Aspergillus terreus brain abscess mimicking tumor progression in a patient with treated glioblastoma multiforme.

OBJECTIVE: To detail a case of Aspergillus terreus brain abscess in a patient undergoing treatment for malignant glioma. Central nervous system aspergillosis usually occurs in patients with hematopoietic neoplasms or post transplantation, not in those with solid tumors. Most systemic invasive mold infections are attributable to Aspergillus fumigatus or Aspergillus flavus. PATIENT AND METHODS: The patient had received external beam radiation, temozolomide chemotherapy, and high-dose steroids, and had lymphopenia, but not sustained neutropenia. She developed a brain mass that mimicked tumor progression by neuroimaging criteria; infection was not a consideration. RESULTS: Brain biopsy showed fungal cerebritis and cultures grew A. terreus, a variant being reported with greater frequency as a pathogen in patients with risk factors for aspergillosis. CONCLUSION: Brain tumor patients who receive steroids to control their peritumoral edema may be particularly susceptible to cerebral A. terreus infection, especially when they additionally develop the lymphopenia commonly associated with temozolomide.

Benign cylindroma causing transcalvarial invasion in a patient with familial cylindromatosis.

OBJECTIVE: To describe a case of scalp cylindroma without features of malignancy invading through the skull and dura, and producing massive intracranial extension. Tumors of epidermis and epidermal appendages rarely show bony invasion, but invasive tendency in some tumor types has been associated with increased TP53 expression. PATIENT AND METHODS: Patient with familial cyindromatosis (Brooke-Spiegler syndrome) who had undergone numerous previous surgical excisions over the past 30 years of his scalp cylindromas. Light microscopic and immunohistochemical characterization of resected tumor, with TP53 immunostaining in the invasive tumor was compared with that seen in five other cutaneous, non-invasive cylindromas. RESULTS: Tumor showed no increase in mitotic rate or increased immunostaining for TP53. CONCLUSION: Multiple previous surgeries down to pericranium may have contributed to local weakening of tissues and facilitated transcalvarial invasion. While an uncommon occurrence, both benign and malignant cylindromas have the capacity to invade bone, particularly in patients with the familial syndrome.

Secondary central nervous system involvement by follicular lymphoma: case report and review of the literature.

BACKGROUND: We report a patient with indolent stage IV follicular lymphoma, grade 1, initially successfully treated with chemotherapy, who later developed aggressive diffuse large B-cell lymphoma in the parieto-occipital lobe 8 years after initial presentation. The differing patterns of lymphomatous involvement of the central nervous system (CNS) are briefly reviewed, with a focus on the patterns seen in secondary CNS spread by low-grade lymphomas. CASE DESCRIPTION: A 53-year-old man was diagnosed with stage IV follicular lymphoma, grade 1, in 1996. Although initial chemotherapy was successful, he developed several recurrences of lymphoma over the following years. In May 2004, he presented with a discrete, single, massive parieto-occipital lobe brain lesion. The mass failed to regress with empiric cranial external beam radiotherapy. Because of suspicion of an unusual infection, the lesion was surgically excised in its entirety. The mass proved to be an aggressive diffuse large B-cell lymphoma, transformed from his previous follicular cell lymphoma, with retention of strong Bcl-2 and Bcl-6 immunoreactivity. CONCLUSIONS: Parenchymal brain involvement, as opposed to dural or leptomeningeal, is a relatively uncommon pattern of spread to the CNS for systemic lymphomas. More significantly, follicular lymphomas are one of the least frequent types of indolent lymphomas to develop clinically apparent, secondary CNS spread. The presentation of an indolent follicular lymphoma with transformation to an aggressive diffuse large B-cell lymphoma within the brain parenchyma is rare. Its manifestation as a massive, singular lesion is unique and prompted diagnostic confusion.

Glioblastomas in the older old.

CONTEXT: Recent studies have identified fundamental biological differences in the effects of epidermal growth factor receptor (EGFR) amplification on survival in older versus younger patients with glioblastoma multiforme (GBM). Cell cycle labeling indices have also been found to be inordinately high in older GBM patients and may contribute to the known adverse prognosis in this cohort. However, testing has not been conducted on significant numbers of patients of very advanced age, in whom these features might be expected to emerge as even more significant factors. OBJECTIVE: To assess EGFR amplification status and MIB-1 indices in patients with GBM who are older than 75 years. DESIGN: We identified 20 patients (female-male ratio, 11:9; 11 aged 75-79 years and 9 aged 80-87 years) and studied tumor tissue samples with immunohistochemistry for cell cycle labeling index and by fluorescence in situ hybridization for EGFR amplification. Survival data were obtained from the Colorado Tumor Registry. RESULTS: Mean MIB-1 index was high (24.8%), but individual indices did not correlate with survival. EGFR amplification was detected in 25% of cases, with gain of chromosome 7 in all but one of the remaining patients. Ninety-five percent of patients manifested EGFR amplification and/or polysomy of chromosome 7. Heterogeneity was found within a given tumor, with 10% to 60% of cells showing gain of chromosome 7. Overall patient survival was poor (mean, 4.6 months), but was significantly longer in those with EGFR gene amplification (mean, 8.3 months; median, 10.5 months) versus those without (mean, 3.2 months; median, 2.0 months) (P = .04). CONCLUSION: The presence of EGFR amplification is a significant predictor of survival time in older old patients.

Neoplasms involving the central nervous system in the older old.

Geriatric cancer patients present special challenges for clinicians. Few large series have been published in the last 20 years on the types of neoplasms that involve the central nervous system (CNS) in older individuals. To review types of neoplasms involving the central CNS that are currently being encountered by pathologists and neurosurgeons, we identified from our databases for the years 1992-2002, inclusive, patients 75 years or older who had symptomatic lesions requiring neurosurgical interventions. Retrospective characterization of tumors by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization was performed whenever possible and relevant to tumor type. Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients were diagnosed as having neoplasms, with clot evacuation or infections being the most frequent non-neoplastic conditions necessitating surgery. Tumor types included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12), lymphomas or other hematological malignancies (8), anaplastic gliomas (5), metastases (6), head and neck malignancies with direct intracranial extension (3), and other miscellaneous tumor types (4). Compared with older literature series, we encountered a larger number of elderly patients with CNS lymphomas and fewer who came to surgery for CNS metastatic disease. In the "older old", glioblastomas are the most frequent symptomatic tumors necessitating surgical intervention. Glioblastomas in this aged cohort display the signature features of the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1-labeling index=25.1%), and either amplification of epidermal growth factor receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of assessable cases).

Overcoming MDR by ultrasound-induced hyperthermia and P-glycoprotein modulation.

We assessed the effects of combining ultrasound-induced hyperthermia (USHT) with the P-glycoprotein modulator PSC 833 on cellular retention and cytotoxicity of rhodamine 123 (R123) and doxorubicin in the parent and multidrug resistance (MDR) variants of two human cancer lines. USHT significantly increased cellular uptake of R123 and doxorubicin. Without PSC 833, release of R123 and doxorubicin from both USHT-treated and untreated cells was rapid. As expected, PSC 833 (0.5 microM) only slowed their release into the MDR lines. Interestingly, despite the differences in their starting amounts, PSC 833 was effective in prolonging R123 and doxorubicin release from both USHT-treated and untreated MDR cells. PSC 833 did not augment the cytotoxicity of doxorubicin in parent lines but did cause a significant increase in cytotoxicity of doxorubicin in the MDR lines. However, the combined effect of USHT and PSC 833 on cytotoxicity of doxorubicin far exceeded that produced by USHT or PSC 833 alone.

Ultrasound-Induced hyperthermia increases cellular uptake and cytotoxicity of P-glycoprotein substrates in multi-drug resistant cells.

PURPOSE: Localized hyperthermia has been shown previously to augment the cytotoxicity of some lipophilic anticancer drugs. Because many of the substrates for the multi-drug resistance (MDR) transporter P-glycoprotein (P-gp) are lipophilic in nature, studies were conducted to test the hypothesis that hyperthermia induced by ultrasound could also increase cellular uptake and cytotoxicity of P-gp substrates by P-gp-expressing cells. METHODS: To test this hypothesis, we studied the effects of hyperthermia and ultrasound on cellular accumulation of putative P-gp substrates, rhodamine 123 (R123) and doxorubicin (DOX), and cytotoxicity of DOX in the parent and MDR variants of two human cancer cell lines. RESULTS: Treatment of cells with hyperthermia or ultrasound (20 min at 41 degrees C) both caused a significant increase over controls (no ultrasound treatment) in R123 and DOX accumulation in the parent and MDR lines of MV522 and KB cells. Ultrasound also substantially increased the antiproliferative effects of DOX in both the parent and MDR variants of MV522 and KB cell lines when compared with controls. Our results also indicated that ultrasound exerted a much greater effect on cellular accumulation of R123 and DOX and cytotoxicity enhancement of DOX in the MDR variants than putative P-gp antagonist such as verapamil. CONCLUSION: The present results point to the potential use of ultrasound-induced hyperthermia as a much safer alternative to P-gp antagonist for reversal of MDR.

A threshold concept for cancer therapy.

Oxygen free radicals have been implicated in many disease processes, including aging and carcinogenesis, and have been associated with a variety of complications resulting from the treatment of cancer. As a result, the treatment of free radical-induced disease with antioxidants or free radical scavengers has become an important therapeutic modality. Ironically, these same oxygen free radicals also play a critical role in anti-cancer therapies. The use of antioxidants such as superoxide dismutase (SOD), in this setting, has been found to decrease the efficacy of anti-tumor therapies, which depend on free radical generation for their action. In addition, increased antioxidant activity can often be utilized by the tumor cell to favor increased growth. Therefore, the appropriate application of oxygen free radicals and antioxidants seems to be critically important in designing proper strategies for both prevention and treatment of malignant disorders. This review will summarize free radical and antioxidant regimens that have been employed to date, examine some of the problems associated with these regimens, introduce the 'threshold concept' explaining the dual effects of oxygen free radicals and antioxidants, and discuss a novel hypothesis regarding therapy that could potentially improve outcome in cancer patients.

Sinonasal teratocarcinosarcoma ("mixed olfactory neuroblastoma-craniopharyngioma") presenting with syndrome of inappropriate secretion of antidiuretic hormone.

Sinonasal teratocarcinosarcoma (SNTC) is a rare, aggressive, histologically heterogeneous neoplasm of the paranasal sinuses and nasopharnyx of adults that is composed of variably benign or malignant neuroepithelial, epithelial, and mesenchymal elements. Occasional cases show intracranial extension and may be operated on by neurosurgeons and encountered by neuropathologists who may not be familiar with the entity. STNCs have not previously been associated with functional hypersecretory status. We report a 59-year-old male who presented with headache and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and was subsequently found to have a bulky tumor of the frontal and ethmoid sinuses with focal dural invasion. The tumor was predominantly composed of olfactory neuroblastoma areas (90% of tumor) admixed with unusually well-developed craniopharyngioma-like mature squamous epithelium and ghost cells ( 10% of tumor). Scattered neuroblastoma tumor cells showed strong immunoreactivity with antibodies to arginine vasopressin, supporting ectopic hormone secretion by the tumor. While the coexistence of neuroectodermal and oral ectodermal-like differentiation in SNTCs is characteristic, in our case it was developed to an extreme functional and morphologic degree and was unassociated with other mesenchymal or epithelial elements often found in these complex tumors. SNTCs with limited differentiation have prompted controversy in classification.

Time course analysis and modulating effects of established brain tumor on active-specific immunotherapy.

OBJECT: There have been numerous attempts to establish an effective immunotherapy for the treatment of brain tumors. To date, reliable methods to manipulate the immune system for promoting brain tumor regression have been disappointing. Generation of active immune responses in most of these studies was only possible in the absence of viable tumor cells, suggesting that immunotherapy can only be used as preventive therapy. In few studies the investigators have demonstrated success in using immunotherapy to treat a preestablished intracranial tumor. Using the 9L intracranial glioma model, the authors sought to delineate the underlying mechanisms for these observations. METHODS: In animals vaccinated with irradiated 9L glioma cells and interferon-gamma 14 and 7 days prior to intracranial tumor cell challenge, a significant increase in survival was shown. In contrast, vaccinations applied 3 days prior to, at the time of (Day 0) or 7 days after intracranial tumor cell challenge failed to influence survival. Histological examination of brain tissue specimens obtained in animals vaccinated before or after tumor cell challenge showed no difference in the degree of peritumoral mononuclear cell infiltration. When activated spleen cells obtained obtained from these animals were assayed for cytotoxicity and proliferative capacity, only those spleen cells derived from animals vaccinated prior to intracranial tumor cell challenge showed enhanced activity. CONCLUSIONS: These data support the presence of a strong modulatory effect of tumor on local and systemic antitumoral immune response. This immunosuppression appears to be secondary to a direct effect on T-cell function. Reversal of this immunosuppression may be a useful adjunct to tumor vaccine therapy.

Current perspectives in immunotherapy.

Since the declaration of the war on cancer in 1971, our ability to effectively treat cancer has been less successful than anticipated. Surgery and radiation therapy remain our most effective treatment modalities, with chemotherapy proving beneficial in only a limited number of tumor types. The reality of this poor response to conventional therapy has prompted a search for other potentially beneficial therapies. The idea of using the immune system to eradicate tumor is not new. Over 100 years ago, William Coley (in 1893) first reported on the ability to induce tumor regressions by nonspecific activation of the immune system in response to bacterial toxins. Despite this early beginning, efforts to reliably manipulate the immune system to promote tumor regression has been universally disappointing. With recent advances in our understanding of the immune system, and the identification and availability of numerous growth promoting and growth-suppression cytokines, the concept of immunotherapy being a useful therapeutic intervention for the treatment of cancer is becoming a reality. Immunology in general, and tumor immunology specifically, are fields foreign to the practicing tumor surgeon. As progress in these fields are made, it will become important for the surgical oncologist to have a better understanding of tumor immunology as it relates to therapy. This paper reviews our current understanding of the immune system as it relates to cancer immunotherapy (using primary intracranial glioma as the tumor model), and then relates this knowledge to recent work in the development of tumor-specific vaccines.

Reverse transcription polymerase chain reaction analysis of pituitary hormone, Pit-1 and steroidogenic factor-1 messenger RNA expression in pituitary tumors.

Pit-1 is a transcription factor that appears early in embryonic pituitary gland formation and is necessary for the development of somatotropes, lactotropes and thyrotropes. Steroidogenic factor-1 (SF-1) is another early appearing transcription factor that is involved in the development of gonadotropes. In this study we have compared RT-PCR analysis of hormone mRNA with traditional IHC for classification of 27 pituitary tumors and have evaluated the correlation of Pit-1 and SF-1 mRNA with hormone mRNA. RT-PCR detected concordant hormone mRNA in 100% of GH IHC positive, 100% of PRL IHC positive, 33% of TSH IHC positive, and 93% of gonadotropin IHC positive tumors. IHC, however, was concordant in only 71% of GH mRNA positive, 78% of PRL mRNA positive, 17% of TSH beta mRNA positive, and 76% of FSH beta mRNA positive tumors. Pit-1 mRNA was positive in 87% of tumors in which mRNA for GH, PRL or TSH beta was detected and in only 17% of GH, PRL and TSH beta mRNA negative tumors. SF-1 mRNA was positive in 94% of tumors in which mRNA for FSH beta was present and in no FSH beta mRNA negative tumors. We conclude that RT-PCR analysis of hormone mRNA may be more sensitive than traditional hormone IHC for classification of pituitary tumors. Furthermore, tumor Pit-1 mRNA positively correlates with GH, PRL and TSH beta mRNA while tumor SF-1 mRNA correlates well with FSH beta mRNA. Combined analysis of hormone and transcription factor mRNA in pituitary tumor tissue may therefore be a more meaningful approach to pituitary tumor characterization.

Cavernous angiomas of the cauda equina: case report and review of the literature.

BACKGROUND: Cavernous hemangiomas of the spine and spinal cord are relatively uncommon lesions that are being discovered more frequently because of the increased use of magnetic resonance imaging (MRI). We present a rare case of a symptomatic cavernous hemangioma of the cauda equina. CASE DESCRIPTION: A 49-year-old woman presented to our institution with the chief complaint of low back pain of acute onset. On physical examination the patient was found to be tender to percussion over the lumbar spine, had tenderness over the sciatic nerve, loss of pinprick sensation over the right lateral foot and loss of the Achilles' reflex on the right. In addition, she was found to have a large postvoid urinary bladder residual volume. MRI revealed a 20 mm x 11 mm nonenhancing, heterogenous mass obliterating the spinal canal at the L4 level. At operation, this lesion was found to be adherent to the nerve roots and was completely resected. Pathology revealed this lesion to be a cavernous angioma of the cauda equina. A review of the pertinent literature is presented. CONCLUSIONS: Cavernous hemangiomas of the cauda equina are extremely rare lesions that may present as low back pain, neurologic deficit, or as subarachnoid hemorrhage. They can be successfully treated with surgical excision.

Antioxidant inhibitors for cancer therapy.

Built-in cellular defense mechanisms play a major role in a tumor's protection against non-surgical antineoplastic therapies. Of these, the overexpression of antioxidants such as superoxide dismutase (SOD) may be the most important. Oxygen radicals are highly toxic, and have been implicated in various diseases, including carcinogenesis and aging. They produce a variety of pathological changes through lipid peroxidation and DNA damage. Therefore, treating free-radical-induced diseases with antioxidants has been an accepted therapeutic approach. Ironically, however, the underlying mechanism that most chemotherapeutic agents and ionizing radiation exert on tumor cell kill is not increased antioxidation but rather the production of more free radicals leading to irreversible tissue injury. A small increase in reactive oxygen species (ROS) following non-surgical antineoplastic therapies induces the expression of antioxidants such as SOD, but overproduction of ROS, conversely, exhausts the production of SOD and other adaptive antioxidant defenses. Based on these considerations, we hypothesize that the appropriate administration of antioxidant inhibitors and/or free-radical-generating compounds may be a useful strategy in the treatment of solid tumors.

Pathological correlates of pituitary adenomas presenting with apoplexy.

Pituitary adenomas presenting de novo with apoplectic symptoms are uncommon. Several series on pituitary adenomas with apoplexy have been reported but have emphasized clinical aspects, incidence, or radiographic appearance by computed tomography (CT) scan. We reviewed our 13 years' experience, focusing on pathological appearance. We identified 15 patients with pituitary adenomas whose first presentation to our institution was with apoplexy. By combining histological and intraoperative findings with more sensitive magnetic resonance imaging (MRI) scans, we were able to attribute 5 of 15 cases to bland infarction, five cases to hemorrhagic infarction, four cases to pure clot, and one to a remote hemorrhagic infarction leaving extensive residual fibrosis and hemosiderin. Despite extensive tumor necrosis, reticulin staining still allowed identification of specimens as adenomas. Immunohistochemical staining was informative in 13 of 15 cases and endocrine-inactive, weak gonadotroph and null cell adenomas predominated. Cases with the greatest interval between symptom onset and surgery showed peripheral rim enhancement by MRI. Pathologically, this corresponded to granulation tissue, T cell lymphocytic infiltration, and atrophic pituicytes at the edge of the infarction or hemorrhage. Occasionally this reaction overshadowed the necrotic adenoma and contributed to diagnostic confusion. Our finding of lymphocytic inflammation in pituitary adenomas that have undergone an apoplectic event may suggest at least a modest immune-mediated response to damaged anterior pituitary tissue.

Intralesionally implanted cisplatin plus systemic carmustine for the treatment of brain tumor in rats.

BACKGROUND AND OBJECTIVES: The benefit of conventional chemotherapy for the treatment of malignant brain tumors, although limited, is real. A major obstacle in the treatment of these lesions is the ability to deliver drug across the blood-brain barrier (BBB). Local drug implantation, circumventing the BBB, has been a useful strategy for treatment of intracranial lesions, and may work synergistically with systemic chemotherapy. To test this hypothesis, either intraperitoneal (i.p.) carmustine or cisplatin was combined with the intracranial (i.c.) administration of polymer-delivered cisplatin in rats with intracranial tumors. METHODS AND RESULTS: 9L gliosarcoma tumor cells (5 x 10(3)) were administered through a right frontal lobe cannula in rats 7 days prior to treatments. Cisplatin-loaded biodegradable polymer was then administered via the cannula, with free cisplatin or carmustine injected i.p. Animals were monitored for 60 days post-treatment. In experiment 1, i.c. cisplatin at a dose of 0.5, 1.0, 2.0, and 4.0 mg/m2 resulted in a mean survival time of 34 +/- 3, 39 +/- 14, 47 +/- 11, and 31 +/- 20 days (MST +/- SD), respectively, compared to 26 +/- 4 days in the control group and 30 +/- 7 days in the group treated with 50 mg/m2 i.p. free cisplatin. In experiment 2, i.p. free cisplatin at 25, 40, 50, and 100 mg/m2 resulted in a MST of 28 +/- 3, 30 +/- 4, 32 +/- 3, and 14 +/- 8 days, respectively, compared to 26 +/- 1 days in the control group. In experiment 3, the MST in the groups treated with 0.5 mg/m2 of i.c. cisplatin, 25 mg/m2 of i.p. cisplatin, 10 mg/kg of i.p. carmustine, i.c. cisplatin (0.5 mg/m2) plus i.p. cisplatin (25 mg/m2), and i.c. cisplatin (0.5 mg/m2) plus i.p. carmustine (10 mg/kg) was 30 +/- 4 days (P > 0.05), 28 +/- 2 (P > 0.05), 36 +/- 4 (P < 0.01), 32 +/- 3 (P < 0.01), and 50 +/- 11 days (P < 0.01), respectively, compared to the tumor control group (26 +/- 1 days). Long-term survivors (29%) were seen only in the i.c. cisplatin plus i.p. carmustine group. Additive toxicity was not observed. CONCLUSIONS: Intralesional polymer-delivered (i.c.) cisplatin plus systemic (i.p.) carmustine is highly effective for the treatment of intracranial 9L gliosarcoma in tumors.

Integral and shell-MIP display algorithms in MR and CT three-dimensional models of the brain surface.

BACKGROUND AND PURPOSE: Our purpose was to demonstrate the use of integral and shell maximum intensity projection (shell-MIP) display algorithms in the 3-D CT and MR depiction of cerebral gyral and surface venous anatomy and disorders. These new algorithms are compared against MIP and shaded-surface-display (SSD) algorithms. METHODS: Integral and shell-MIP displays were generated from a specified number of proximal surface voxel layers in a 3-D model. Algorithmic models were compared on nine contrast-enhanced spoiled gradient-recalled acquisition in a steady state (SPGR) MR venograms for brain surface anatomic identification and detail. Seven CT venograms were compared for conspicuity of filling defects. Twelve contrast-enhanced preoperative planning 3-D MR models were rated for neurosurgical utility. RESULTS: A shell-MIP score of 7.00 and an integral score of 6.78 represented the highest mean subjective MR gyral quality (1-10 scale) followed by an SSD score of 3.89 and an MIP score of 1.06. Mean confidence scores for MR central sulcus identification (1-10 scale) were shell-MIP, 7.67; integral, 7.00; SSD, 3.22; and MIP, 1.00. Mean superficial venous quality MR ratings (1-10 scale) were shell-MIP, 8.22; MIP, 7.39; integral, 7.00; and SSD, 3.72. The mean number of cortical veins draining into each side of the superior sagittal sinus on MR was as follows: MIP, 6.19; integral, 6.06; shell-MIP, 5.94; and SSD, 3.81. Mean confidence scores for filling defect identification on CT venograms (1-5 scale) revealed a shell-MIP score of 4.36 and an integral score of 4.29 to be superior to a MIP score of 3.00. In selected cases, 3-D presurgical planning, prior to tumor resection, was clinically useful. CONCLUSION: Integral and shell-MIP are useful 3-D display algorithms for simultaneous display of superficial cerebral veins and gyri on MR images and of thrombosis on CT venograms.

Transdural spinal cord herniation: imaging and clinical spectra.

PURPOSE: Transdural herniation of the spinal cord is a rarely reported clinical entity, and many of the existing reports were published before the advent of MR imaging. We describe five current cases and compare them with findings in 25 cases reported in the literature to delineate the clinical and imaging spectra of transdural spinal cord herniation. METHODS: MR imaging, CT myelography, and conventional myelography were performed in five patients with transdural herniation of the spinal cord. These studies, along with clinical findings, are described. Intraoperative photographs are included for one case. The salient features of both the current and previously reported cases are summarized in tabular form. RESULTS: In three cases, transdural spinal cord herniation occurred posttraumatically, in one case the cause was iatrogenic and in the others the herniation occurred spontaneously. Imaging features not previously reported include dorsally directed herniations at thoracolumbar levels (two patients), apparent (lacking surgical confirmation) syringomeyelia (one case), a vertebral body nuclear trail sign (one case), and intramedullary hyperintensities on MR images (two cases). Clinical features not previously reported include unilateral pyramidal-sensory deficits (one case) and isolated unilateral pyramidal signs (one case). Clinical findings similar to previous reports include progressive paraparesis (two cases) and progressive Brown-Séquard syndrome (one case). CONCLUSION: Our five cases illustrate certain clinical and imaging findings not previously reported, and, together with the established features of the 25 cases in the literature, delineate the spectra of transdural spinal cord herniation.

Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas.

OBJECTIVE: This prospective clinical trial was undertaken to assess the rate of tumor recurrence in patients with endocrine-inactive pituitary macroadenomas who underwent gross total surgical resection of their tumors and did not receive adjuvant radiotherapy. METHODS: Between December 1987 and July 1994, 45 patients with endocrine-inactive pituitary macroadenomas underwent transsphenoidal surgery. In 38 (84%) of these patients, gross total surgical resection was achieved and was confirmed by postoperative magnetic resonance imaging (n = 37) or computed tomography (n = 1). After receiving counseling from the neurosurgeon concerning the risks and benefits of radiation therapy, 32 of the 38 patients elected not to receive adjuvant radiotherapy. Patients were followed through March 1998 with radiographic imaging obtained every 6 months for the first 2 years, annually for postoperative Years 3 and 4, and then every 2 to 3 years thereafter. The study end point was defined as radiographic tumor recurrence or patient death. RESULTS: The mean follow-up duration for the study group was 5.5 years. During that time, 2 of 32 (6%) patients developed recurrence, at 18 and 24 months, respectively, after initial surgery. Both were successfully treated using radiation therapy, with one requiring additional surgery. Three additional patients died as a result of unrelated causes 9, 12, and 49 months, respectively, after initial surgery. Immunocytochemical analysis revealed 66% of the tumors to be weak gonadotroph cell adenomas, 22% to be null cell adenomas, 9% to be silent prolactinomas, and 3% to be silent corticotroph cell adenomas. CONCLUSION: This study demonstrates a 6% 5-year recurrence rate in patients with endocrine-inactive pituitary macroadenomas treated using gross total surgical resection alone. Reserving radiation therapy for the infrequent patient with recurrence and sparing the majority of patients the associated risks inherent in its use seems reasonable.

Telomerase expression shows differences across multiple regions of oligodendroglioma versus high grade astrocytomas but shows correlation with Mib-1 labelling.

AIMS/BACKGROUND: Telomerase is an enzyme that is expressed in most human neoplasms and is associated with tumour immortality. Determination of the point in neoplastic transformation at which telomerase is expressed may aid the understanding of tumour pathogenesis and progression. Despite numerous reports on telomerase, few studies have investigated its expression in high grade glial tumours. These studies, performed on archival banked, single brain tumour specimens, have shown conflicting results for oligodendrogliomas and unexpectedly negative results for telomerase expression in high grade astrocytomas, with one third to one half of glioblastoma multiformes being negative. METHODS: 34 rapidly banked glioma specimens taken from patients undergoing gross total surgical resection of their tumours were studied. Telomerase expression was assessed across 3-8 sampled regions from each tumour by the telomeric repeat amplification protocol (TRAP) assay. Matched mirror image tissue samples were taken for histological analysis of tissue adequacy, statistical correlation of telomerase with tumour histological features, Mib-1 (a marker for cell cycling) labelling, and p53 immunohistochemistry. RESULTS: All five well differentiated oligodendrogliomas were homogeneously telomerase negative and two of three untreated anaplastic oligodendrogliomas were homogeneously positive. In contrast, 10 of 14 high grade astrocytomas showed heterogeneity for telomerase expression across the multiple regions sampled. All glioblastoma multiformes and two of three anaplastic astrocytomas showed at least one region positive for telomerase. When test samples were individually assessed in both oligodendrogliomas and high grade astrocytomas, telomerase expression was associated with Mib-1 labelling (p < 0.001). For the entire group, telomerase expression was associated with grade of tumour, age of patient, and vascular endothelial proliferation (all p < 0.001). CONCLUSIONS: This regional study clarifies that all glioblastoma multiformes are at least focally positive and that telomerase expression correlates with tumour grade in oligodendrogliomas. Homogeneity versus heterogeneity for telomerase expression across multiple regions of oligodendrogliomas versus high grade astrocytomas may provide important preclinical data on the use of antitelomerase agents in these adult glial tumours.