原发性中枢神经系统生殖细胞肿瘤临床病理分析17例报告

目的探讨原发性中枢神经系统生殖细胞肿瘤临床病理特点。方法收集17例原发性中枢神经系统生殖细胞肿瘤,分析、总结其临床病理特点。结果17例中枢神经系统生殖细胞肿瘤病人中15例生殖细胞瘤,1例畸胎瘤,1例混合型生殖细胞肿瘤。年龄7～30岁,男性13例,女性4例。发生于松果体4例,鞍区3例,鞍上2例,丘脑2例,第三脑室5例,脊髓髓内1例。常见症状：头痛、恶性、呕吐；复视、视野缺失；多饮、多尿；双下肢无力、行走不稳,麻痹等。其中伴有性早熟4例,生长发育迟缓1例,性功能减退1例,闭经1例。巨检肿瘤多呈灰白色、实质性。镜下肿瘤细胞多角形,胞浆空泡状,细胞核大,核仁明显,核分裂相可见,间质伴有淋巴细胞浸润。17例病人均经手术治疗,术后辅以放疗。12例病人平均随访4．3年,11例存活。结论中枢神经系统生殖细胞肿瘤罕见,组织学上类似于性腺来源生殖细胞肿瘤,几乎全部发生于身体中线部位。主要发生于少年儿童。免疫组化PLAP阳性有助于诊断。该疾病对放疗极其敏感,预后良好。     

Mixed germ cell tumors in septum pellucidum after radiochemotherapy of suprasellar germinoma: de novo metachronous or recurrent neoplasms?

Introduction  Mixed germ cell tumors (GCTs) consisting of a germinoma and a mature teratoma in the septum pellucidum have never been described previously; the patient we present here is the first reported example. Case report  This case involves an 18-year-old man who presented with abnormal behavior, impairment in recent memory, and emotional change. Five years ago, he received five cycles of chemotherapy using cisplatin and ectoposide and 24G of local radiotherapy for clinical diagnosis of suprasellar germinoma in another hospital. The tumor was then completely resolute. Magnetic resonance imaging in our hospital revealed a large fatty mass located primarily in the septum pellucidum and some portions of the corpus callosum; a heterogeneous enhancing tumor was observed in the surrounding area. The second tumor was completely removed. The histological diagnosis was mixed GCTs containing the component of a germinoma and a mature teratoma. Conclusion  This case is characterized by a second GCT occurring at a different site and with a different histological type, long after complete resolution of suprasellar germinoma. Although it is very difficult to draw conclusions about the correlation between the first and second GCTs, neurosurgeons should always pay attention to the pathological variety and dynamic pathological changes in GCTs once they start to examine and treat them.     

中枢神经系统生殖细胞肿瘤11例临床分析

目的总结中枢神经系统生殖细胞肿瘤临床表现、检查和治疗特点。方法1997年至2007年共治疗11例，治疗方法有手术、放射治疗和化学治疗。结果术后单纯放疗7例有效率为71．43％。术后放疗结合化疗9例有效率为88．89％。结论手术联合化疗和放疗的综合性治疗可提高中枢神经系统生殖细胞肿瘤的疗效。     

Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression

Podoplanin (aggrus) is a mucin-like transmembrane sialoglycoprotein that is expressed on lymphatic endothelial cells. Podoplanin is putatively involved in cancer cell migration, invasion, metastasis, and malignant progression and may be involved in platelet aggregation. Previously, we showed upregulated expression of podoplanin in central nervous system (CNS) germinomas, but not in non-germinomatous germ cell tumors, except for parts of immature teratomas in limited numbers. However, little information exists about its role in CNS astrocytic tumors. In this study, 188 astrocytic tumors (30 diffuse astrocytomas, 43 anaplastic astrocytomas, and 115 glioblastomas) were investigated using immunohistochemistry with an anti-podoplanin antibody, YM-1. In 11 of 43 anaplastic astrocytomas (25.6%) and in 54 of 115 glioblastomas (47.0%), podoplanin was expressed on the surface of anaplastic astrocytoma cells and glioblastoma cells, especially around necrotic areas and proliferating endothelial cells. However, the surrounding brain parenchyma was not stained by YM-1. On the other hand, podoplanin expression was not observed in diffuse astrocytoma (0/30: 0%). Furthermore, we investigated the expression of podoplanin using quantitative real-time PCR and Western blot analysis in 54 frozen astrocytic tumors (6 diffuse astrocytomas, 14 anaplastic astrocytomas, and 34 glioblastomas). Podoplanin mRNA and protein expression were markedly higher in glioblastomas than in anaplastic astrocytomas. These data suggest that podoplanin expression might be associated with malignancy of astrocytic tumors.     

Pineal germ cell tumors: Two cases with review of histopathologies and biomarkers

Pineal germ cell tumors (GCTs) are primarily seen in pediatric and Asian populations. These tumors are divided into germinomatous and non-germinomatous GCTs (NGGCTs). GCTs are thought to arise by misplacement of totipotent stem cells en route to gonads during embryogenesis. Intracranial GCTs display an affinity to develop along the pineal-suprasellar axis and have variable manifestations dependent upon the location of the tumor. Management and outcomes are driven by histopathologies. In this study, we highlight two cases of pineal GCTs and present a review of the literature with an emphasis on histopathologies and biomarkers.     

Treatment of germ cell tumors in the pineal region

The authors retrospectively analyzed 107 patients with primary intracranial germ cell tumor (GCT), who were treated at the Department of Neurosurgery, Yonsei Medical Center between January 1986 and January 1996. The incidence of GCT was 2.8% in pediatric patients with intracranial tumor. Of the 107 tumors, 60 were located in the pineal region, 30 in the suprasellar region, 16 in basal ganglia or the thalamic region, and 1 in the posterior fossa. The 60 pineal GCT consisted of 39 germinomas (29 pure germinomas, 6 germinomas with STGC, 4 germinomas mixed with teratoma), 5 mature teratomas, and 16 nongerminomatous GCT. Thirty patients underwent surgery: their operations took the form of total resection in 14 cases, subtotal resection in 10, and biopsy in 6. Thirty patients (27 with germinomas, 3 with endodermal sinus tumors) were managed without surgery on the basis of radiological findings and tumor markers. The 5-year survival was 91% for 39 patients with germinomas, 80% for 5 with mature teratomas, and 49% for 16 with nongerminomatous GCT. Univariate analysis of prognostic factors with the Kaplan-Meier survival curve showed that histological tumor type, radiological findings, results of tumor marker studies, and response to trial radiation or chemotherapy were highly correlated with outcome. Chemotherapy was beneficial as the method of trial treatment in pineal GCT and treatment in recurrent tumors. The administration of trial chemotherapy or radiotherapy without tissue biopsy is well justified as a treatment modality in pineal GCT suspected on the basis of radiological findings and tumor marker studies. Aggressive multimodality approaches with surgery, radiotherapy, and chemotherapy are necessary to improve the outcome in these tumors. We propose new protocol for treatment of germ cell tumors in the pineal region, which is based on a minimally invasive approach.     

六例被长期误诊的脑实质内生殖细胞性肿瘤的MRI特点

目的探讨脑实质内生殖细胞性肿瘤（GCT）的MRI特点。方法回顾分析6例被长期误诊的脑实质内GCT患者MRI的动态变化，每例患者至少接受2次MRI平扫和1次增强扫描。结果初次MRI检查4例表现为软化灶，2例表现脱髓鞘样改变，无占位性病变；5例患者在确诊时出现占位性病变，分别位于基底节区和胼胝体，囊性变多见，病灶有明显增强；5例患者出现病灶侧大脑脚萎缩，3例出现病灶侧的皮层萎缩，多数在首次MRI检查时已出现。结论脑实质内GCT早期常无占位性病变，容易导致同侧皮层和大脑脚的萎缩，往往到晚期才出现占位性病变，是早期误诊的主要原因。     

松果体区生殖细胞肿瘤放射外科治疗的合理性探讨

目的 探讨立体定向放射外科作为一线方案治疗松果体区生殖细胞肿瘤的合理性.方法 回顾性分析14例经伽玛刀或X-刀治疗的松果体区生殖细胞肿瘤患者的临床资料,重点研究肿瘤放射外科治疗后变化及复发、转移情况.结果 14例患者于放射外科治疗后11 d至106个月再次入院.肿瘤放射外科治疗后缓慢增大1例,无明显变化2例,缩小后再增大1例,基本消失后原位复发2例,消失后周边复发4例,原位复发并种植转移2例,原位消失但出现种植转移2例.病理为:生殖细胞瘤5例、混合型生殖细胞肿瘤4例、成熟畸胎瘤3例、非成熟畸胎瘤和卵黄囊瘤各1例.结论 放射外科不能作为松果体区生殖细胞肿瘤的单一治疗方法.假使已采用放射外科治疗,则应依据肿瘤标记物结果和治疗后肿瘤的变化情况,及时手术或综合治疗.

Abstract：

Objective To discuss the rationality of the stereotaxic radiosurgery as the first therapy strategy on pineal region germ cell tumors.Methods To retrospectively analyze the clinical materials of 14cases which received the treatment of gamma knife or X- knife.The condition of tumor changing,recurring and metastasize post- radiosurgery were emphasized.Methods All the patients of 14 cases were admitted again from 11 days to 106 months after which had received radiosurgery.The tumor increasing slowing with 1cases,no marked change with 2 cases,repeated increasing after diminution with 1 case,situ recur after essential disappear with 2 cases,ambitus recur after disappear with 4 cases,situ recur and implantation metastasis 2 cases,situ disappear but implantation metastasis with 2 cases.The pathology results were 5germinomas,4 mixed germ cell tumors,3 mature teratomas,1 unmature teratoma and 1 yolo sac tumor.Conclusion Radiosurgery cant be regarded as the exclusive treatment for pineal region germ cell tumors.If the patients received the radiosurgery,they should be operated or combined therapy in time according the results of tumor marker and the condition of tumor changing.     

Suprasellar germ cell tumors in the dog: a report of five cases and review of the literature

Summary Suprasellar germ cell tumors were identified in five young adult to middle-aged dogs. Clinical signs included depression, mydriasis, ptosis and visual deficit. At necropsy large extramedullary masses were found on the ventral surface of the rostral brain stem. Histologically four were characterized by sheets and nests of moderately pleomorphic round cells resembling seminoma, admixed with larger vacuolated cells, glandular formations with secretory material, and occasional foci of squamous differentiation. The fifth case was more homogenous, with germinomatous elements predominating. Immunohistochemical examination of three tumors revealed positive staining for alpha fetoprotein. Although only one case showed intracranial metastasis, these tumors were considered malignant due to the marked local invasion and destruction. The veterinary literature is reviewed, and we propose that two tumors previously reported as craniopharyngioma be reclassified as germ cell tumors. One other tumor previously reported as an unclassified suprasellar tumor was identified, which also demonstrated features of a germ cell tumor.     

Germ cell tumors of the CNS in children: recent advances in therapy

Primary germ cell tumors of the central nervous system are rare neoplasms, accounting for no more than 2% of all malignancies in children and young people under 20 in the Western hemisphere. They have unique features related to age at diagnosis and sites of origin, as well as race and gender predilection. Prognosis has been clearly shown to be strongly related to pathological classification as either pure germinoma or nongerminomatous germ cell tumor, although many of these lesions are comprised of mixed elements. The presence of serum or cerebrospinal fluid tumor marker elevation has been an essential determinant of response to treatment. Because of the deleterious effects of irradiation on the immature nervous system, investigators have used chemotherapeutic strategies that either reduce or eliminate radiation therapy. In this article, we review the most recent advances in therapy for CNS germ cell tumors in the pediatric population and highlight the importance of cooperative trials in this setting. Received: 12 April 1999     

人绒毛膜促性腺激素在脑实质生殖细胞肿瘤诊治中的意义

目的研究脑实质生殖细胞肿瘤(GCT)患者脑脊液和血清中人绒毛膜促性腺激素(HCG)水平变化,评价其在肿瘤诊断、疗效监测中的意义。方法对5例脑实质内GCT患者的脑脊液和血清HCG水平在治疗前后进行系列测定。以10例性别年龄匹配的因其他疾病接受腰穿检查的患者作为对照组,测定其脑脊液HCG水平。观察脑脊液和血清HCG水平在治疗前后的变化情况。结果10例对照组患者的脑脊液中均测不到HCG。从5例GCT患者共采集17对脑脊液和血清配对样本。所有5例患者都出现脑脊液和血清HCG水平升高。治疗后脑脊液和血清HCG水平迅速下降。血清和脑脊液HCG水平呈显著相关。每一对样本中,脑脊液HCG水平均高于血清。血清、脑脊液HCG水平比为0.245±0.190。结论脑脊液HCG升高对诊断脑实质内GCT具有高度特异性和较高灵敏度。对分泌HCG的GCT,脑脊液和血清HCG是评价治疗效果和监测肿瘤复发的重要指标。     

Germ cell tumors of the thalamus and the basal ganglia

Two cases of germ cell tumors (GCTs) of the basal ganglia are presented and 40 previously reported cases are reviewed. The incidence of GCTs of the basal ganglia and thalamus was estimated as less than 14% of all intracranial GCTs. All patients except for two (95%) were male, aged 7–19 years. The clinical course was usually slow. The major symptoms were hemiparesis, mental deterioration such as dementia or character change, precocious puberty, diabetes insipidus, oculomotor palsy, speech disturbance, and hemianopsia. Signs of intracranial hypertension did not occur until the late stages of the disease. The plain CT finding was characterized by an irregularly defined, slightly high-density area frequently accompanied by central low-density areas without significant mass effect. The tumors showed mild to moderate and nonhomogeneous contrast enhancement. An ipsilateral cerebral hemiatrophy was often found. MR images demonstrated the corresponding findings. GCTs of the basal ganglia had a high possibility of containing components other than germinoma such as choriocarcinoma, endodermal sinus tumor, and embryonal carcinoma. Thus, tumor markers in the serum, CSF, or cyst fluid were frequently positive. With recent refinement of microsurgical techniques as well as immunohistochemical study and measurements of tumor markers of serum, CSF, and cyst fluid, major resections of tumor, accurate pretreatment histologic diagnosis, and early determination of the specific types of this tumor appear to be readily possible. This is essential for effective treatment of patients not only with radiosensitive germinoma, but also those with radioinsensitive nongerminoma variants and a combination of them located in this region.     

Is histological diagnosis necessary to start treatment for germ cell tumours in the pineal region?

The significance of histological diagnosis was retrospectively investigated in the treatment of 79 consecutive patients with pineal region tumours. Histological diagnoses were consistent with clinical diagnoses in 38 out of 39 patients with germ cell tumours and in all eight patients with non-germ cell tumours. The single exception was pineoblastoma. Forty-one patients were treated under a clinical diagnosis of pineal germ cell tumour using neoadjuvant chemotherapy and radiation therapy without histological verification. Of the 41 patients, 32 achieved an excellent response, whereas nine required the delayed resection of a residual tumour. Of these nine tumours, seven were mature or immature teratomas or scars. These patients had elevated levels of tumour markers. Most cases of pineal germ cell tumour could be identified on the basis of clinical findings only, and could be treated appropriately using neoadjuvant chemotherapy and radiation therapy without histological diagnosis. However, second-look surgery should be considered in cases with residual teratomatous components or unusual responses.     

Mixed germ cell tumour of the central nervous system with multiple metastases—a 5-year history. A case report

After a 4-month history of intermittent headache an intrasellar benign teratoma was found and totally removed in a 19-year-old male patient who became symptom-free. Three years later a third ventricle germinoma developed which was also totally removed, followed by local radiotherapy. Eight months later a spinal tumour evolved, chemotherapy and radiotherapy resulted in full recovery. Eighteen months later a frontal meningeal tumour appeared and was treated by chemotherapy. Three months later—with chemotherapy—tumorous meningitis developed and the patient died 5 years after the first operation. The results of tumour-markers monitoring, histology, electronmicroscopy and immunohistochemistry referred to a germinoma with multiple metastases and meningeal seeding after total removal of an intrasellar mature teratoma.     

Mdm2和p53基因在颅内非生殖细胞瘤性生殖细胞肿瘤中的表达意义

目的 研究鼠双微基因2(mdm2)基因和p53基因在颅内非生殖细胞瘤性生殖细胞肿瘤患者(NGGCTs)中的表达及意义. 方法 利用半定量RT-PCR技术检测了15例NGGCTs肿瘤(成熟畸胎瘤6例,未成熟畸胎瘤5例,卵黄囊瘤2例,绒毛膜上皮癌2例)中mdm2和p53 mRNA的表达,并与正常人群进行比较,另外检测p53基因5～8外显子的突变情况.结果 p53和mdm2mRNA在各类NGGCTs中均有较高水平表达,与正常对照组比较差异有统计学意义(P=0.000);p53mRNA在各类肿瘤中表达强度差异无统计学意义(P=0.056);mdm2基因在非生殖细胞瘤性恶性生殖细胞肿瘤(NGMGCTs)中表达强度较成熟畸胎瘤高,差异有统计学意义(P=0.000);mdm2和p53mRNA的表达强度无显著相关性(r=0.418,P=0.121);15例NGGCTs肿瘤均未检测到p53基因的突变.结论 mdm2基因异常表达与NGMGCTs肿瘤关系密切,p53基因突变并非NGGCTs形成的主要原因,mdm2和p53之间相互作用共同影响NGGCTs肿瘤的发生发展过程.     

Intracerebral transplantation of dissociated central nervous system tissue suspensions: use of phaseolus vulgaris leucoagglutinin as a cell marker

Successfully transplanted neurons and their sprouting processes were demonstrated by Phaseolus vulgaris leucoagglutinin (PHA) marking. PHA is transported anterogradely and readily reveals the post-transplantation growth of the neuronal processes. Suspensions of fetal central nervous tissue, prepared by dissociation of embryonic rat brain, were marked with PHA and then transplanted into the striatum of nonimmunosuppressed young adult rats. At various intervals thereafter (1 day, 2 days, 1 week, 2 weeks, 1 month, and 2 months), the animals were sacrificed for histological examination with PHA and tyrosine hydroxylase (TH) immunohistochemistry. Up to 2 weeks after transplantation, PHA immunohistochemistry was capable of demonstrating grafted neurons and their presumably regenerated neuronal processes. However, at periods 1 month or longer after transplantation, PHA immunohistochemistry was unreliable. Thus, the PHA marking method has limitations in terms of its retention period, when applied to the intracerebral transplantation of dissociated cell suspensions. Nevertheless, the method presented here can be utilized to study neuronal regeneration as well as the relationship between transplanted neurons and the host tissue.     

Pathophysiological mechanism of ipsilateral cerebral and brainstem hemiatrophy in basal ganglia germ cell tumors: case report

Introduction  The basal ganglia is an uncommon location for germ cell tumors. It has been reported that basal ganglia germinomas and mixed germ cell tumors are associated with ipsilateral cerebral and brainstem hemiatrophy on presentation. Several pathophysiological mechanisms including autoimmune process and direct tumor infiltration of the thalamus or the internal capsule have been postulated to explain this association. Case reports  The authors report two boys, aged 7 and 10, with basal ganglia germ cell tumors. Both of them presented with gradual onset of hemiparesis and had features of ipsilateral cerebral and brainstem hemiatrophy on imaging studies. They underwent chemotherapy followed by reduced dose radiotherapy with good response. Discussion  Pathophysiological mechanisms of the associated ipsilateral cerebral and brainstem hemiatrophy are discussed. The authors postulate that the gradual obliteration of the perforating arteries to the diencephalon especially the lenticulostriate arteries of the prebifurcation middle cerebral artery may be the major mechanism of the associated hemiatrophy.     

bcl-2 protein expression in tumors of the central nervous system

bcl-2 protein (BCL-2) expression was immunohistochemically studied in 140 varied central nervous system tumors. The protein was most frequently expressed in neuronomas and ependymomas, and in normal ependymal cells and Schwann cells. Most pituitary adenomas could be classified into one of two subgroups, diffusely positive or diffusely negative tumors, while BCL-2 localized heterogeneously in normal pituitary glands. Although the protein was not detected in normal astrocytes, it was positive in reactive hypertrophic astrocytes observed in various pathological conditions. Similarly, astrocytic tumor cells often expressed BCL-2. Since lowgrade astrocytomas more often exhibited the protein than malignant gliomas, the degree of BCL-2 expression appeared to be related to the degree of malignancy of the gliomas. On the other hand, 7 out of 17 recurrent gliomas and medulloblastomas showed an increase in the frequency of protein expression compared with specimens from initial treatments. One recurrent astrocytic tumor which demonstrated anaplastic change showed a decrease in the frequency of BCL-2-positive cells. It is concluded that the frequency of BCL-2 expression in CNS tumors is increased when the non-neoplastic counterparts of the tumors exhibit the protein. Although it has been reported that overexpression of BCL-2 protects cells from damage by radiation and/or chemotherapy, we could not find any significant relationship between the degree of BCL-2 expression and the length of survival of patients with glioblastomas or medulloblastomas.     

Diagnostic pitfall in the diagnosis of mesenchymal chondrosarcoma arising in the central nervous system

Mesenchymal chondrosarcoma is a rare aggressive neoplasm typically affecting the bones of young adults. It may also arise in somatic soft tissue, the CNS and other organs. It has a characteristic biphasic histological pattern composed of highly undifferentiated small round cells and islands of well‐differentiated hyaline cartilage. We report a case of mesenchymal chondrosarcoma arising from the right tentorium cerebelli in a 21‐year‐old woman with symptoms relating to mass effect. Histological examination demonstrated a purely small round cell appearance in a specimen obtained during partial resection at an outside institution, leading to an erroneous diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (PNET). The diagnosis of mesenchymal chondrosarcoma was made only after tissue obtained during a definitive complete macroscopic removal involving the regional tentorium cerebelli, transverse and sigmoid dural venous sinuses which showed a prominent cartilaginous component. We discuss the features of mesenchymal chondrosarcoma arising in the CNS, the important differential diagnoses of small round‐cell tumors within the CNS, and the differentiating features of mesenchymal chondrosarcoma from Ewing sarcoma/PNET, medulloblastoma, hemangiopericytoma, monophasic synovial sarcoma and atypical teratoid/rhabdoid tumour.