Primary frontoparietal lobe convexity germinoma with dural invasion mimics meningioma

Intracranial germinomas are rare and account for only 0.4-3.4% of primary intracranial tumors. They develop mainly in the midline structures in adolescents. The pineal gland is the most common site of this tumor. Here, we describe an unusual case of a giant primary intracranial germinoma located in the intracranial hemisphere with radiological findings that mimicked a meningioma. The clinical diagnosis of the intracranial germinoma was difficult because of its unusual clinical presentation, the location of the lesion, and atypical imaging findings. Based on this case study, we suggest that germinoma might be a possible diagnosis when a tumor of the hemispheres with dura invasion mimics meningioma, especially in young patients. Furthermore, we recommend that frozen biopsy sections should be taken routinely during surgery to aid in rapid diagnosis and effective therapy.     

Intracranial germ cell tumors: pathobiological and immunohistochemical aspects of 70 cases

Seventy cases of histologically verified intracranial germ cell tumor were reviewed: 43 germinomas, 16 immature teratomas, seven mature teratomas, two embryonal carcinomas, one choriocarcinoma, and one yolk sac tumor. The male-to-female ratio was 2.6:1. The average age was 19 years in patients with germinoma, 11 years in patients with immature teratoma, and 17 years in patients with mature teratoma. Duration of symptoms averaged 19 months for germinoma, three months for immature teratoma, and 11 months for mature teratoma. Sixty-six lesions were located in the midline. Fifty-eight percent of the germinomas arose anterior to the pineal gland, whereas 29% of the immature and 14% of the mature teratomas were located anteriorly. The histologic appearance of the germinomas was indistinguishable from that of the usual testicular seminoma. The immature teratomas contained tissue from all three germ layers and exhibited morphologic features of fetal tissue. Of 14 immature teratomas, seven contained, in addition, foci of other malignant germ cell elements; thus, there were two teratocarcinomas, two lesions with germinoma and immature teratoma, two lesions with extensive rhabdomyoblastic differentiation in an immature teratoma, and one lesion with both germinoma and embryonal carcinoma in addition to immature teratoma. The seven mature teratomas consisted of fully differentiated epithelial and mesenchymal tissues. In 23 cases, immunoperoxidase stains for human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP), and carcino-embryonic antigen (CEA) revealed patterns which, with minor exceptions, were essentially identical to those found in genital germ cell lesions. Survival was longest for patients with germinomas. In classifying germ cell tumors of the central nervous system, the World Health Organization's (WHO) classification of testicular germ cell tumors is preferable to its present classification of intracranial germ cell tumors.     

Germinoma with synchronous involvement of midline and off-midline structures associated with progressive hemiparesis and hemiatrophy in a young adult

Introduction Cerebral germinomas, the most common and least malignant intracranial germ cell tumors, usually arise in the pineal or suprasellar region and have characteristic clinical and radiological features. Germinomas more rarely occur in the thalamus, basal ganglia, and internal capsule, causing sometimes cerebral hemiatrophy and hemiparesis. More rarely, other clinical features can be fever of unknown origin, visual disturbance, and neuropsychiatric symptoms. Cerebral hemiatrophy can precede the imaging depiction of the off-midline mass. Case The authors present the first case of cerebral germinoma with synchronous involvement of the midline and off-midline structures, with unusual clinical and radiological presentation. Discussion The literature is reviewed, and the pathogenesis, the clinical findings, the imaging, and the therapy are discussed.     

Germinoma involving the basal ganglia in children

Background Germinoma originating in the basal ganglia is rare, and the majority of reported papers have been from Japan. In a collection of the first 500 cases of primary brain tumors in children in Taipei Veterans General Hospital, six pure germinomas with tissue diagnosis situated in this location. Materials and methods We reviewed the clinical features, neuroimaging studies, tumor markers, management, and outcome of these six patients. Results All of them were boys. The median age of onset of symptoms was 9.7 years. They uniformly presented with hemiparesis. The average duration of symptoms before surgical management was 1 year. One patient had bilateral basal ganglia tumors. Serum β-human chorionic gonadotropin levels was elevated (128 mIU/ml) in one patient. Longitudinal neuroimaging studies in four patients clearly showed that the tumor arose as a tiny lesion at the lenticular nucleus. Five patients had cysts within tumors. Five patients received partial, subtotal, to total resection. One patient had stereotactic biopsy of the tumors. Postoperative primary adjuvant therapies included radiotherapy, chemotherapy alone, and combined chemotherapy and radiotherapy. Five patients survived, and one patient died of radiation-induced sarcoma with median follow-up period of 13.7 years. Local recurrence was observed in all of three patients after solitary postoperative chemotherapy. Conclusions The lenticular nucleus is a significant locus for germinomas and can be bilateral. Although rarely reported in Western countries, it does exist in Taiwan as well. Treatment of germinomas in this specific location is similar to germinoma in other intracranial locations.     

Germinoma of medulla

Germinoma occurring in the medulla oblongata is extremely rare. We report a case of primary intracranial germinoma arising in the medulla oblongata of a 24-year-old postpartum female who presented with progressive weakness of upper and lower limbs, seventh nerve palsy, and decreased palatal movements. Her MR imaging showed a heterointense mass lesion in the posterior portion of upper medulla, the histology of which was reported as germinoma. Germ cell tumors should be considered in the differential diagnosis of tumors occurring in the brain stem.     

Intracranial optic nerve germinoma.

A 11-year-old boy presented with complaints of diminution of vision in the left eye for three months. On examination, the vision in this eye was reduced to only perception of light. Magnetic resonance imaging revealed a thickened left intracranial optic nerve. The lesion was explored by a pterional craniotomy. At surgery, the left optic nerve was diffusely thickened. The biopsy of a fleshy mass along the optic nerve showed that it was a germinoma on histopathology. Isolated optic nerve germinomas are extremely rare. Exclusive primary involvement of the intracranial portion of the optic nerve by a germinoma has not been reported in the literature. This rare case is discussed and the relevant literature has been reviewed.     

Central nervous system germinomas. A review

The germinoma represents a less malignant form of germ cell tumor. Depending on the individual's age, this neoplasm constitutes approximately 0.1% to 3.4% of all intracranial tumors. The embryologic origin remains a mystery; however, current theories implicate an aberration in primordial germ cell migration. Clinical presentation depends on tumor location and may involve endocrine, hypothalamic, visual, and cognitive dysfunction. In evaluating midline intracerebral masses, it is imperative that one be aware of the various radiologic appearances, endocrinologic changes, and chemical markers that help to distinguish germinomas from other neoplasms that appear in the pineal, suprasellar, and periventricular regions. Only through the careful evaluation of all available studies can the physician institute appropriate therapies such as biopsy, radiation, and chemotherapy. This article focuses on the epidemiology, embryology, clinical presentation, means of diagnosis, treatment, and outcome of this rare neoplasm.     

Histochemistry with Helix pomatia agglutinin in human germ cell tumors: detection of nongerminomatous components and correlation between HPA reactivity and radiosensitivity in germinomas

Binding sites of Helix pomatia agglutinin (HPA) were examined in 32 patients with intracranial human germ cell tumors. HPA reactivity was found in vascular endothelial cells and erythrocytes of patients with blood type A or AB. HPA-positive neoplastic cells were seen in one yolk sac carcinoma in a patient with blood group. A, and in embryonal carcinomas and teratomas irrespective of blood group type. Although in 10 out of 18 germinomas neoplastic cells were totally negative for HPA, another 8 germinomas showed HPA-positive neoplastic cells which were distributed sporadically or in an area and independent of blood group types. HPA-negative germinoma patients showed a very good response to radiotherapy, whereas 4 out of 8 HPA-positive tumors showed poor radiosensitivity, with a residual lesion seen on computed tomography even after the total radiation dose of 40–50 Gy. These findings suggest that HPA-positive neoplastic cells in germinomas indicate components of differentiation of non-germinomatous germ cells. HPA-positive germinomas might be less radiosensitive than HPA-negative germinomas.     

Multiple germinomas due to early intracranial metastasis.

A case with multiple intracranial germinomas involving basal ganglia and corpus callosum is presented. Clinical and sequential neuroradiological studies demonstrated the entire course of multiple tumour development. These findings suggested that the multiple tumours were intracranial metastatic deposits from primary germinoma in the pineal body. A common primary pineal or suprasellar lesion should be carefully ruled out in the cases of germ cell tumours occurring in unusual regions.     

颅内生殖细胞瘤的临床治疗探讨

目的：探讨颅内生殖细胞瘤的综合治疗方法。方法临床诊断颅内生殖细胞瘤１３例，其中孤立型８例，侵袭型４例，播散型１例；治疗上对孤立型采取局灶放疗同时联合顺铂、足叶乙甙化疗，侵袭型与播散型加用氨甲喋呤脑或鞘注给药化疗。结果肿瘤完全消失１１例，瘤体缩小９０％以上２例，随访０．３－４．５年（平均２．７年），无１例复发，全部病例生存状况良好。结论治疗上针对肿瘤的临床分型，采取局灶放疗与不同的化疗方案联合能有效     

脑脊液细胞学在脑生殖细胞瘤诊断中的应用及八例报告

目的 通过总结8例脑生殖细胞瘤患者的脑脊液细胞学结果,探讨脑脊液细胞学在脑生殖细胞瘤诊断中的价值.方法 总结2006年1月至2009年6月我院脑脊液细胞学发现肿瘤细胞的8例脑生殖细胞瘤患者,分析其临床特点、影像学和脑脊液细胞学结果.结果 8例患者中男性7例,女性1例.年龄13～25岁,分别以多饮、多尿和少汗等内分泌症状或神经科症状起病.神经科症状包括:头晕、头痛、智能减退、精神行为异常、复视、双下肢无力、尿便障碍等.神经影像学可见鞍上区和(或)松果体区占位、脑室扩张、室管膜和软脑膜强化、神经根增粗强化等.脑脊液绒毛膜促性腺激素3.2～1087.0 mIU/ml.脑脊液细胞学8例均见肿瘤细胞,呈中等大小的圆形,核大,核仁明显,胞质丰富,胞质内可见较多空泡.背景间有小淋巴细胞为主的炎性反应.过碘酸Schiff染色肿瘤细胞胞质中见阳性颗粒.4例行免疫细胞化学染色,其中2例抗胎盘碱性磷酸酶阳性;2例行Ki-67染色,阳性细胞分别占12%和20%.细胞角蛋白和癌胚抗原染色等阴性.结论 脑生殖细胞瘤患者的脑脊液细胞学结果特征明显,结合细胞免疫化学可以明确其类型及脑脊液播散,在诊断脑生殖细胞瘤过程中起着重要作用.

Abstract：

Objective To investigate the value of the cerebrospinal fluid ( CSF ) cytology in diagnosis of intracranial germinomas by reviewing the outcomes of CSF cytology of 8 patients with intracranial germinomas. Methods Eight patients with positive CSF cytology at our clinic from January 2006 to June 2009 were reviewed. Conventional cytology and immunocytochemistry of CSF were performed. The relevant literature on the subject was reviewed. Results The patients, including 7 male and 1 female, developed endocrinological or neurological symptoms at the age of 13 to 25, and the typical neurological presentation included vertigo, headache, mental and behavior disorders, double vision and weakness of legs. The CSF cell count ranged from 0 to 300 leukocytes per cubic and elevated in 7 cases, typically lymphocytic inflammation. CSF level of human chorionic gonadotropin was 3.2-1087.0 mIU/ml, higher than the individual serum level. On CSF cytology studies, typical tumor cells of germinima were found, which had positive particles in cytoplasm on periodic acid Schiff stain. All presents had lymphocyte inflammation ( small lymphocyte predominant ). On immunocytochemical studies of CSF, the tumor cells were positive on placental alkaline phosphatase and Ki-67 stains. Conclusions CSF cytology is clinically useful for diagnosis of primary intracranial germinoma. Further clinical and cytological studies will be necessary for a better understanding of the biology of these tumors.     

化、放疗联合治疗儿童颅内生殖细胞瘤34例临床随诊观察

目的：观察颅内生殖细胞瘤经过化疗并辅以中低剂量放疗后的疗效及对儿童生长发育的影响。方法：自1993年12月至2001年12月共对63例颅内生殖细胞瘤的儿童进行静脉化疗并辅以中低剂量放疗，随访到34例，其中肿瘤位于松果体区20你，松果体区并鞍区6例，鞍区4例，松果体区并脑室内3例，底节区1例。使用药物为长春新碱、甲氨蝶呤、平阳霉素及顺铂。用药后每周化验2次血常规，1次血生化，以观察周围血象变化及心、肝、肾功能情况，并进行针对性治疗。4周后如血常规及血生化的各项指标均正常，再行第二疗程化疗。2个疗程结束后1个月，在肿瘤病灶局部补充中低剂量（25-35Gy）的放疗。每个疗程间进行CT或MRI检查，观察肿瘤消退的情况。：34例患者随访最短1年，最长7年。1例为手术加全剂量放疗后2年肿瘤复发，此次化疗进行2个疗程，但化疗后未再补充放疗，4年后肿瘤复发，家属放弃治疗，患者死亡。1例化、放疗后5年肿瘤复发，再行2疗程化疗，疗效较首次治疗差，其余32例（94％）化、放疗后1-7年，复查MRI显示肿瘤无复发，患者生存质量良好，儿童生长发育及智力均未受影响。结论：静脉化疗辅以中低剂量放疗应为治疗儿童颅内生殖细胞瘤的最佳方案。     

Human chorionic gonadotrophin in CSF, not serum, predicts outcome in germinoma

OBJECTIVES: Some intracranial germinomas, which may contain syncytiotrophoblastic giant cells (STGCs), are associated with a mildly to moderately increased human chorionic gonadotropin (HCG) concentration in serum, and patients with such germinomas are thus treated more aggressively than those with "pure" germinoma. However, the patients with germinoma and detectable HCG in CSF but not in serum have been classified and treated similarly to those with "pure" germinomas. The outcome of these patients and the relevance of HCG in the CSF were analysed. METHODS: The outcomes of patients with germinoma and increased serum HCG concentration (n=7) were compared with those of patients having detectable HCG titre in the CSF but not in the serum (n=5). RESULTS: Both groups in our series received similar treatments and also showed similar recurrence rates. The 40% recurrence rate in the group with HCG only in CSF did not correspond to the rate typical for "pure" germinoma: these tumours would be expected to have a better outcome. An additional patient whose CSF HCG were raised without increased serum HCG at recurrence is presented. CONCLUSIONS: It is recommended that patients with an increased HCG concentration in CSF should be considered to have "HCG producing germinoma", and they should be treated and followed up accordingly.     

Suprasellar germinoma in three lake whitefish (Coregonus clupeaformis)

Suprasellar germinomas were identified in three wild-caught lake whitefish (Coregonus clupeaformis) from the St. Lawrence River, Quebec, Canada. Histologically, the three tumors expanded the subarachnoid space of the ventral surface of the brain immediately adjacent to the pituitary gland and, in one case, infiltrated the adjacent neuropil. These tumors were characterized by nests and sheets of round cells with a high mitotic rate, separated by a scant amount of loose fibrovascular stroma. The stroma was infiltrated by a moderate number of small mononuclear cells, including rare CD3-immunoreactive lymphocytes. This is the first report of intracranial germinoma in a fish species. Received: 13 July 1999 / Revised, accepted: 15 November 1999     

Intracranial germinomas in a father and his son

Background

Primary intracranial germ cell tumors (IGCTs) represent an uncommon category of neoplasms, and familial occurrence is rare. We present the first report of parent-child patients with pathologically confirmed pure germinomas.

Case report

A 36-year-old Japanese man presented with diabetes insipidus and hypopituitarism. Magnetic resonance imaging (MRI) revealed a mass lesion in the pituitary stalk, which was diagnosed as a pure germinoma by open craniotomy tumor biopsy. Seven years later, his 13-year-old son also presented with diabetes insipidus. MRI revealed mass lesions in the pituitary stalk and the pineal region. He underwent endoscopic tumor biopsy for the pineal lesion, which was diagnosed as a pure germinoma. Both the father and his son were treated with combined radiochemotherapeutic regimens and achieved complete remission after one to two cycles of chemotherapy.

Conclusion

Although there have been three previous case reports of familial germinoma, all of these involved sibling pairs. The present report represents the first parent-child cases. This type of familial occurrence suggests the possibility that germline mutations may also be involved in the development of IGCTs.     

Delayed resolution of intracranial germinoma after radiotherapy: A preliminary study of the correlation between histology and magnetic resonance imaging

A central nervous system germinoma is curable in most cases by radiotherapy, and most of the tumor mass disappears promptly after 20–30 doses. However, some germinomas take a longer period to vanish completely from magnetic resonance imaging (MRI) or computed tomography (CT) scans. In such cases, the tumor may contain components such as teratoma. The aim of this study was to clarify the nature of the persistence of some germinomas. Five cases of histologically verified germinoma in which radiotherapy was performed to treat residual tumor were selected. The doses of focal radiotherapy and whole brain radiotherapy were 10–20 Gy and 20–34 Gy, respectively. In these cases, correlation was made between the degree of persistence of the tumor when assessed by MRI and the amount of interstitial content, as determined by histology. The histological evaluation, using hematoxylin–eosin stain, silver impregnation and Azan staining was carried out independently of clinical information. The tumor vanished soon after radiotherapy in three cases, but 3–15 months passed before the tumor completely vanished from the MRI scans in the other two cases. The histology of the cases in which the tumor disappeared rapidly was predominantly of large tumor cells and only small amounts of reticulin. However, in the persistent tumors, large amounts of reticulin and vascular components were present. Thus, it is proposed that tumors with a large parenchymal component disappear soon after radiotherapy, whereas tumors composed mainly of interstitial component persist. Long‐standing enhancement seen on MRI or CT scans of patients with an intracranial germinoma is indicative of a large amount of interstitial component in the tumor.     

Treatment strategy for intracranial primary pure germinoma

Object

This prospective randomized clinical study will address the efficacy of radiation (RT)-alone and combined with pre-RT chemotherapy (CTX) treatments and propose the novel standard treatment strategy for intracranial primary pure germinoma.

Materials and methods

Between 2005 and 2008, there were 54 patients diagnosed with intracranial primary pure germinomas in a single institute. Twenty-eight patients were enrolled. The mean age of the patients was 16.2 years (range 6–31 years). There were 19 men and 9 women (men/women ratio?=?2.1:1). There were 21 patients with solitary tumors and 7 with multiple tumors. These patients were randomized as RT-only treatment group (11 solitary and 3 multiple tumors) and combined (10 solitary and 4 multiple tumors, neo-adjuvant CTX followed by response-adapted RT) treatment group. The follow-up period for RT only group has a median of 58 months (mean 58.2 months, range 41–82 months), and for combine therapy group, the median was 68.5 months (mean 67.8 months, range 41–88 months). All 14 patients in the RT-only group showed complete response (CR) and no recurrence. Eleven patients in the combined group had CR and three patients had partial response after neo-adjuvant CTX. All patients responded to RT as CR without recurrence. At the time of analysis, all 28 patients were alive without evidence of disease.

Conclusion

Neo-adjuvant CTX for localized germinomas seems to be unnecessary as a method to reduce radiation dose in our RT protocol. However, the effective control of multifocal or disseminated germinoma can be achieved by neo-adjuvant CTX followed by response-adapted reduced dose RT.     

颅内成熟畸胎瘤全切除术后远期再发2例及文献复习

目的探讨颅内成熟畸胎瘤全切除后远期再发颅内肿瘤的性质及其发病机制。方法报告2例颅内成熟畸胎瘤病人．分别于全切除术后21个月、8年再次发生颅内肿瘤,均行2次手术治疗。结果影像学资料显示再发肿瘤部位与首发肿瘤有差异,术后病理分别为生殖细胞瘤、恶性畸胎瘤。结论颅内成熟畸胎瘤全切除术后远期再发不同部位的颅内肿瘤应首先考虑为新生的异时性肿瘤,多为恶性生殖细胞肿瘤,尤以生殖细胞瘤为著。     

Understanding the Treatment Strategies of Intracranial Germ Cell Tumors: Focusing on Radiotherapy

Intracranial germ cell tumors (ICGCT) occur in 2-11% of children with brain tumors between 0-19 years of age. For treatment of germinoma, relatively low radiation doses with or without chemotherapy show excellent 10 year survival rate of 80-100%. Past studies showed that neoadjuvant chemotherapy combined with focal radiotherapy resulted in unacceptably high rates of periventricular tumor recurrence. The use of generous radiation volume which covers the whole ventricular space with later boost treatment to primary site is considered as standard treatment of intracranial germinomas. For non-germinomatous germ cell tumors (NGGCT), 10-year overall survival rate is still much inferior than that of intracranial germinoma despite intensive chemotherapy and high-dose radiotherapy. Craniospinal radiotherapy combined with cisplatin-based chemotherapy provides the best treatment outcome for NGGCT; 60-70% of overall survival rate. There is a debate on the surgical role whether surgery can contribute to improved treatment outcome of NGGCT when added to combined chemoradiotherapy. Because higher dose of radiotherapy is required for treatment of NGGCT than for germinoma, it is tested whether whole ventricular irradiation can replace craniospinal irradiation in intermediate risk group of NGGCT to minimize radiation-related late toxicity in the recent studies. To minimize the treatment-related neural deficit and late sequelae while maintaining long-term survival rate of ICGCT patients, optimized administration of chemotherapy and radiotherapy should be selected. Use of technically upgraded radiotherapy modalities such as intensity-modulated radiotherapy or proton beam therapy is expected to bring an improved neurocognitive outcome with longitudinal assessment of the patients.     

Cerebral germinoma with marked granulomatous inflammation: Granulomatous germinoma

Cerebral germinomas with granulomatous inflammation are rare lesions that can present diagnostic difficulties. Four cases (two male and two female) of germinomas with pronounced inflammatory reaction are presented. The age ranged from 14 to 21 years (mean 18). Three patients with vision defects had masses around the sellar region, and a long duration of symptoms (2, 4 and 5 years). The fourth patient had a mass in the temporal lobe; she had convulsions and the duration of her symptoms was short (3 weeks). All lesions consisted of inflammatory changes with scattered neoplastic germinoma cells that expressed placental alkaline phosphatase. The inflammation area occupied more than two-thirds of the mass, and consisted of macrophages and their syncytial forms of mutinucleated giant cells, T-cells, B-cells, plasma cells, fibroblasts, and histiocytes or glial cells. Sarcoid granulomata were frequently seen, and multinucleated giant cells with Schaumann's bodies were also visible. The term ‘cerebral granulomatous germinoma’ is proposed for these unusual tumors. Moreover, it is likely that the study of cerebral granulomatous germinoma may provide some important clues towards the understanding of granulomatous inflammation in organs in general.