displayed a significant difference (57.5 vs 67.5 months) in favour of patients with a shorter history of seizures. These experiences confirm the difficulties in decision of the time of surgery. Considering the frequent malignant transformation among patients with a long history of seizures, followed by a relatively shorter survival, it may be supposed that an early radical removal in suitable cases might prevent the late dedifferentiation and recurrence.     

The conditional probabilities of survival in patients with anaplastic astrocytoma or glioblastoma multiforme

BACKGROUND: By the use of conditional probabilities of survival, we studied the yearly survival rates for individual tumor survivors. METHODS: Conditional survival rate was estimated in 114 consecutive patients with anaplastic astrocytoma or glioblastoma multiforme. Conditional probabilities of surviving some years given survival to a specific period of time after craniotomy and 95% confidence intervals were calculated in the individual tumor survivors. RESULTS: The estimated median survival was 30 months for 45 patients with anaplastic astrocytoma and 12 months for 69 patients with glioblastoma multiforme. The conditional probabilities of surviving next one year given survival to 1 year, 2 years, 3 years, 4 years, or 5 years after craniotomy for anaplastic astrocytoma were 86.2%, 75.0%, 85.9%, 77.8%, or 85.7%, respectively; for glioblastoma multiforme 64.8%, 58.7%, 85.7%, 80.0%, or 75.0%, respectively. The conditional probability of surviving to 5 years given survival to 2 years after craniotomy for anaplastic astrocytoma, i.e., surviving an additional 3 years, was 50.1%, which was better than observed 5-year survival rate (28.6%); for glioblastoma multiforme it was 40.2%, which also was better than observed 5-year survival rate (12.4%). CONCLUSIONS: The conditional probability of survival was a good method to clinically predict yearly survival rate for individual tumor survivors. In addition, the method can estimate the probabilities of surviving next some years given survival to a specific period of time after craniotomy. It also showed a more encouraging result than observed survival rate in patients with supratentorial malignant astrocytomas.     

Anaplastic astrocytoma mimicking metastatic carcinoma

A case of anaplastic astrocytoma mimicking a metastatic carcinoma is presented. This rare type of astrocytoma with epithelial features is compared to cases reported in the literature, and the importance of staining brain tumor biopsies for glial fibrillary acidic protein is emphasized.     

Evaluation of radiation therapy in pediatric brain stem glioma by computed tomography: CT findings and tumor response to radiotherapy

The effects of radiation therapy on 29 brain stem gliomas in childhood were evaluated by computed tomography (CT). The patients received radiation of 2 Gy/day as a single fraction, 5 day a week with a total dose of 40 to 60 Gy. Initial CT findings of brain stem gliomas were divided into two types: diffuse and localized. Of 29 children, 5 had localized and 24 had diffuse tumor. Histological diagnoses were available for 18 patients, 4 with localized and 14 with diffuse tumor. All of the localized tumors were astrocytomas and diffuse tumors included 13 anaplastic gliomas (glioblastomas), 3 anaplastic astrocytomas, and one astrocytoma. Complete response or partial response to radiation therapy was observed on CT in 100% (5/5) of the localized tumors and 46% (11/13) of the diffuse tumors at the first evaluation. Contrary to expectation, low-grade gliomas responded much better to radiation therapy than high-grade gliomas. The response rates were 80% (4/5) in astrocytoma, 67% (2/3) in anaplastic astrocytoma, and 38% (5/13) in anaplastic glioma. In the follow-up CT after radiation therapy, a delayed effect was observed in only one of the 24 diffuse tumors. Nine of 10 children who had a re-irradiation following the recurrence experienced very little benefit. None of the patients with localized tumors have shown evidence of tumor progression or recurrence, and the quality of their life has been excellent. On the other hand, all of the patients with diffuse tumor died within 20 months after initial treatment. The results of this study suggest that radiation therapy is beneficial for localized tumors but not for diffuse tumors, and new treatments need to be developed for diffuse tumors.     

Clinicopathological study of diffuse type brainstem gliomas: analysis of 40 autopsy cases

Diffuse type brainstem glioma is one of the most malignant types of brain tumors and the prognosis is extremely poor. The proliferative potential of these tumors is presumed to be very high, but there is little information about the cell kinetics of brainstem glioma because surgical resection is rarely performed. The histological grade, tumor spread, growth potential, and prognosis were evaluated in 40 autopsy cases of diffuse type brainstem glioma. To quantify the growth potentials of individual tumors, the proliferating cell indices of Ki-67 (MIB-1) and proliferating cell nuclear antigen (PCNA) monoclonal antibodies were measured. Mean MIB-1 and PCNA proliferating cell indices were 20.4% (24 cases) and 37.0% (28 cases), respectively, in 34 glioblastomas. The median survival time was 40 weeks in 22 treated patients. The mean PCNA proliferating cell index was 10.8% in four of five anaplastic astrocytomas and the median survival time in four treated patients was 91 weeks. The MIB-1 and PCNA proliferating cell indices of one astrocytoma were 2.9% and 20.3%, respectively, and the survival time was 56 weeks. The overall median survival time was 32 weeks. There was a significant difference in PCNA proliferating cell indices between glioblastomas and anaplastic astrocytomas (p < 0.05) and there was a significant difference in survival time between glioblastomas (40 weeks) and anaplastic astrocytomas plus astrocytoma (74 weeks) among the treated patients (p < 0.05). Supratentorial extension was more frequent in glioblastomas than in anaplastic astrocytomas (p < 0.05). Our results suggest that the majority of diffuse type brainstem gliomas are glioblastoma and the proliferative potential is probably as high as that of adult supratentorial glioblastoma. Supratentorial extension and dissemination are relatively frequent in the advanced stage. Anaplastic astrocytoma or astrocytoma is rarer and less infiltrative and proliferative, and carries a slightly better prognosis than glioblastoma.     

Apoptosis in Astrocytomas with Different Grades of Malignancy

Summary Apoptosis, a form of programmed cell death was studied in astrocytomas with varying stages of malignancy, including low grade astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. Apoptosis was visualized by employing the TUNEL technique and the evaluation of nuclear morphology and this was correlated with a study of bcl 2 expression. A decrease in the percentage of apoptotic cells and bcl 2 expression were evident with increasing malignancy. Furthermore, there was an increase in the proportion of apoptotic cells of the early stage in the more advanced form of astrocytoma. This is a study which demonstrates a possible direct inverse relationship between the severity of apoptosis and the stages of malignancy.     

A case of anaplastic astrocytoma associated with pituitary adenoma

A case of anaplastic astrocytoma associated with pituitary adenoma is reported. The patient was a 33-year-old male, who was admitted with complaints of sensory aphasia, slight left motor paresis, and visual field defects. Neurological examination disclosed sensory and motor aphasia, Gerstmann's syndrome, slight left motor paresis, right homonymous hemianopsia, and bilateral choked discs. Computed tomography revealed a low density mass lesion with slight enhancement in the left temporal region and a ring-like enhanced mass lesion in the suprasellar region. In MRI, both the left temporal and the suprasellar lesions are depicted as low signal intensity areas in T1 weighted imaging, but as high signal intensity areas in T2 weighted imaging. Craniotomy was performed and both tumors were almost totally removed. The tumor in the left temporal region was diagnosed as anaplastic astrocytoma and the other in the suprasellar region was diagnosed as chromophobe adenoma. Multiple primary intracranial tumors of different cell types are rare. About a hundred cases can be found in medical literature. More than two thirds of them are cases of glioma associated with meningioma, but other combinations of tumors are extremely rare. We now report this case of astrocytoma associated with pituitary adenoma. In the literature, there are only 5 cases of similar combination. It is believed that astrocytoma and pituitary adenoma are histologically different. In three of five reported cases, the tumors were in close proximity to each other, but it is doubtful that their close proximity was related to the fact that they developed concurrently.     

Primary cerebellar pilocytic astrocytoma with anaplastic features in a patient with neurofibromatosis type 1 - case report -

A 70-year-old woman with neurofibromatosis type 1 (NF-1) presented with a primary cerebellar pilocytic astrocytoma (PA) with anaplastic features manifesting as worsening headache and ataxia. Magnetic resonance (MR) imaging on admission showed a diffusely enhanced solid mass in the left cerebellar hemisphere, although MR imaging showed no abnormalities 2 years before admission. Histological examination after gross total removal of the tumor exhibited a biphasic pattern with marked Rosenthal fibers, together with some malignant features including frequent mitoses and invasive growth pattern. The final diagnosis was PA with anaplastic features. Previous PA cases with mitotic activity and endothelial proliferation, and/or palisading necrosis have been classified as anaplastic PA (or PA with anaplastic features). In the present case, the tumor histology corresponded to this designation. The present case indicates that PAs with anaplastic features can occur in patients with NF-1.     

Immunohistochemical staining of DNA topoisomerase IIalpha in human gliomas.

OBJECT: The enzyme DNA topoisomerase IIalpha (Topo IIalpha) was tested as a measure of cell proliferation in gliomas. METHODS: Immunostaining for the Topo IIalpha and for the Ki-67 antigen (MIB-1 antibody) was performed in paraffin-embedded tissue sections obtained from 25 resected human gliomas. Additionally, cultured human glioma cells were subjected to simultaneous flow cytometry to determine Topo IIalpha and DNA content. Using flow cytometric analysis, the authors found that the Topo IIalpha antibody labeled cells in the S, G2, and M phases of the cell cycle and also those in some parts of the G0 and G1 phases. In histological sections, Topo IIalpha showed more distinct staining than MIB-1, particularly in older archival cases. The proliferative indices (PIs) based on cells staining for MIB-1 and Topo IIalpha correlated highly with one another (r = 0.96). The Topo IIalpha PI immunopositivity was seen in 4.07% of cells in the low-grade astrocytoma group, 11.97% in the anaplastic astrocytoma group, and 13.84% in the glioblastoma multiforme group, representing significant differences between low-grade astrocytoma and both anaplastic astrocytoma and glioblastoma. A Topo IIalpha PI less than 5% predicted longer patient survival (p = 0.003). CONCLUSIONS: Immunostaining for Topo IIalpha represents a useful alternative to MIB-1 as a proliferative index in human gliomas.     

Fluorescence-guided surgery in high grade gliomas using an exoscope system

Background

Fluorescence-guided microsurgical resections of high-grade gliomas using 5-aminolevulinic acid (5-ALA) is superior to conventional microsurgery. An optical device, usually a modified microscope, is needed for these procedures. However, an exoscope may be implemented for fluorescence techniques. We present the use of an exoscope to perform tumor resection guided by 5-ALA fluorescence in 21 consecutive patients with high-grade glioma and two neuronavigation-guided biopsies.

Methods

Twenty-three patients underwent operations. Tumor volume and localization were quantified with pre- and postoperative volumetric MRI in non-biopsy cases.

Results

In non-biopsy cases, the age range was 20 to 79 years, with a median of 56 (interquartile range?=?45-66). Histological analysis indicated that 14 had glioblastoma multiforme, 2 grade-III oligodendrogliomas and 1 anaplastic astrocytoma, 3 metastases and 1 low-grade astrocytoma. Total resection was achieved in 15 cases; subtotal resection was performed in 5 patients. The result was partial resection in one case. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1–5, was 4.5 in the GBM group (IQR?=?4-5), 3 (IQR?=?2.5-3.5) in anaplastic glioma, and 2.5 (IQR?=?2.25-2.75) for oligodendrogliomas. Of the three metastases, one showed fluorescence level 4. As for the two biopsy cases, one was anaplastic astrocytoma and one glioblastoma multiforme. The samples obtained were fluorescent in both cases.

Conclusions

An exoscope can be also used for fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) and neuronavigation-guided biopsy. With an important advantage of low cost, this allows the surgeon to perform collaborative surgeries and adds agility to the procedure.     

Long-term follow-up results of 175 patients with malignant glioma: Importance of radical tumour resection and postoperative adjuvant therapy with interferon,ACNU and radiation

Summary We analysed long-term follow-up results of 175 patients with malignant glioma (110 glioblastoma and 65 anaplastic astrocytoma) treated under five different regimes during the past two decades. The factors of age (less than 40), histology (anaplastic astrocytoma) and type of adjuvant therapy (radiation and chemotherapy) contributed to long survival. The other important factor was the response to adjuvant therapy.Cases of gross total removal or complete response (CR) of a residual tumour to an adjuvant therapy showed a better prognosis. The three and five year survival rate was 42% and 24%, respectively. The highest CR ratio (23%) was seen in patients treated by intravenous injection of interferon and ACNU in addition to radiotherapy (IAR therapy).     

A case of Ollier's disease associated with two intracranial gliomas

Ollier's disease or multiple enchondromatosis is a deforming dysplastic disease of cartilage involving primarily the metaphyses and diaphyses of long bones. It is only rarely associated with sarcomatous degeneration of the enchondromas or other generalized neoplasms. A related disease, Maffucci's syndrome, is, however, associated with generalized tumors. We present the case of a 29-year-old, albino, black man with Ollier's disease who, as a child, underwent a number of orthopedic procedures for multiple limb deformities and fractures. At age 25, he developed hydrocephalus, progressive cranial nerve palsies, and a large enchondroma of the skull base. He subsequently underwent multiple shunt procedures and two suboccipital craniectomies. Eighteen months later, a brain computed tomographic (CT) scan revealed an intracerebellar mass, which was found to be an anaplastic astrocytoma. Two years later, he developed a right hemiparesis and sensory dysfunction with a diffuse supratentorial mass on CT scan. A stereotactic biopsy showed this to be a similar anaplastic astrocytoma. The literature concerning Ollier's disease is reviewed, and the intracerebral lesions associated with both Ollier's disease and Maffucci's syndrome are examined.