Tumor-associated Cysts Research Articles

NCMP-07. HEADACHE PRESENTATION AND MANAGEMENT IN VON HIPPEL-LINDAU (VHL)-ASSOCIATED HEMANGIOBLASTOMAS

Abstract BACKGROUND Hemangioblastomas are the most common brain tumors among patients with Von Hippel-Lindau (VHL) disease. Common characteristics of these benign tumors, such as tumor growth, peritumoral edema, and cystic expansion, may lead to neurologic morbidity and/or mortality. Thus, early diagnosis based on symptom presentation and appropriate treatment is paramount to VHL-associated hemangioblastoma management. METHODS We conducted a systematic review of PubMed, Scopus, Cochrane, Embase, and Web of Science databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting pre-diagnostic symptoms and post-diagnostic treatments among patients with VHL-associated hemangioblastomas. RESULTS Data from 150 patients were analyzed. The average age at presentation was 35.3 years (range: 18-75) and 52.7% of patients were female. Headache was the most common presenting symptom (73.3%). Other presenting symptoms included balance or gait disturbances (42%), ataxia (41.3%), nausea (24.3%), emesis (24.3%), dysmetria (15.5%), swallowing difficulties (11.3%), and singultus (10.7%). Anatomically, 98.7% of tumors were in the posterior fossa, specifically 69% in the cerebellum and 30% in the brainstem. Approximately 62.8% of patients had tumor associated cysts. A majority of the patients (98.7%) underwent gross-total resection of the tumor and cyst drainage as needed. Other common treatments included radiotherapy, gamma-knife surgery, and ventriculoperitoneal shunt placement. CONCLUSION Patients with VHL-associated hemangioblastomas commonly presented with headaches, balance or gait difficulties, and ataxia. Tumors were generally found in the posterior fossa and were associated with cysts. Gross-total resection was the main treatment offered to patients with these tumors.

Reconciling the Biological and Transcriptional Variability of Hepatoblastoma with Its Mutational Uniformity.

Simple SummaryHepatoblastoma (HB), the most common form of childhood liver cancer, is associated with dual mutation and/or dysregulation of the Wnt/β-catenin and Hippo pathways in ~50% of cases. However, this mutational simplicity cannot explain HB’s biological and histologic diversity. This discussion focuses upon recent work showing that specific β-catenin mutants are key determinants of this HB variability as well as their metabolic and transcriptional signatures. Dysregulation of the anti-oxidant NFE2L2 pathway also contributes to tumorigenesis by being directly transforming in association with either of the other two factors. The transcriptional overlap of tumors generated by pairs of factors identifies crucial targets that likely mediate HB tumorigenesis, behavior and appearance.Hepatoblastoma (HB), the most common childhood liver cancer, is associated with seven distinct histologic subtypes and variable degrees of clinical aggressiveness and presentation. Yet it is among the least genomically altered tumors known, with about half of HBs showing mutation and/or dysregulation of the Wnt/β-catenin and Hippo pathways. This raises the question of how this mutational simplicity can generate such biological and histologic complexity. Recent work shows that the identity of the underlying β-catenin mutation is a major contributor. Mutation or over-expression of the NFE2L2/NRF2 transcription factor, previously thought only to promote anti-oxidant responses, has also recently been shown to accelerate the growth of HBs generated by mutations in the Wnt/β-catenin and Hippo pathways while imparting novel features such as the tumor-associated cysts and necrosis. Moreover, patient-associated NFE2L2 mutations are overtly transforming when co-expressed with either mutant β-catenin or a Hippo pathway effector. The finding that tumorigenesis can be driven by any two arms of the β-catenin/Hippo/NFE2L2 axis has permitted the identification of a small subset of coordinately regulated tumor-specific transcripts, some of whose levels correlate with inferior long-term outcomes in HB and other cancers. Collectively, these findings begin to provide for more refined and molecularly based classification, survival algorithms and design of chemotherapeutic regimens.

Surgical management of periventricular glioma: decision-making and preoperative assessment of resectability

Objective. Periventricular gliomas (PVG) are deep-seated tumors with wide invasion into cerebral core structures accompanied by high rates of postoperative deterioration and early relapse. The purpose of this study was to define the preoperative neuroimaging signs as the factors determining the early postoperative outcome in patients with high-grade PVG. Materials and methods. The clinical records of 132 (50 females and 82 males) consecutive patients with a mean age 45.9 years (range 21–69) undergoing image-guided surgery for PVG at a single academic institution were retrospectively analyzed. There were 52 (39.4 %) WHO grade III gliomas, and 80 (60.6 %) of patients had WHO grade IV gliomas. Results. Postoperative median KPS score significantly raised from 67.4 to 82.0, as well as a number of patients with the KPS score ≥ 70: from 18 (13.6 %) to 109 (82.6 %) with p<0.01. The multivariate regression analysis revealed that poor postoperative functional status was associated with basal ganglia involvement (OR 2.75, 95% CI 0.93–8.09, p = 0.07), the higher EOR grade (OR 3.30, 95% CI 1.15–9.43, p = 0.03), and hydrocephalus (OR 5.08, 95% CI 1.49–17.35, p = 0.09). Total/subtotal resection was carried out in 84 (63.6 %) cases; in 48 (36.4 %) cases, the partial resection was performed. The multivariate logistic regression analysis revealed that three factors decreased the likelihood of total/subtotal resection in PVG: basal ganglia invasion (OR 0.18, 95% CI 0.06–0.55, p< 0.01), minor extraventricular part (OR 0.40, 95% CI 0.17–0.94, p = 0.04), and contralateral side extension (OR 0.38, 95% CI 0.16–0.92, p = 0.03). In contrast, the presence of tumor-associated cyst (OR 3,73, 95% CI 1.32–10.54, p = 0.01) increased odds of total/subtotal resection. The four-tear grading system of PVG integrating statistically identified factors of total/subtotal resection and risks of postoperative neurological deterioration was developed. The Kaplan-Meier analysis showed that overall median survival was 17.7 ± 1.9 months for patients with high-grade PVG. The survival analysis using Cox regression model revealed that age over 45 years (HR 1.77, 95% CI 1.06–2.99; p = 0.03) and higher tumor WHO grade (HR 2.24, 95% CI 1.27–3.95; p = 0.005) significantly decreased survival rates. Conclusions. The proposed grading system provides the possibility of preoperative evaluation of PVG resectability that in combination with 3D surgical planning and image-guided resection allows performing maximal safe resections and preventing of postoperative neurological deficits.

Resection of a cerebellar hemangioblastoma via a minimally invasive tubular approach

Hemangioblastomas are rare benign, highly vascularized tumors occurring in the cerebellum and the spinal cord. They often develop tumor-associated cysts multiple times the size of the solid part of the tumor. Patients with von Hippel-Lindau (VHL) disease typically exhibit multiple tumors with the need of repeated surgeries during their lifetime. As multiple surgeries involve an increased risk of access-related morbidity, a minimally invasive approach can be favorable for specific types of tumors in the posterior fossa. We here present the case of a minimally invasive removal of a superficial cerebellar hemangioblastoma with tumor-associated cyst and indicate the potential benefits and limitations of this technique.

Spinal cysts : Diagnostic workup and therapy

Spinal cysts can be classified as meningeal, not meningeal, and tumor-associated cysts. Due to the widespread availability of high-resolution computed tomography and magnet resonance imaging, spinal cysts can be detected with high sensitivity these days. Concerning the variety of potential cystic differential diagnoses, aprecise classification is difficult and can often only be realized after surgical inspection or histological examination. Spinal cysts are generally incidental findings during a routine diagnostic workup and need no further therapy. Surgical treatment can be necessary if the spinal cyst reaches acertain size and causes neurological symptoms due to the compression of the spinal cord or the nerve root.

Pediatric central nervous system hemangioblastomas: different from adult forms? A retrospective series of 25 cases.

Pediatric hemangioblastomas are rare, and the clinical features, timing of surgical intervention, optimal treatment, and clinical outcomes are still unclear. We performed a retrospective study of all patients with CNS hemangioblastomas who were treated at West China Hospital from January 2003 to March 2015. Patients under the age of 16years were included in the study. The medical records of these patients were reviewed and statistically analyzed. Twenty-five children (15 females and ten males, [mean age 12.6±4.7years, range 1-16years]) presented with hemangioblastomas. Tumors were detected in the cerebellum, brainstem, and spinal cord in 40, 28, and 32% of patients, respectively. Sixteen children (64%) had VHL syndrome. The most frequent symptoms were those related to increased intracranial pressure. The mean duration of symptoms was 1.5±2.1months. Preoperative hydrocephalus was noted in 11 children (44%). Gross total resection was achieved in all children. Clinical symptoms improved in 19 children (76%), unchanged in four children (16%), and aggravated in two children (8%), respectively. The mean follow-up was 44.5±32.3months. Five patients (20%) experienced disease progression. Using univariate analysis, both tumor-associated cysts (P=0.027) and VHL disease (P=0.032) were significantly related to postoperative outcomes. Pediatric hemangioblastomas have many different clinical features compared with adult cases. A high degree of suspicion for VHL disease should be raised in pediatric hemangioblastomas. Despite many challenges involved, surgical outcomes for pediatric hemangioblastomas are favorable. Lifelong follow-up is mandatory to detect the disease progression.

Surgical treatment of cerebellar hemangioblastomas.

Background:Hemangioblastomas (HBL) are uncommon tumors of the central nervous system (CNS), corresponding to 1–2.5% of all intracranial tumors. They can present sporadically or in patients with von Hippel–Lindau (VHL) disease and are most often located in the cerebellum, brainstem, and spinal cord. VHL disease is a multiple neoplasia syndrome inherited in an autosomal dominant fashion and caused by a VHL suppressor gene deletion. We present our experience in the management of patients with cerebellar HBL.Methods:Thirty consecutive patients with cerebellar HBL were included in this study. Hospital charts, radiological images, and operative records were reviewed. Modified Rankin scores were used to evaluate the clinical course.Results:Thirty patients diagnosed with cerebellar HBL were operated. Complete total resection was achieved in 93% of the cases. Postoperatively, 83% of the patients showed good functional recovery.Conclusions:HBL of the cerebellum should be resected when symptomatic or when the tumor (or a tumor-associated cyst) shows signs of enlargement. Surgical intent should seek en bloc resection to minimize intraoperative bleeding. Patients with HBLs must be tested for VHL gene mutations, and in confirmed cases, relatives should be offered genetic counseling.

P.2.c.010 Duloxetine for pathological laughing and crying in amyotrophic lateral sclerosis

Patients with pathological laughter and crying have episodes of uncontrollable laughter, crying or both. Pathological laughter is a well-described entity secondary to various conditions such as multiple sclerosis, pseudo-bulbar palsy, cerebello-pontine angle tumours, clival chordomas and brainstem gliomas. Pathological crying is rare and there have been no previous reports of brainstem compression causing this entity. We report a patient who presented with pathological crying caused by a trigeminal schwannoma with a tumor-associated cyst indenting the pons. This case report confirms the involvement of the cortico-ponto-cerebellar pathways in the pathogenesis of pathological crying.

Brainstem compression from a trigeminal schwannoma presenting with pathological crying

Patients with pathological laughter and crying have episodes of uncontrollable laughter, crying or both. Pathological laughter is a well-described entity secondary to various conditions such as multiple sclerosis, pseudo-bulbar palsy, cerebello-pontine angle tumours, clival chordomas and brainstem gliomas. Pathological crying is rare and there have been no previous reports of brainstem compression causing this entity. We report a patient who presented with pathological crying caused by a trigeminal schwannoma with a tumor-associated cyst indenting the pons. This case report confirms the involvement of the cortico-ponto-cerebellar pathways in the pathogenesis of pathological crying.

Increased expression of intracystic matrix metalloproteinases in brain tumors: relationship to the pathogenesis of brain tumor-associated cysts and peritumoral edema

Although several types of brain tumors are commonly associated with cyst formation, the pathogenesis of tumor-associated cysts (TAC) is unknown. We investigated the matrix metalloproteinase (MMP) expression of cyst fluids to elucidate the pathogenesis of TAC in brain tumors. We also examined the relationship between the severity of peritumoral edema and the expression of intracystic MMP. We collected 40 cyst fluid samples from 34 patients with TAC and studied the expression of MMP-2 and -9 in the cyst fluid using gelatin zymography. Radiological studies were used to estimate the severity of the peritumoral edema and to determine the presence of TAC. Although gelatin zymography of the cyst fluid showed high levels of MMPs, there was no correlation between the expression of MMPs in the cyst fluid and that in the tumor tissue. The level of MMP expression in the cyst fluid did not reflect the pathologic grade of the individual tumors. However, the total and activated MMP-9 levels were significantly associated with the severity of the peritumoral edema ( p < 0.05). These results suggest that MMPs may be partly involved in the pathogenesis of TAC and peritumoral edema in brain tumors.

Neurofiberscopic Biopsy of Tumors of the Pineal Region and Posterior Third Ventricle: Indications, Technique, Complications, and Results

Evaluation of results of the neurofiberscopic biopsy of tumors of the pineal region and posterior third ventricle. From 2001 to 2004, 23 patients (mean age, 30.6 yr) with tumors located in the pineal region or posterior third ventricle underwent neurofiberscopic biopsy with simultaneous third ventriculostomy. The procedure was indicated for verification of the histological diagnosis of the neoplasm, which was planned to be treated by radiotherapy and/or chemotherapy without open surgery (eight patients), establishment of the pathological diagnosis for further choice of the most appropriate treatment strategy (11 patients), differentiation of the recurrent neoplasm and radiation necrosis (two patients), and decompression of the large tumor-associated cyst (two patients). In six previously shunted patients, substitution of the ventriculoperitoneal shunt on the third ventricle stoma was performed. There was no postoperative mortality or permanent morbidity. In all cases, the obtained tissue sample was sufficient for pathological diagnosis. Transient postoperative complications included fever (15 patients), nausea and vomiting (three patients), and diplopia (one patient). On the long-term follow-up, delayed third ventricular stoma failure caused by tumor regrowth and scar formation was found in one patient, and dissemination of the malignant glioma through the subarachnoid space was found in another patient. Neurofiberscopic biopsy represents a useful method for sampling of tumors of the pineal region and posterior third ventricle, which can be effectively used in both previously shunted and shunt-free patients.

The long-term results of gamma knife radiosurgery for hemangioblastomas of the brain

The authors assessed the long-term result of gamma knife surgery (GKS) for hemangioblastomas of the brain (HABs) and show histopathological findings after GKS. Thirty-five patients, 28 men and seven women, with a mean age of 36 years underwent GKS. Eighteen patients presented with multiple tumors and 17 with a solitary tumor. Twenty-one patients had von Hippel-Lindau (VHL) disease. The mean tumor diameter was 13 mm (range 5-55 mm). The mean follow up after GKS was 66 months (range 24-114 months). The mean prescription dose was 17.2 Gy (range 12-24 Gy) at the tumor margin. For tumors close to or within the brainstem a prescription dose of 12 to 13 Gy was used. At the most recent follow up, 29 patients were alive, six were dead, and satisfactory tumor control had been achieved in 29. A stable or improved neurological status was obtained in 21 patients. Eight patients underwent open surgery because of tumor-associated cyst enlargement or the development of new tumors after GKS. Seven patients developed new tumors and five of them required a second GKS. The 1-year tumor control rate was 94%; 2 years, 85%; 3 years, 82%; 4 years, 79%; and 5 years, 71%. Histopathology showed that no tumor cells were found and there was degeneration and necrosis in a tumor nodule 48 months after GKS with a prescription dose of 18 Gy. Gamma knife surgery was a useful choice for small- or medium-sized, solid HAB in the long term, especially when the tumor margin dose was 18 Gy. Although GKS can treat multiple tumors in a single session, for HABs associated with VHL disease, GKS faces the dual problems of tumor recurrence or development of a new tumor.

The long-term results of gamma knife radiosurgery for hemangioblastomas of the brain

Object. The authors assessed the long-term result of gamma knife surgery (GKS) for hemangioblastomas of the brain (HABs) and show histopathological findings after GKS. Methods. Thirty-five patients, 28 men and seven women, with a mean age of 36 years underwent GKS. Eighteen patients presented with multiple tumors and 17 with a solitary tumor. Twenty-one patients had von Hippel—Lindau (VHL) disease. The mean tumor diameter was 13 mm (range 5–55 mm). The mean follow up after GKS was 66 months (range 24–114 months). The mean prescription dose was 17.2 Gy (range 12–24 Gy) at the tumor margin. For tumors close to or within the brainstem a prescription dose of 12 to 13 Gy was used. At the most recent follow up, 29 patients were alive, six were dead, and satisfactory tumor control had been achieved in 29. A stable or improved neurological status was obtained in 21 patients. Eight patients underwent open surgery because of tumor-associated cyst enlargement or the development of new tumors after GKS. Seven patients developed new tumors and five of them required a second GKS. The 1-year tumor control rate was 94%; 2 years, 85%; 3 years, 82%; 4 years, 79%; and 5 years, 71%. Histopathology showed that no tumor cells were found and there was degeneration and necrosis in a tumor nodule 48 months after GKS with a prescription dose of 18 Gy. Conclusions. Gamma knife surgery was a useful choice for small- or medium-sized, solid HAB in the long term, especially when the tumor margin dose was 18 Gy. Although GKS can treat multiple tumors in a single session, for HABs associated with VHL disease, GKS faces the dual problems of tumor recurrence or development of a new tumor.

Phase II trial of the EGFR tyrosine kinase inhibitor erlotinib for single agent therapy of recurrent Glioblastoma Multiforme: Interim results

1558 Background: Erlotinib (Tarceva, OSI-774) is an orally available small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. We have initiated the first phase II trial of erlotinib in single agent therapy of recurrent glioblastoma multiforme (GBM). Methods: Patients with documented recurrent or progressive GBM who have received previous radiation therapy and cytotoxic chemotherapy were eligible for enrollment. No enzyme-inducing anti-epileptic agents were allowed. Patients were treated with 150 mg of erlotinib per day until tumor progression or study withdrawal. Tumor response was determined by MRI. Analysis for EGFR amplification was performed. Results: Interim analysis has been performed on a total of 16 of 31 planned patients as of December, 2003. Of these, 4 patients have shown partial responses, 1 showed a partial response of his original tumor but then developed a separate unresponsive focus and 4 have had disease stabilization for greater than 3 months. Seven patients have had tumor progression within 3 months of starting erlotinib. Although a response has been seen in 50% of patients (4 PR + 4 SD), the responses have not been durable; the median time to progression of responders has been 145 days after the start of therapy. Eleven patients have died since the start of the study. The pattern of subsequent treatment failure in responders has suggested a diffuse spread of tumor (e.g. gliomatosis cerebri or leptomeningeal spread). One patient had a tumor-associated cyst in which the steady state OSI-774 level was determined and found to be approximately 40% of that observed in plasma. Approximately one-half of the tumors have had EGFR amplification, but EGFR amplification has not ensured a response to erlotinib and responses have been observed in the absence of amplification. Conclusions: Although these results are preliminary in nature, we are encouraged by the response rate observed to date. The apparent lack of durability of response and the pattern of post-response failure may be due, in part, to reduced drug penetration into the brain, an inadequate dose and/or tumor heterogeneity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech

The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease.

The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel-Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment. The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia. The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts. In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect-producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment.

Second Surgery for Recurrent Pilocytic Astrocytoma in Children

Pilocytic astrocytoma (PA) is the most common childhood brain tumor. In cases where the tumor progresses or recurs following primary surgical resection, the appropriate treatment is unclear. Options include chemotherapy, radiation therapy, surgical resection or a combination thereof. To analyze the utility of further surgery, we performed a retrospective, single-institution review of pediatric patients with recurrent PAs from 1990 to 1999 who were treated with a second surgical resection. Patients were excluded if they received adjuvant chemotherapy or radiation therapy. Twenty cases were identified. Tumor locations included: cerebral hemisphere (3), cerebellum (7), optic pathway/hypothalamus (5), thalamus (1) and brainstem (4). The indication for 4 surgeries included an enlarging tumor-associated cyst. At second surgery, 10 of 20 patients had a gross total resection (GTR), 2 a near total resection (NTR), and the remaining 8 patients had a subtotal resection (STR). No patients have died. Two of 10 tumors after GTR, 0 of 2 tumors after NTR, and 7 of 8 tumors after STR had second recurrence/progression at a mean of 15 months (range 4–33 months) following second surgery. The remaining 11 patients are recurrence/progression-free at a mean of 40.7 months (range 19–119 months). Surgery for tumors or midline structures rarely resulted in a GTR (1 of 10 cases). Surgery for tumors located in the cerebral hemispheres or cerebellum resulted in GTR or NTR in all cases and can result in long periods of progression-free survival without further adjuvant treatment.

Expression of vascular permeability factor in craniopharyngioma.

The expression of vascular endothelial growth/permeability factor (VEG/PF) has recently been correlated with the presence of tumor-associated cysts in some intracranial tumors. The purpose of this study was to evaluate a possible relationship between the presence of VEG/PF and the formation of cysts in craniopharyngiomas. The expression of VEG/PF was studied in histological specimens from a series of 12 craniopharyngiomas. In this series, the tumors were classified as presenting a mainly solid pattern with small macroscopic cysts (four patients) or a mainly cystic pattern (eight patients). The mainly solid tumors containing small macroscopic cysts showed little or no VEG/PF positivity, which was mainly present in tumor cells surrounding cysts. Nevertheless, mainly cystic craniopharyngiomas showed a moderate or high degree of VEG/PF positivity in tumor cells. These findings indicate that the predominance of a cystic or solid macroscopic appearance of craniopharyngiomas may be influenced by the degree of VEG/PF expression within the tumor cells.

Vascular permeability factor expression in cerebellar hemangioblastomas: correlation with tumor-associated cysts.

The presence of vascular endothelial growth/permeability factor (VEG/PF) has been studied in histological specimens from a series of 16 cerebellar hemangioblastomas. In this series, the tumors were classified as presenting a macroscopic solid pattern (4 cases), a mainly solid pattern with macroscopic cysts (4 cases) or a mainly cystic pattern (8 cases). Solid tumors showed a low degree (75% of cases) or moderate degree (25% of cases) of VEG/PF positivity. The mainly solid tumors containing macroscopic cysts showed a moderate degree (50% of cases) or high degree (50% of cases) of VEG/PF positivity. Nevertheless, mainly cystic hemangioblastomas showed a high degree (87.5% of cases) or moderate degree (12.5% of cases) of VEG/PF positivity. These findings suggest that the predominance of a cystic or solid macroscopic appearance of cerebellar hemangioblastomas may be influenced by the degree of VEG/PF expression within the tumor tissue.

Vascular endothelial growth/permeability factor expression in human glioma specimens: correlation with vasogenic brain edema and tumor-associated cysts

Peritumoral vasogenic brain edema (PVBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma fluid and proteins through the interendothelial spaces. Tumor-associated cysts (TACs) are observed more commonly with benign gliomas that are not associated with PVBE. This study investigates the hypothesis that these morphologically distinct epiphenomena of microvascular extravasation are linked by a common pathophysiological mechanism involving vascular endothelial growth/permeability factor (VEG/PF), which has been implicated in vascular leak phenomena including ascites, malignant effusions, and brain edema. Furthermore, VEG/PF has been isolated from cultured glioma cells, and both VEG/PF protein and messenger RNA transcripts are expressed in brain tumor tissue. To further elucidate the relationship of VEG/PF to PVBE and TACs, the authors examined 34 pathological specimens for VEG/PF expression. Nineteen primary low-grade tumors, 11 primary high-grade tumors, and four gliosis controls were immunostained with a polyclonal anti-VEG/PF immunoglobulin G antibody. Magnetic resonance imaging was used to quantitate PVBE and to determine the presence of TACs and tumor enhancement. The study revealed that eight VEG/PF-negative specimens exhibited no significant edema, whereas 26 VEG/PF-positive tumors exhibited either significant PVBE or TACs. Notably, eight of nine benign TACs that were not associated with PVBE immunostained positive for VEG/PF. These data indicate a high degree of correlation between VEG/PF expression by gliomas and the occurrence of PVBE or TACs, irrespective of tumor grade, thus supporting VEG/PF's pivotal role as the common pathophysiological link between these processes.

Spinal cord tumors: gadolinium-DTPA-enhanced MR imaging

To assess the utility of gadolinium-DTPA (Gd) and of MR imaging in the evaluation of spinal cord tumors, ten consecutive patients were prospectively evaluated. T1-proton density-, and T2-weighted images were obtained in sagittal or axial planes. T1-weighted images were obtained before and after intravenous administration. Five tumors were within the cervical spinal cord; 3 neoplasms were within the thoracic cord; 1 neoplasm extended from the cervical to the thoracic cord and 1 neoplasm extended from the cervical cord to the conus medullaris. Four tumors were ependymomas; 3 were astrocytomas; 1 was an hemangioblastoma, and 1 was a metastatic malignant peripheral nerve sheath tumor. The remaining patient died prior to spinal surgery and no autopsy was obtained. Of the precontrast sequences, tumors were best evaluated using T1-weighted images. Abnormal findings included cord widening, presence of a tumor mass, intratumoral or other associated cyst(s), and hemorrhage. Nevertheless, T1-weighted images obtained following the administration of GD were superior relative to all other pre- and post-contrast sequences for defining tumor margins, characterizing cyst(s) and delineating tumor masses. Based primarily on their appearance on post-contrast T1-weighted images, tumor-associated cysts could be subcategorized into 3 types: intratumoral cysts (found within the contrast-enhancing soft tissue mass); nonenhancing extratumoral cysts (found eitherrostral or caudal to the enhancing tumor mass); and enhancing extratumoral cysts (having an enhancing wall or containing an enhancing nodule).(ABSTRACT TRUNCATED AT 250 WORDS)