Partial Tumor Resection Research Articles

Apoplejía tumoral hipofisaria posquirúrgica. A propósito de dos casos

We report two cases of large macroadenomas that, after a transsphenoidal partial resection, suffered necrosis and swelling of the residual tumor, with increase of its volume, compression of neighboring structures and neurological deterioration. The literature is reviewed looking for possible pathophysiological mechanism and prevention.

Analysis of the pyramidal tract in tumor patients using diffusion tensor imaging

In this work, we propose to use fiber tracking in order to analyze and quantify the state of the pyramidal tracts in patients affected by tumors. We introduce a framework that includes an automatic method to obtain the fibers involved in the pyramidal tract of any subject, in order to compare robustly fiber bundles affected by tumors with healthy fiber tracts from control subjects and also to quantify the relative state of degeneration between the fiber tracts in the two hemispheres of the same patient. The comparative analyses proposed in our methodology are based on a new set of measures on the pyramidal tract, which take into account intrinsic properties of the fibers involved in the bundle as well as the similarity with the pyramidal tract of a standard healthy subject, modeled as the average of a set of controls. In order to perform better comparison studies and to take into account more information of the whole bundle, a mapping technique is used to represent the fiber tracts in 2D. Here, we show a set of experiments using 5 tumor patients and 10 control subjects, including pre- and post-operative studies in patients that have been treated with partial or total tumor resection. The results obtained indicate the usefulness of the method showing good overall performance. A reproducibility study using several acquisitions of the same patient is also presented to validate the techniques employed.

Primary Pulmonary Artery Sarcoma: Surgical Management and Differential Diagnosis with Pulmonary Embolism and Pulmonary Valve Stenosis

Primary pulmonary artery sarcomas are rare and lethal tumors that are usually diagnosed during surgery or autopsy. We present six cases of primary pulmonary artery sarcomas and discuss clinical features, differential diagnosis, surgical treatment, and outcome of the tumors. Between January 1994 and July 2008, six patients were identified with the disease during operation. Three patients were initially diagnosed with pulmonary valve stenosis, and two patients had a presumptive diagnosis of chronic pulmonary embolism. Two patients had simple or partial tumor resection. Four patients had radical tumor resection and homograft reconstruction of the pulmonary arteries. Histological examinations showed five malignant mesenchymomas and one fibrosarcoma. One patient died of refractory pulmonary hypertension during operation. Two patients died 4 months postoperatively because of brain metastases. Two patients were alive for 3 and 9 months, respectively after the operation with recurrent tumor. One patient is alive even 2 years after resection with no signs of recurrence or metastasis. Because of similar clinical features, pulmonary artery sarcomas are often confused with other pulmonary vascular obstructive diseases. Computed tomography scanning and gadolinium-enhanced magnetic resonance imaging could be useful methods for differential diagnosis. The prognosis is very poor. The survival time after resection varies from several months to several years depending on the presence of recurrence or metastasis. Early diagnosis and radical surgical resection presents the only opportunity for a potential cure.

Diffusion magnetic resonance imaging early detect the radiotherapy response of glioma

Objective To evaluate the role of diffusion magnetic resonance imaging(MRI) in early detection of the treatment response of radiation for glioma. Method Conventional and diffusion MRI were acquired before and at 3 weeks later after initiating radiotherapy for newly diagnosed glioma patients,who had partial tumor resection. ANOVA was used to compare the diffusion MRI parameters among different treatment response groups. Receiver operating characteristic (ROC) curve was used for judgment of sensitivity and specificity of the parameters. Results There was no statistically significant differences (P>0.05) of the pretreatment apparent diffusion coefficient (ADC), ADC during treatment, ADC subtraction value, pretreatment accumulated ADC value,accumulated ADC value during treatment among partial response (PR) group, stable disease(SD) group and progressive disease (PD) group patients. There was statistical differences (P<0.05) of accumulated ADC change percentage among the groups. The predictive value and overall accuracy for early detection of treatment response by the accumulated ADC change percentage was 92.7%. The sensitivity and specificity for predicting PD patients were 81.9% and 96.2% respectively. Conclusions Diffusion MRI could predict the radiotherapy response of glioma patients. Accumulated ADC change percentage is a good parameter for the early detection of PD patients during the treatment of radiation. Key words: Diffusion magnetic resonance imaging; Glioma; Radiosurgery; Prognosis; Iimaging predictor

Local resection of metanephric adenoma with kidney preservation

Metanephric adenoma (MA) is a rare renal neoplasm present at any age. Usually, a total nephrectomy is performed. Some successful partial nephrectomies or selective tumor resections are described in adults but not in children. We present here the case of a 15-month-old boy, the youngest patient yet to be reported with an MA. We performed a local resection of the tumor. Today, 2 1/2 years after surgery, we can document a favorable clinical course and normal ultrasound findings in the follow-up of the operated kidney. This case gives further evidence that organ-sparing resection of MA is feasible in selected cases. A close clinical and ultrasound follow-up is mandatory for this approach.

Combinative therapy of microsurgery and radiotherapy for intracranial chondrosarcoma

Objective To explore the diagnosis and outcome, after eombinative therapy of microsurgery and radiotherapy for intracranial chondrosarcoma. Method We retrospectively reviewed 8 patients diagnosed as intracranial chondrosarcoma and treated by microsurgery from 2000 to 2007. All of the 8 patients underwent surgical resection of tuners as the initial treatment and the pathological subtypes of tumors were also detected. Their clinical manifestations and outcomes after the treatment of combination of microsurgery and radiotherapy were analyzed in order to evaluate the therapeutic significance. Results According to the histopathological standard,5 cases were of the classical subtypes,2 cases were of mesenchymal subtypes, 1 case was of the myxoid subtype. The total resection and sub-total resection was achieved in 5 and 2 intracranial chondrosarcoma cases, respeetively. Partial tumor resection was obtained in one case. All patients were followed up from about 6 months to 3 yearn. In the 5 cases with total tumor resection,2 cases suffered from tumor recurrence at about the 9th and 12th months after the operation. The 2 cases survived well after taking radiotherapy. One case died at the 24th month after operation because of tumor recurrence at about 18 months without radiotherapy. The left 2 cases survived well because of the preventative radiotherapy after operation. 2 of the 3 cases with partial tumor resection also survived well because of the early radiotherapy after operation. One case lost. Conclusions The outcome of intracranial chondrosarcoma is fine after the combinative therapy of micrnsurgery and radiotherapy although it is malignant. Key words: Chondrosarcoma; Microsurgery; Radiosurgery; Combi-native therapy

Primary Pituitary Lymphoma: A Histological, Immunohistochemical, and Ultrastructural Study with Literature Review

We report the case of a 62-year-old man with headache and left sixth cranial nerve palsy. A computerized tomography scan revealed an osteolytic process involving the sella turcica and clivus. A partial tumor resection was achieved via an endoscopic transsphenoidal approach. Morphologic investigation revealed a diffuse large B cell lymphoma involving pituitary parenchyma. No systemic disease was found upon staging. Primary pituitary lymphoma is extremely rare. An accurate histologic diagnosis is key to successful treatment and a favorable prognosis. The literature is reviewed.

Endoscopic options in children: experience with 134 procedures

There are frequent applications for endoscopy in neurosurgery. However, endoscopic surgery in children has peculiar characteristics and is associated with different rates of success. In this study, the authors report on their experience with 134 consecutive endoscopy procedures performed in 126 patients<18 years of age. Between April 1993 and October 2007, 134 endoscopic procedures were performed in 126 children. Indications for surgery included brain tumors in 48 children, cystic lesions in 24, aqueductal stenosis in 23, various malformations in 20, hemorrhage and infarction in 6, and isolated ventricles in 5 children. In this long-term followup study, data were analyzed with respect to clinical and radiological success rates, as well as shunt dependence both in relation to lesion origin, and to the type of endoscopic procedure performed (endoscopic third ventriculostomy [ETV], septostomy, aqueductoplasty, or cystocisternostomy). Finally, the influence of patient age on the success rate was evaluated. In 114 patients, restoration of CSF circulation was the goal of endoscopy, but in 2 patients only ventriculoscopy was performed followed by ventriculoperitoneal shunt placement. In 12 of 114 patients, tumor biopsy sampling or resection was performed simultaneously with shunt placement. In another 12 patients, only endoscopic tumor resection without CSF circulation restoration was done. The follow-up period ranged from 1 to 6 years. Thirteen tumor biopsies, 7 partial tumor resections, and 4 endoscopically complete tumor resections were performed. An intraoperative switch to microsurgery was made in 2 patients because of recurrent hemorrhage and an overly time-consuming endoscopic surgery. Cerebrospinal fluid circulation was successfully restored in 81 (72%) of 112 patients, with the use of endoscopy in the setting of tumor-related hydrocephalus providing the best results (86% success rate). However, of the various endoscopic procedures, cyst openings (cystocisternostomy, cystoventriculostomy, and ventriculocystocisternostomy) provided the best results-superior even to ETV-with a success rate of 77% and no complications. In contrast, endoscopic aqueductoplasty had a high failure and complication rate. Patients<6 months old who underwent ETV, septostomy, or aqueductoplasty had poor results and became more frequently shunt dependent than older children. Overall, endoscopy can be considered safe and effective in children. Based on the authors' data, acute hydrocephalus cases such as those caused by tumors are the best candidates for endoscopic CSF flow restoration. Interestingly, cyst openings to the ventricles or cisterns were the most successful endoscopic techniques with the lowest complication rate. Aqueductoplasty should be reserved for selected cases. Finally, the success rate of endoscopic techniques remains poor in infants<6 months of age; this was not only true of ETV, but also other techniques such as septostomy and aqueductoplasty.

Indications and Outcome of Endoscopic Papillectomy of the Major and Minor Papilla—a Prospective 5-year Study

Endoscopic papillectomy is a promising and challenging endoscopic intervention. The aim of this study was i) to classify the differential indication, and ii) to study the outcome in papillectomy of suspicious tumor lesions of the papilla of Vater (papilla). Methods Thirty nine patients were enrolled (22 males/17 females; range of age, 21-88 years) who underwent endoscopic papillectomy because of a polypoid tumor at the papilla revealed by previous endoscopic ultrasonography (EUS) over a time period of 5 years. Follow-up EUS and histologic investigation were performed within 28 days(d). Results I) All tumors were detectable using EUS (range of tumor size, 1-4.5 cm). II) Indications, histologic diagnoses and their distribution were as follows: Group(Gr.)1 ( n = 21): Adenoma ( n = 18), uT1 carcinoma(Ca) of high risk patients ( n = 3) with R0 resection ( n = 17) vs. R1 ( n = 4; all reapproached using argon beamer). On the 28th postinterventional d, all subjects were free of tumor. Recurrent tumor growth was found in 3 cases after 6, 18 and 26 months respectively (range of endoscopic follow up [ n = 14], 3-60 months). Three patients (free of tumor) died from other causes after 3, 8 and 18 months, respectively. Gr. 2 ( n = 8): Contradiction between EUS (infiltrating tumor growth) and histologic finding (adenoma or unspecific inflammation); histological findings were: Adenomyomatosis of the papilla ( n = 5), infiltrating Ca of the papilla or peripapillary region ( n = 3). Gr. 3 ( n = 4): Neuroendocrine tumors of the major ( n = 2) or minor papilla ( n = 2): 2 benign, 1 Ca and 1 carcinoid tumor. Gr. 4 ( n = 6): Non-introducible catheter through the minor papilla in case of suspected pancreas divisum ( n = 2) or through the major papilla ( n = 1) after previous gastric resection (Billroth II) or because of Ca of the papilla with no successful attempts to drain the bile duct ( n = 3): Catheter insertion was achieved after papillectomy ( n = 3) or partial tumor resection ( n = 3). III) Complications: 8 of 39 patients (20.5%) developed postinterventional pancreatitis (severe course, n = 1); in 7 cases, bleeding occurred, no perforation was seen. The rate of recurrent tumor growth after R0 resection was 17.6% (3 of 17 subjects). In papillectomy is feasible in the case of i) polypoid tumor of the papilla, ii) infiltrating tumor growth revealed by EUS and negative histologic investigation (optional: plus deep biopsy), and iii) tumor lesion, through which catheter can not be placed to get access to the pancreatobiliary system. In endoscopic papillectomy fulfills diagnostic as well as therapeutic requirements and can be recommended as minimally invasive but appropriate method for well-defined indications of papillary tumor lesions.

Minimally Invasive Surgery for Skull Base Tumors

The Jefferson Center for Minimally Invasive Cranial Base Surgery and Endoscopic Neurosurgery reflects three of the current evolutions in neurological surgery. The first of these is reflected in the name of the Center itself. Surgical Procedures, Minimally Invasive, a Medline Subject Heading since 1998, is defined as: Procedures that avoid use of open invasive surgery in favor of closed or local surgery. These generally involve use of laparoscopic devices and remote-control manipulation of instruments with indirect observation of the surgical field through an endoscope or similar device. With the reduced trauma associated with minimally invasive surgery, long hospital stays may be reduced with increased rates of short stay or day surgery. Traditionally, cranial base tumors have been removed by making craniotomies or cranial base ostomies, and possibly by removing facial bones. To access these areas, surgeons usually need to make potentially disfiguring incisions in the face and scalp. Sometimes the morbidity from the “open” cranial base approach alone could be significant, even with an uneventful removal of the tumor. At the Center, the endoscopic approaches are usually through the nose or nasal passages (Figure 1), however transoral endoscopic approaches to the cranial base and cervical spine are also performed. Because morbidity from the minimally invasive endoscopic approaches is so low, it becomes possible to treat patients with tumors that were previously considered non-resectable or as having too poor a prognosis for more invasive surgery. Even partial resection of such tumors can relieve pain, preserve function, and permit earlier adjuvant radiation and chemotherapy.

Surgical resection plus stereotactic 125I brachytherapy in adult patients with eloquently located supratentorial WHO grade II glioma – Feasibility and outcome of a combined local treatment concept

The current pilot study analyzed feasibility, risk and effectiveness of 1) microsurgery plus stereotactic iodine-125 ((125)I) brachytherapy (SBT) for large (diameter > 4 cm), circumscribed, and complex located WHO grade II glioma and 2) SBT alone for small (diameter < 4 cm), and complex located recurrences. Lowactivity temporary (125)I seeds were used. The applied reference dose was 54 Gy and the dose rate was low (median, 10 cGy/h). Time to progression and time to additional external beam radiation (EBR) and/or chemotherapy were estimated with the Kaplan-Meier method. Any adverse sequel potentially attributable to treatment was classified as morbidity. Treatment effects of SBT were estimated according to the modified MacDonald criteria. Thirtyone patients (de novo group: n = 18, recurrence group: n = 13) were included. The median tumor volume before surgery was 66 ml. A planned partial tumor resection achieved eligibility for SBT in all patients. Transient morbidity of microsurgery and SBT was 27.8 % and 6.4 %, respectively. There was no permanent morbidity. Radiogenic complications did not occur. Complete response, partial response, and stable disease were seen in 8, 9, and 14 patients, respectively. Ten patients exhibited tumor progression (overall 5-year progression- free survival > 60 %). The 5-year probability to receive chemotherapy and/or EBR was 18 %. A planned partial tumor resection of large and complex located WHO grade II glioma is safe. SBT of small and complex located residual of recurrent tumors is safe and minimally invasive. Combined treatment may provide the possibility to withhold EBR and/or chemotherapy for a considerable number of patients and deserves further prospective evaluation.

Glomangiomatose der Hand. Ein Fallbericht

Glomus tumours are solitary benign lesions most frequently located subungually on fingers and toes. In the rare case of a glomangiomatosis, the typical glomus cells are found on the altered vessel wall of the angiomatosis. Due to the rarity of this disease, no therapeutic golden standard has been mentioned in the literature, and a conservative treatment is usually adopted. The case of a 20-year-old craftsman with congenital, painful glomangiomatosis on his left dominant hand, progressively limiting the functionality of this limb, is reported. Two years after unsuccessful partial tumour resection, a surgical treatment based on radical tumour resection in terms of a finger amputation was performed. The 1-year follow-up showed no signs of pain for the patient.

Minimally Invasive Transpedicular Vertebrectomy for Metastatic Disease to the Thoracic Spine

We present a series of 8 patients with thoracic metastatic disease causing acute neurologic decline. We present minimally invasive posterolateral vertebrectomy and decompression as an effective approach in patients with significant comorbidities and as palliative care. Metastatic disease to the spine is common and frequently occurs in the thoracic vertebrae. Posterior laminectomy alone has generally been found to be ineffective in the management of spinal metastatic disease with neurologic compromise as most compression occurs ventrally. Patients with significant comorbidities are often unable to tolerate extensive surgery involving a thoracotomy. Limited life expectancy and quality of life issues also often argue against extensive surgery. Eight patients (mean age 74 y) with thoracic metastatic disease and acute neurologic compromise underwent a minimally invasive posterolateral vertebrectomy and partial tumor resection. Patients were considered unsuitable for an open anterior approach owing to age, comorbidities, and limited life expectancies. In the operating room, patients were positioned prone. A paramedian incision measuring 3 cm allowed the introduction of sequential dilators and the placement of a 22-mm diameter tubular retractor. Dorsal decompression was accomplished and partial vertebrectomy was performed for ventral decompression. Radiation was used postoperatively in all patients. There were no complications due to the procedure. Improvement of at least 1 grade on the Nurick scale was noted in 5 of 8 (62.5%) patients. Two patients were able to ambulate independently immediately after surgery despite having significant paraparesis preoperatively. Pain improved in 5 of 8 (62.5%) patients postoperatively according to the numerical pain score. Average inpatient length of stay was 4 days after the procedure. Mean blood loss was 227 mL and mean length of the procedure was 2.2 hours. Minimally invasive transpedicular vertebrectomy is an effective palliative treatment option for thoracic metastatic disease in patients not eligible for more extensive anterior transthoracic surgery and stabilization.

Treatment of Optic Pathway Hypothalamic Gliomas in Childhood: Experience With 18 Consecutive Cases

The aim of this study was to present our 17-year experience (1989 to 2006) in the treatment of optic pathway/hypothalamic gliomas (OPHG) in 18 children younger than 17 years (median age, 66 mo). Only 2 of these had evidence of neurofibromatosis-1. OPHG was diagnosed using computed tomography and/or magnetic resonance imaging. Histologic studies showed low-grade astrocytoma (WHO grade I or II) in 16 cases, anaplastic astrocytoma in 1, and oligoastrocytoma (WHO grade III) in 1. Treatment included partial tumor resection in 12 patients, chemotherapy in 5, and radiotherapy in 3. Ophthalmologic and visual alterations occurred in 12 patients, endocrine alterations in 6, and neurologic signs in 5. All treatment modalities led to tumor shrinkage and stabilization for a variable period, but none of them totally eradicated the tumor. Fourteen (78%) of 18 patients had a sustained reduction of tumor size between 6 months and 17 years. The 5-year overall and progression-free survival rates were 80.0% and 63.3%, respectively. Fifty-six percent of patients had endocrinologic sequelae, with growth hormone deficiency being the most common. Two patients died, none with neurofibromatosis-1, with a hypothalamic/chiasmatic tumor with suprasellar extension and accompanying electrolyte abnormalities. Because progression of these tumors is slow and associated with endocrinopathy, we recommend chemotherapy as a primary treatment of OPHG if the disease progresses.

Sustained Clinical Inactivity and Stabilization of GH/IGF-1 Levels in an Acromegalic Patient after Discontinuation of Somatostatin Analogue Treatment

A 38-year-old woman first presented complaining of foot enlargement, finger numbness, arthralgia, fatigue, galactorrhoea and oligomenorrhea. Her symptoms in conjunction with her coarsened facial features and prognathism led to the suspicion of acromegaly. Oral glucose tolerance tests (OGTT) were performed at initial presentation and almost yearly thereafter for a period of 14 years. Pituitary computerized tomographies (CT) were performed annually for the first six years and magnetic resonance imaging every two years thereafter. The diagnosis of acromegaly was confirmed by OGTT at presentation. A pituitary CT revealed a large invasive pituitary macroadenoma. She remained acromegalic after adenomectomy (evidently partial tumor resection), but was controlled with subsequent long-term somatostatin analogue (SRL) administration. After eight years of SRL administration, she had acceptable stabilization of acromegaly and at that point SRL administration was discontinued. The patient maintained the same control for the following six years up to the present time without further SRL administration. This is the first case with stabilization of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) to nearly normal levels and clinical inactivity of acromegaly after withdrawal of long-term treatment with SRLs.

Histopathologic Consideration of Fiducial Gold Markers Inserted for Real-Time Tumor-Tracking Radiotherapy Against Lung Cancer

Internal fiducial gold markers, safely inserted with bronchoscopy, have been used in real-time tumor-tracking radiotherapy for lung cancer. We investigated the histopathologic findings at several points after the insertion of the gold markers. Sixteen gold markers were inserted for preoperative marking in 7 patients who subsequently underwent partial resection of tumors by video-assisted thoracoscopic surgery within 7 days. Fibrotic changes and hyperplasia of type 2 pneumocytes around the markers were seen 5 or 7 days after insertion, and fibrin exudation without fibrosis was detected 1 or 2 days after insertion. Because fibroblastic changes start approximately 5 days after gold marker insertion, real-time tumor-tracking radiotherapy should be started >5 days after gold marker insertion.

Ultrasonic contrast agents in transcranial perfusion sonography (TPS) for follow-up of patients with high grade gliomas

PurposeThe aim of this study was to evaluate brain perfusion differences in patients with high grade gliomas after partial tumor resection and irradiation/chemotherapy between tumor and non-tumor hemisphere by transcranial perfusion sonography (TPS) employing a contrast burst imaging (CBI) technique. MethodsSix patients with glioblastoma (WHO Grade IV) in the temporoparietal region within the defined axial diencephalic scanning plane were examined by TPS during follow-up. All subjects had an adequate acoustic temporal bone window. Transtemporal insonation on brain tumor and non-tumor hemisphere was performed with a bolus-injection of sulphur hexafluoride-based contrast agent (10mg IV, 5mg/ml – SonoVue®, Bracco, Altana, Switzerland). Recorded images were analysed off-line by Quanticon Software (3D-Echotech, Munich, Germany) and time intensity curve parameters [area under the curve (AUC, dBs), peak intensity (PI, dB), time to peak (TTP, s)] in five regions of interest (ROI) [thalamus anterior, thalamus posterior, nucleus lentiformis, white matter, whole hemisphere] were evaluated. Statistical analyses were performed. ResultsPerfusion differences between brain tumor and non-tumor hemispheres were detected with contrast burst imaging (CBI) technique with a significantly greater mean AUC (5343.69dBs vs. 4625.04dBs, p<0.028) and a significantly prolonged TTP (32.72s vs. 28.91s, p<0.046) in the tumor hemisphere. ConclusionWithin our study population, TTP and AUC seem to be the most robust parameters for the evaluation of cerebral perfusion differences assessed by transcranial perfusion sonography with CBI technique. We hypothesize that these results correlate with microvascular changes due to treatment regimens, such as microvessel necrosis after irradiation and chemotherapy. Above that, TPS may be of value for the long-term follow-up of brain tumor therapy concept.

Poster 164: Delayed Symptomatic Cerebral Vasospasm After Partial Meningioma Resection: A Case Report

Setting: Academic tertiary care hospital and acute inpatient rehabilitation hospital. Patient: A 48-year-old woman with a large left petroclival meningioma underwent left retrosigmoid craniotomy with partial tumor resection complicated by subarachnoid hemorrhage (SAH). Case Description: The patient was admitted to our acute inpatient rehabilitation hospital on postoperative day 8 for physical, occupational, and speech-language therapy directed at lower cranial nerve dysfunction and mild right-sided hemiparesis.

Methylguanine Methyltransferase Testing in Glioblastoma: When and How?

Controversy remains on the optimal treatment schedule of the alkylating agent temozolomide (TMZ) in malignant glioma and the value of methylguanine methyltransferase (MGMT) determination. This repair enzyme is key in reverting lethal DNA damage induced by alkylating agent chemotherapy, and in the absence of this enzyme, cells are more susceptible to TMZ. In this issue of the Journal of Clinical Oncology, Chinot et al report on a (too) small phase II study investigating a week-on and week-off dosedense TMZ administration regimen as neoadjuvant chemotherapy before definitive radiation in 29 eligible patients with unresectable glioblastoma. The aim of this alternative dose-dense administration schedule is not only to increase the dose-intensity by more than two-fold, but to overcome drug resistance by depleting the tumor cells of MGMT. In peripheral blood mononuclear cells, it has been shown that repeated and continuous exposure to TMZ will exhaust the cells of MGMT, but whether this also applies to tumor cells remains to be demonstrated. The results of this study were disappointing. Median survival was only 6 months (95% CI, 1 to 11), with only 28% of patients alive at 1 year. Even when considering that this is a poor prognosis group of patients, these results appear inferior to standard therapy, including concomitant chemoradiotherapy, where a median survival of 9 months was reported for patients with unresectable tumors. Chinot et al attempted to determine MGMT expression in 25 patients by immunohistochemistry, choosing an arbitrary cutoff based on the median percentage of cells staining positively. They found that 6 of 11 patients with low MGMT expression, but only one of the 14 patients with high MGMT expression responded. The study emphasizes again the importance of MGMT to predict a response to the alkylating agent therapy. The predictive value of MGMT for benefit from alkylating agent chemotherapy, whether this be a nitrosourea or temozolomide, has now been repeatedly shown. Methylation of the MGMT gene promoter has been found to be a predictive marker for benefit from TMZ treatment in patients treated with temozolomide chemotherapy. Analysis of a representative subgroup of patients in a randomized trial showed that the addition of TMZ only benefited patients with a methylated (and thus silenced) MGMT gene promoter, while overall survival and progression-free survival was comparable for TMZ-treated patients with a functional MGMT gene to patients having been treated with initial radiotherapy alone. Based on this data, one may want to conclude that patients without MGMT promoter methylation should not be treated with alkylating agent chemotherapy. In these patients, TMZ has marginal activity at best, and alternative strategies may offer better chances. However, outside clinical trials, alternative strategies are currently not available. Nevertheless, the treatment, although generally well tolerated, carries its risks for toxicity. Also, in countries without reimbursement for chemotherapy, some patients may choose to forego the expense for temozolomide in the absence of MGMT promoter methylation. Furthermore, this analysis was performed retrospectively, and although very provocative and suggestive, requires prospective validation. In an ongoing Intergroup trial by the Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer (RTOG 0525/EORTC 26052-22053), patients with newly diagnosed glioblastoma are stratified by MGMT methylation status before random assignment to a TMZ administration schedule (standard daily dose for 5 days or a dose-dense treatment for 3 of 4 weeks). To be eligible for this trial, patients must have undergone at least partial tumor resection, and tumor material must be available for centralized MGMT promoter methylation determination. Thus, not only efficient trial management is necessary, but also the goodwill and collaboration of the neurosurgeons and pathologists at many sites. Repeatedly, investigators advocate performing MGMT determination using the simpler immunohistochemistry staining, rather than a methylation-specific polymerase chain reaction assay (MSP) of the function of the MGMT gene. Although some associations may be found by immunohistochemical MGMT expression, this method has many shortcomings. Heterogeneous MGMT expression within tumors, and high levels of MGMT protein present in infiltrating lymphocytes, microglia, and blood vessels limit the reproducibility of the method. More important, MGMT is an inducible enzyme that may be upregulated after chemotherapy or radiotherapy, thus the expression of the protein at diagnosis might not reflect the functional protein during therapy. The MSP assay requires small quantities of DNA that can be extracted from paraffin-embedded tissue samples or, better yet, from cryopreserved tissue samples. In glioma, the presence of a methylated MGMT allele can be attributed solely to the neoplastic cells, irrespective of contamination of nontumor tissue. In our opinion, determination JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 25 NUMBER 12 APRIL 2

Medulloepithelioma: Two unusual locations

Reported herein are two cases of medulloepithelioma (ME) occurring in very unusual locations. Case 1 involved a 44-year-old man who presented with leg pain and urinary incontinence. Spine magnetic resonance imaging (MRI) showed an enhancing epidural and intradural lumbosacral mass. He underwent L3-S2 laminectomy with partial tumor resection. Approximately 2 months following surgery, he developed leptomeningeal spread of the tumor, and died 2 months later. Case 2 involved a 22-month-old girl who presented with painless left proptosis. MRI demonstrated diffuse, fusiform, and contrast-enhancing enlargement of the left optic nerve. Following biopsy, she was treated with chemotherapy. Histologically, the tumors in both cases consisted of primitive pseudostratified neuroepithelial cells, arranged in papillary, tubular, or trabecular configurations. A PAS-stained external limiting membrane (ELM) of the neuroepithelia was present. In case 1 there were scattered cartilaginous nodules within the tumor, in keeping with the diagnosis of a teratoid ME. Immunohistochemically, the tumor cells were positive for synaptophysin, nestin, microtubule-associated protein-2, CD56, CD10, glial fibrillary acidic protein (focal), and S-100 protein (focal). The main differential diagnoses include an immature teratoma and an optic nerve glioma in cases 1 and 2, respectively. Histological demonstration of the ELM by PAS stain is a simple but useful technique.