Optic nerve gliomas. I. Clinical diagnosis and pathology

Summary At the National Institute of Neurosurgery a team of ophthalmologists and neurosurgeons has for 20 years been collaborating in the research and treatment of optic nerve gliomas. Among 34 patients, 30 were under the age of 20 years, and 20 under the age of 10 years. Of the 20 patients younger than 10 years, 16 were girls. The clinical symptoms were classified into three groups: I. Unilateral visual impariment with unilateral axial proptosis (16 patients), strabismus (6 cases), and typical X-ray findings of the skull. II. Uni- or bilateral visual impairment without proptosis (12 patients), depressed vision in the homolateral eye (9 patients), hemianopia (2 out of 4 examined patients) and hemiparesis (6 cases). III. Uni- or bilateral visual impairment without proptosis but with hormonal or metabolic disturbances (6 patients).Carotid angiography and PEG were performed in groups II and III and revealed a picture that is characteristic of suprasellar tumours.^99mTc pertechnetate scanning was done in six cases and showed isotope accumulation in the tumour in five.Pathologically, considering also the clinical aspects, two types of localization merit consideration:1. The relationship between the tumour and the optic nerve (tumours growing within and extending beyond the optic pathways, respectively) and 2. The site of the tumour within the optic nerve (intraorbital, intraorbital and intracranial, intracranial only, chiasmal, and diffuse). Our data of histology and tissue culture prove the benign nature of the tumour even in the recurrences.     

泌尿系统原发性原始神经外胚层瘤临床病理分析

目的 探讨泌尿系统原发性原始神经外胚层瘤(primitive neuroectodermal tumor,PNET)的临床病理特征、免疫学表型、治疗方法及预后.方法 回顾性分析3例泌尿系统原发性PNET患者资料.3例均为男性,年龄分别为29、32和75岁.2例原发于肾脏,1例原发于膀胱.2例肾肿瘤大小分别为7.7 cm×6.2 cm和12.6 cm×9.4 cm,影像学检查提示肿瘤边界尚清,内部回声欠均匀.膀胱肿瘤大小为10.0 cm×10.0 cm,影像学检查提示膀胱壁不规则增厚,其内密度不均匀.2例肾肿瘤行肿瘤根治术,膀胱肿瘤行血块取出术及肿瘤活检术.结果 光镜下,瘤细胞为形态一致的小圆形或卵圆形,被纤维结缔组织分隔成实性片状或巢状,并形成假菊形团或Homer-Wright菊形团,核分裂象多见.免疫组化标记:3例肿瘤CD99、突触素和波形蛋白均为阳性.1例肾肿瘤Ki67阳性率＜5%,另1例80%阳性.3例病理诊断均为PNET.例1肾肿瘤患者未行化疗,于术后14个月复发死亡;例2肾肿瘤及例3膀胱肿瘤患者术后予以化疗,分别于术后4、6个月死亡.结论泌尿系统原发性PNET是一种少见的高度恶性软组织肿瘤,诊断主要依据病理形态学特征及免疫组化标记.目前治疗方法主要是手术加放、化疗.

Abstract：

Objective To explore the clinico-pathological features, immunophenotype, treatment and prognosis of urologic primary primitive neuroectodermal tumor (PNET). Methods The clinical data of 3 patients with urologic PNET were analyzed retrospectively. All patients were male, aged 29, 32 and 75 years respectively. Two of the lesions were located in the kidney, and the third was located in the bladder. The sizes of renal tumors were 7.7 cm×6.2 cm and 12.6 cm×9.4 cm respectively. Imaging examinations revealed a well-defined mass with inhomogeneous echo inside. The size of bladder tumor was 10.0 cm×10.0 cm. CT scan demonstrated irregular thickening of the bladder wall, and the density of the wall was inhomogeneous. In the 2 cases of renal PNET radical surgery was performed, while an emergency palliative surgery to remove a blood clot and biopsy were performed in the bladder PNET case. Results In light microscope, the tumors were characterized by uniform small round or oval cells and nest-like or dense sheet structures surrounded by sparse fibrovascular stroma. Homer-Wright rosettes or pseudorosettes were observed, as well as mitoses. Immunohistochemical study revealed that all cases showed positive staining for CD99, synaptophysin and vimentin. One of the renal tumor cells showed positive for CD56, and the other renal tumor and urocystic tumor cells were focally positive for chromogranin A. Additionally, in 1 of the cases of renal tumor there was a high positive rate of 80% for Ki67 staining while the other case showed less than 5%. All 3 cases were eventually diagnosed as PNET. The first renal tumor case was not treated with radiotherapy and chemotherapy postoperatively, and the patient died of recurrence 14 months after surgery. Both the second renal tumor case and the bladder tumor case underwent chemotherapy postoperatively, and they died 4 and 6 months after surgery respectively. Conclusions The urologic primary PNET is a very rare, highly malignant soft tissue tumor, and the diagnosis must be based on pathologic findings and immunohistochemical phenotypes. The multimodal treatment for urologic primary PNET consists of surgery, chemotherapy and radiotherapy.     

Organ-confined primitive neuroectodermal tumor arising from the kidney

Primitive neuroectodermal tumor (PNET) of the kidney is a rare entity with high malignant potential. Of the reported cases of renal PNET, patients presented with metastatic disease and had a poor response to therapy. The authors describe a rare case of an organ-confined primary PNET arising from the kidney in a 16-year-old girl who presented with vague abdominal pain. Tumor behavior and treatment modalities are discussed.     

The role of anticonvulsant medications in the management of patients with anaplastic gliomas

All 100 patients in a protocol of therapy for anaplastic gliomas were studied with regard to occurrence of seizures preoperatively and postoperatively. Patients without a history of seizures preoperatively had a similar incidence of seizures postoperatively, whether anticonvulsant medications were prescribed prophylactically or not.     

基质金属蛋白酶及其抑制因子在边缘系统胶质瘤中的表达

目的探讨基质金属蛋白酶(MMPs)MMP2、MMP9及其组织抑制因子(TIMPs)TIMP2在边缘系统胶质瘤侵袭过程中的作用。方法利用免疫组织化学方法检测MMP2、MMP9及TIMP2在35例高、低级别胶质瘤和20例脑膜瘤中的表达。结果①MMP2及MMP9在高级别胶质瘤中的表达明显高于低级别胶质瘤,在低级别胶质瘤中的表达明显高于脑膜瘤,差异有显著性。②TIMP2在高级别胶质瘤中的表达明显低于低级别胶质瘤,在低级别胶质瘤中的表达明显低于脑膜瘤,差异有显著性。结论①MMP2及MMP9的表达与胶质瘤的恶性程度有关,可能成为胶质瘤恶性程度和预后的判断指标。②TIMP2是MMP2的抑制因子,两者之间失衡是促进胶质瘤侵袭的重要因素之一。     

Primary primitive neuroectodermal tumor (PNET) of the kidney with venous thrombus

Primitive neuroectodermal tumors of the kidney are rare, the diagnosis usually being made at histopathology. A young adult presented with a painful left renal mass. CT Scan of the abdomen revealed a large necrotic tumor of the left kidney. At surgery the patient was found to have a venous thrombus confined to the renal vein. Radical nephrectomy was done. Histopathology showed a round cell neoplasm with typical Homer Wright rosette formation and positive staining for neuron specific enolase (NSE) and MIC-2 on immunohistochemistry. The patient is undergoing multidrug chemotherapy and is alive and well at a follow up of nine months.     

Primary primitive neuroectodermal tumor of the kidney: A case report

There are nearly 50 PNET cases in the literature with primary renal localization. The mean age for renal PNET is 28 but it can be seen in a wide range between 4 and 69 years. In this atypical localization PNET may be mistaken with a variety of small round cell tumors, particularly with blastema predominant Wilms’ tumor and due to its distinctive prognostic and therapeutic features differential diagnosis is very important. Immunohistochemical studies are useful in discriminating PNET from other renal small round cell tumors. Renal PNETs tend to metastasize at early stages and they have a high rate of recurrence. Our case is a 45-year-old male presented with left flank pain and hematuria. In computerized tomography a mass in left kidney was observed and nephrectomy was performed. Histopathologic examination revealed a small round cell tumor with rosettes and pseudorosettes. Immunohistochemically the lesion was diffuse strong positive with CD99 and NSE, negative with LCA, pancytokeratin, vimentin, desmin, smooth muscle actin, chromogranine A and S-100. At the time of diagnosis the pathologic stage of the tumor was T1aN0Mx. The patient did not take any further therapy and in 1-year follow-up no local recurrence or distant metastasize occurred.     

Photodynamic therapy in the management of malignant gliomas: a review

Interest in photodynamic therapy in the treatment of malignant gliomas began in the 1950s. Following the publication of papers showing that haematoporphyrin was excluded from the intact blood-brain barrier and that glioma cells grown in culture and subcutaneously could be killed by a combination of light and haematoporphyrin, a number of clinical trials was started, none of which has shown any measurable improvement in patient survival. The reason for this may relate to a lack of understanding of the mechanisms of photodynamic therapy and a lack of the scientific data needed to optimize photodynamic selectivity. This review discusses the potential role of photodynamic therapy in glioma treatment, and reviews the current clinical and experimental work in the field.     

Intralesional administration of I-131 labelled monoclonal antibodies in the treatment of malignant gliomas

Summary The authors report their preliminary experience with the use of radiolabelled monoclonal antibodies (MAb) as an adjuvant treatment for 33 malignant gliomas. MAbs employed in this study are raised against Tenascin (TN) which is an antigen of the extracellular matrix of the tumour. It has also been found in neoplastic cells but never in normal brain tissue. This therapy is aimed to give a local high dose radiation (boost) while sparing healthy brain structures.This treatment has always been well tolerated and no adverse reactions at the level of CNS or major extraneural organs has been observed. Significant improvement of median survival has been obtained but this result should be cautiously evaluate since the study is non-randomized. Comparison with other current adjuvant technique is briefly discussed.     

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience

Summary In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours.In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.Abbreviations AA anaplastic astrocytoma - ACNU (l-4-amino-2methil-5pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea - AraC cytosine arabinoside - AZQ aziridinylbenzoquinone - BCNU 1,3-bis(2-chloroetyl)-1-nitrosourea - BTSG Brain Tumor Study Group (USA) - BTCG Brain Tumor Cooperative Group (USA) - BUdR 5-bromodeoxyuridine - CCNU 1-(2-chloroethyl)-3cyclohexyl-1 -nitrosourea - CDDP cisplatin - DAG dianhydrogalacticol - DBD dibromodulcitol - DTIC imidazolcarboxamide - EORTC European Organization for Research on Treatment of Cancer - 5-FU fluorouracil - GBM glioblastoma - HU hydroxyurea - MeCCNU methyl-CCNU - Miso misonidazole - MP 6-mercaptopurine - MST median survival time - MTTP median time to tumor progression - PCNU 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea - PCZ procarbazine - RT radiotherapy - VCR vincristine - VM26 teniposide - VP16 etoposide     

Primary primitive neuro-ectodermal tumor of cauda equina with intracranial seeding

Summary Primitive neuro-ectodermal tumor (PNET) of the cauda equina is a rare entity. 18 cases have been reported in the literature so far, including 4 cases with intracranial seeding. Moreover parenchymal involvement of brain has never been reported as a form of intracranial seeding from PNET of the cauda equina. A 31 year-old female patient, with PNET of cauda equina showing intracranial seeding 6 months after surgery, is presented in this report. To our knowledge, this is the first adult case of spinal cord PNET with parenchymal involvement of brain. The histopathological, clinical and radiological findings as well as treatment of the patient were evaluated.     

Pyruvate kinase in human brain tumours. Its significance in the treatment of gliomas

Summary Pyruvate kinase isozyme distribution was studied in 101 intracranial tumours of various nature and origin, and in normal human brain (both foetal and adult). In foetal brain, five different forms could be detected by electrophoresis (K₄, K₃M, K₂M₂, KM₃, and M₄). In adult brain, the M₄ type, K₃M hybrid, and K₄ are present; the M type is largely predominant. Alanine inhibition of pyruvate kinase can be used to discriminate between M and K-type pyruvate kinase. The results obtained in an alanine inhibition test are in agreement with the electrophoretic pattern. Pyruvate kinase from foetal brain and brain of a newborn is more inhibited compared with pyruvate kinase from adult brain. In adult brain a high residual activity of pyruvate kinase is found in the presence of alanine. Well differentiated neuroepithelial tumours,i.e., astrocytomas, oligodendrogliomas, and ependymomas showed also relatively high residual activities, though less than in normal adult brain. On the contrary, in poorly differentiated gliomas low residual activity was found. Alanine inhibition of pyruvate kinase correlates well with degree of differentiation of these tumours. There is also a strong correlationship between alanine inhibition of pyruvate kinase and one year survival after total or subtotal resection of gliomas in adults.When in gliomas the residual activity is determined not in the centre of the tumour but more towards the periphery, much higher residual activity is found. It is suggested that brain biopsies in which a residual activity higher than 70% is found probably contain no tumour in the paraffin slides.Poorly differentiated gliomas were characterized by the presence of type K, and the hybrids K₃M. In well differentiated gliomas, besides K₄ and K₃M, M₄ was also present. Alanine inhibition was in agreement with the electrophoretic pattern in all tumours. In children (age 1–11 years) gliomas showed no correlation between the distribution of pyruvate kinase isozymes and the histological classification and grading. Of the non-neuro-epithelial tumours studied relatively high residual activities were found for pyruvate kinase in haemangioblastomas, chromophobe adenomas, and craniopharyngiomas. This was also found in an arteriovenous malformation. Other non-neuroepithelial tumours showed much less residual activity. These included benign tumours, meningiomas, neurilemmomas, malignant metastatic tumours, and fibrosarcomas. It was also found in cavernomas. The determination of pyruvate kinase activity in the presence of alanine may be useful for the diagnosis and treatment of intracerebral tumours, in particular gliomas of adults.The alanine inhibition test is a reliable quantitative procedure. It can be performed in 10 minutes, and may well fit in the scope of a surgical procedure.     

An unusual case of bilateral primitive obstructed megaureters due to ureteral valves presenting with anuria at the age of 1 month

Ureteric valves represent a very rare etiology of ureteral obstruction. We experienced an unusual case of bilateral distal ureteric valves that presented as bilateral primitive obstructed megaureters with anuria at the age of 40 days. To our knowledge, this is the second case of bilateral involvement of distal ureteric valves reported in the literature. Bilateral ureteral valves should be included in the differential diagnosis of bladder outlet obstruction, as well as bilateral primitive obstructed megaureters in children. Excision and ureteral reimplantation is curative.     

Persistent primitive hypoglossal artery with retrograde flow from the vertebrobasilar system: a case report

The persistent primitive hypoglossal artery (PPHA) is one of the pairs of arterial connections that exist in the human embryo between the developing anterior and posterior circulation. Normally the PPHA arises from the cervical internal carotid artery (ICA) and passes through the hypoglossal canal to join the caudal basilar artery (BA). In most cases the vertebral arteries (VA) are either hypoplastic or aplastic and the posterior communicating arteries (PComA) are absent; thus, the main supply to the posterior circulation comes from the internal carotid via the PPHA in an antegrade fashion. Atherosclerotic plaques in the ICA and PPHA present with ischemic symptoms of both the carotid and vertebrobasilar systems. We report a case of a 53-year-old female who presented with a transient episode of left lower extremity numbness and weakness. Work-up with computed tomography (CT) and magnetic resonance imaging (MRI) showed a small watershed infarct in the right middle cerebral artery (MCA)/posterior cerebral artery (PCA) territory. Diagnostic angiography revealed severe proximal stenosis of the cervical ICA and presence of a PPHA just above the stenosis with retrograde filling from the vertebrobasilar junction to the distal cervical ICA. The patient underwent a carotid endarterectomy with intraoperative EEG monitoring. Intraoperative blood flow measurements were made before and after endarterectomy showing evidence of reversal of blood flow to a normal antegrade fashion. The postoperative angiogram showed resolution of the right ICA stenosis and persistence of the PHA. To our knowledge this is the first case report of a PPHA exhibiting reversal of blood flow from the posterior into the anterior circulation. Awareness of this embryological anomaly and its interaction with acquired atherosclerotic disease will minimize misinterpretation of vascular diagnostic studies.     

Classification of gliomas and medulloblastomas using the new TNM system for cerebral tumors

In 1987 the UICC presented a proposal for TNM classification of brain tumors. This proposal is assessed in a retrospective study on 316 glioma and medulloblastoma patients treated in the Neurosurgical Clinic of the University Münster. It is evident that the T categories do not produce the correct sequence of prognostic differentiation required. The features of tumor spread used for classification are not of equal significance for the various types of tumors. In our opinion it is not possible to adequately describe the greatly varying development characteristics of all brain tumors using one system of classification.     

Cytogenetic analysis of gliomas by in situ hybridization of stereotactic biopsy material

Summary Chromosome analysis of brain tumours can provide important pathobiological data; however, cytogenetic tools are so far not routinely applied for diagnosis. In the present study 25 paraffin embedded stereotactic biopsies from 19 glioma patients were studied using in situ hybridization of chromosome #10 and #15 using biotinylated pericentromeric probes. Numerical changes of chromosome #10 are frequent alterations in glioblastoma. Quantification of chromosome #15 served as a control in order to exclude artificial monosomies or nonspecific changes. The number of chromosomes in at least 200 cells were counted for each specimen. 18 of 25 biopsies could be evaluated quantitatively. The small volume of probes was not a limiting factor for analysis. Quantification of nonspecific chromosome #15 revealed single spots in 22–41% of all cells in the 18 biopsies. Chromosome #10 showed single spots in a range between 34 and 44% of counted nuclei in 13/18 biopsies. In 5 out of 18 biopsies 51–60% monosomies were found; in this subgroup were 4 high grade gliomas. These cases were interpreted as monosomy of chromosome #10. The results demonstrate feasibility and quantitative evaluability of cytogenetic analysis in Stereotactic biopsy material using in situ hybridization.     

Biological behavior of the primitive neuroectodermal tumors: significant supratentorial childhood gliomas.

Supratentorial gliomas in the pediatric age group at the University of Kentucky Medical Center accounted for 20% of all childhood brain tumors. Seventeen of the 20 children with these tumors, regardless of histologic type, mode of therapy, or other parameters died within five years after tissue diagnosis, and most were dead within two years. Unlike the astrocytic gliomas, the poorly differentiated primitive neuroectodermal tumors tended to spread diffusely throughout the central nervous system and accounted for 35% of the supratentorial gliomas in children at our institution. Results of this study suggest that therapy for the primitive neuroectodermal tumor, unlike other childhood supratentorial gliomas, should be considered for the entire neuraxis.     

Pathological correlation of CT ring in recurrent, previously treated gliomas

The meaning of the enhancing ring commonly seen on computerized tomographic (CT) scans in patients with recurrent, treated glioblastoma has long been of concern. Does the ring represent radiation necrosis, pseudocapsule formation, compressed adjacent brain, or, in fact, a peripheral zone of viable tumor? We employed a multiple intratumoral biopsy technique at the time of reoperation to investigate this ring. Pathological evidence is presented documenting the content of the ring to be viable tumor. It is suggested that perhaps treatment failure may be determined on sequential CT examinations by comparing the volume and degree of contrast enhancement.     

Resorption of peritumoural oedema in cerebral gliomas during dexamethasone treatment evaluated by NMR relaxation time imaging

Summary Peritumoural brain oedema is a prominent feature of malignant brain tumours. Glucocorticoids diminish the neurological symptoms and signs caused by the oedema and reduce the abnormally high cerebral water content. The exact mechanisms of action of the glucocorticoids are unknown.The present study investigates the influence of dexamethasone on NMR relaxation time T₁ in peritumoural oedema in 13 patients with gliomas. It is shown that NMR T₁ images can be used as a potent monitor of brain oedema, and that dexamethasone significantly reduces mean T₁ after 1, 3, and 7 days of treatment by 2%, 6%, and 13% respectively.Using an image histogram analysis technique the term superoedema was defined as the 50% of the total oedema area with the highest t₁, corresponding to the highest water content. It is shown, that with this technique the treatment effect of steroids on superoedema was a reduction of 13%, 33%, and 57% after 1, 3, and 7 days of treatment respectively. The mean change after 24 hours of treatment was statistically significant (p < 0.01).The method can be used in all situations where the anti-oedematous effect of a given treatment is to be monitored.