颅内高度恶性非生殖细胞瘤性生殖细胞肿瘤

目的探讨颅内高度恶性非生殖细胞瘤性生殖细胞肿瘤（non-germinomatous malignant germ cell tumors,NGMGCTs）的临床特点、治疗和预后.方法回顾性分析了19例高度恶性NGMGCTs患者的临床特点、血清肿瘤标记物监测、治疗方法以及预后.其中胚胎癌2例,卵黄囊瘤4例,绒毛膜上皮癌7例,混合性生殖细胞肿瘤6例.有7例术前肿瘤标记物监测均异常,所有患者均行手术切除肿瘤,全切除7例,近全切除10例,大部分切除2例.所有患者均行放疗,有11例行术后化疗.结果共随访到17例患者,平均随访3.5年,1年生存率为29.4%,3年生存率为5.9%.其中卵黄囊瘤1年生存率为25.0%;混合性生殖细胞肿瘤3年生存率为20.0%,胚胎癌和绒毛膜上皮癌患者皆于1年内死亡.结论高度恶性NGMGCTs预后很差.根据临床表现、影像学资料和肿瘤标记物甲胎蛋白（AFP）和（或）β-绒毛膜促性腺激素（β-HCG）增高,多数患者在术前可确诊为高度恶性NGMGCTs.治疗应先采用化疗后放疗,对治疗后肿瘤标记物水平降至正常而影像学上肿瘤仍未完全消失者,可考虑手术切除,术后再行化疗和（或）放疗.治疗结束后注意随诊,如肿瘤标记物再次升高,经影像学证实肿瘤复发,可再行化疗和手术治疗.这样会延长高度恶性NGMGCTs患者的生存期.     

Intracranial germ cell tumors: a retrospective study of 44 children

This 16-year retrospective study review sought to determine the factors influencing prognosis and treatment results of all patients with primary intracranial germ cell tumors treated at our hospital who were younger than 17 years of age at the time of diagnosis. A total of 44 patients were treated during the study period, including 32 males and 12 females with a male:female ratio of 2.67:1. The median age at diagnosis was 12 years and 5 months of age (range = 2-16 years). The 44 intracranial germ cell tumors consisted of 27 pure germinomas (61.4%) and 17 nongerminomatous germ cell tumors, including 10 mixed germ cell tumors (22.7%), three yolk sac tumors (7.8%), two immature teratomas (4.5%), and two choriocarcinomas (4.5%). Univariate analysis of prognostic factors using Kaplan-Meier survival estimates revealed that only histologic tumor type was correlated with outcome (P < 0.005). The projected 5-year overall survival and event-free survival rate of patients with germinomas vs those with intracranial germ cell tumors were 92.6%, 92.6% vs 47.3%, and 42.1%, respectively. Our analysis suggests that radiation involving the spinal axis has limited usefulness in patients with intracranial germ cell tumor, although better results have been obtained for germinomas using radiotherapy in this study.     

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.     

脑边缘系统肿瘤(附91例分析)

目的 探讨边缘系统肿瘤的临床病理特点以及显微手术治疗策略，特别是锁孔手术的可行性及其疗效。方法 对91例脑边缘系统肿瘤的临床特点、手术方法和病理特点进行系统的回顾性分析。对34例肿瘤直径2.5cm中的32例及57例〉5cm中的9例采用锁孔手术．包括改良翼点入路、眶上额下眉弓入路、发际内过中线横切口的锁孔手术；其余均采用传统开颅手术，如翼点入路，额下入路、纵裂入路等。结果 脑边缘系统肿瘤常见于中青年病人；癫痫发作常是首发或惟一的症状。肿瘤全切53例（58．2％），次全切38例（4l、8％）。术后病理结果示低级别胶质瘤79例（86．8％），海绵状血管瘤4例，间变性星形细胞瘤4例，神经胶质增生2例，动静脉畸形1例．胶质肉瘤1例。结论 脑边缘肿瘤以低分级胶质瘤和其他良性肿瘤为主，继发性癫痫发作是其主要临床表现。对部分肿瘤直径〈5cm的病人．应用锁孔手术可获得满意疗效。     

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。     

Multiple intracranial mixed germ cell tumors

A case of sequential occurrence of multiple intracranial mixed germ cell tumors is presented. An 8-year-old boy with a cystic calcified tumor in the basal ganglia and an increased serum α-fetoprotein concentration was initially treated with radiotherapy. Six years later, a tumor composed of embryonal carcinoma and immature teratoma arose from the right temporo-parietal lobe. This tumor was treated successfully with surgery and radiochemotherapy. The possibility of multicentricity or intra-axial metastasis distant from the original site during the long-term course should be considered in treatment for intracranial germ cell tumors. Received: 6 November 1995 Revised: 17 July 1996     

颅内肿瘤的立体定向放射治疗(附79例报告)

目的　探讨立体定向放射治疗颅内肿瘤的方法和疗效。方法　对 79例胶质瘤等 6种颅内肿瘤采用 5～ 10个非共面弧共治疗 3～ 10次 ,3～ 10Gy/次 ,3次 /周 ,总剂量 2 0～ 5 0Gy。术后随访 6～ 2 4个月 ,以CT/MR示肿瘤平均直径变化为主的指标评定疗效。结果　立体定向放射治疗 (SRT)组 79例 ,有效 6 6例 (83 5 % ) ,立体定向放射外科 (SRS)组 73例 ,有效 6 3例 (86 3% ) ,两组比较无显著差异 (P >0 0 5 ) ;术后放疗 (S RT)组 5 7例 ,有效 36例 (6 3 2 % ) ,与SRT组比较有显著差异 (P <0 0 1) ;SRT组无效 13例 (16 5 % ) ,出现并发症 4例 (5 % ) ;SRS对照组并发症 2 1例 (2 8 8% )与SRT组有显著差异 (P<0 0 1) ;S RT组并发症 6例 (10 5 % ) ,与SRT组比较无显著差异 (P >0 0 5 )。结论　SRT可治疗体积较大和位于重要器官的肿瘤。它与外放疗比较 ,可缩短治疗时间 ,提高个别颅内肿瘤的疗效 ;与SRS比较 ,可减少并发症发生率 ;与S RT比较可提高治疗效果     

颅内生殖细胞肿瘤的免疫组织化学研究

目的：探讨各种颅内生殖细胞肿瘤中免疫组织化学染色的诊断意义。方法：对７６例颅内生殖细胞肿瘤进行５种抗体的免疫组织化学染色。结果：胎盘碱性磷酸酶（ＰＬＡＰ）阳性率８２％（６２／７６），绒毛膜促性腺激素（ＨＣＧ）阳性率３０％（２３／７６），胎盘催乳素（ＨＰＬ）仅占５％（４／７６），甲胎蛋白（ＡＦＰ）和妊娠特异性β１糖蛋白（ＳＰ１）在卵黄囊癌中阳性率１００％（５／５）。结论：ＰＬＡＰ可用于生殖细胞肿瘤与其他肿瘤鉴别诊断。ＡＦＰ和ＳＰ１可检出畸胎瘤中不易察觉的卵黄囊癌成分。ＳＰ１阳性可能提示肿瘤恶性程度高，预后差。     

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.     

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。     

Suprasellar/pineal bifocal germ cell tumors

Purpose  

Intracranial germ cell tumors (GCT) arise from embryonal rests of germinal cells. The aim of this report is to analyze a small group of GCT located simultaneously in the suprasellar and pineal regions without seeding either between both tumors or to other places. We named this group as suprasellar/pineal bifocal germ cell tumors (SPBT).     

Latency of intracranial germ cell tumors and diagnosis delay

Background

Intracranial germ cell tumors (GCTs) frequently take an insidious clinical course before diagnosis. To date, clinical latency has been discussed in the context of germinoma in the suprasellar area and basal ganglia.

Objective

In this study, we classified the clinical latency of intracranial GCTs into three categories and described their characteristics in order to understand the full spectrum of the phenomenon.

Methods

In a cohort of 181 patients with intracranial GCTs, 17 patients had a delayed diagnosis of more than 3 months (90 days) from the initial brain magnetic resonance imaging to the definitive GCT diagnosis. Clinical records and radiological data of the patients were reviewed.

Results

The patients with a delayed diagnosis were categorized into three groups according to their tumor location: suprasellar (nine patients), basal ganglia (six patients), and pineal (two patients). Initial symptomatology corresponded with the tumor location: central diabetes insipidus for the suprasellar group, hemiparesis for the basal ganglia group, and precocious puberty for the pineal group. The overall survival of patients with germinoma and delayed diagnosis was significantly shorter than that of patients who were diagnosed within 3 months (P?=?0.002).

Conclusions

Clinical latency and delayed diagnosis are not restricted to germinomas in the suprasellar area and basal ganglia; they are canonical features of intracranial GCTs including pineal non-germinomatous GCTs. Early detection and proactive diagnosis of these tumors are required because diagnosis delay may negatively influence patient survival.     

伴发颅内肿瘤的Maffucci综合征二例报告及文献复习

目的 报告2例伴有颅内病变的Maffucci综合征病例并文献回顾.方法 通过全身体检进行诊断,进行手术治疗切除颅内病变.结果 结合多发海绵状血管瘤和软骨瘤等全身表现,符合Maffucci综合征临床诊断.结论 我们首次报告了中国人群中伴有颅内病变的Maffucci综合征病例,对Maffucci综合征相关基因及临床表现仍待进一步研究.     

Chordomas: a histological and immunohistochemical study of cases with and without recurrent tumors

Chordomas are rare, slow-growing and often recurrent neoplasms being composed of various cell types (physaliferous, epitheloid, chondroid), thus, showing a wide range of histological features. To study the relationship between histological and immunohistochemical pattern and biological behavior according to different cell types, the authors studied 33 specimens of 17 patients with and without recurrent tumors. Additionally, the histological features according to nuclear atypia and mitotic activity of both groups were analyzed and compared with each other. Predominance of one cell type was observed in 19 specimens (10 were composed mainly of physaliferous, 8 of the epitheloid and one of chondroid cell type). In 7 cases, areas of chondroid differentiation were present. MIB proliferation index tended not to be higher in recurrent tumors but in cases with nuclear atypia and nuclear pleomorphism seems to be predictive for recurrency. Immunohistochemically, nearly all cell types (physaliferous, epithelial-like and cells of chondroid differentiation) of both recurrent and non recurrent chordomas stained positive for epithel membrane antigen (EMA), cytokeratins (KL1, AE1/AE3), S100, vimentin and negative for HMB45 and desmin. Positive staining for NSE was observed in 70% of cases, however, the chondroid componente stained negative in every case.     

Intracranial mixed germ cell tumor with syncytiotrophoblastic giant cells and precocious puberty

Summary The effect of the polycations, protamine sulfate and poly-l-lysine, on the blood-retinal barrier of rat retinal vessels were studied by retrograde perfusion through the aorta or by intracarotid perfusion of the polycation followed by the protein tracer, hemoglobin. Protamine sulfate induced swelling of cytoplasmic organelles and diffuse staining of many endothelial cells by tracer molecules which subsequently entered the subendothelial and perivascular areas. Polylysine caused some diffuse staining but no leakage of tracer through the endothelial cell. Occasionally, tracer was found in the interendothelial junction after protamine perfusion. The results indicate that surface charge is important for maintaining membrane integrity of the endothelial cells and that breakdown of the blood-retinal barrier may be due to the cytotoxic effect of protamine on the endothelial cell.Supported by NIH grant EY04831 and Research to Prevent Blindness, Inc.     

Comparative genomic hybridization in pineal germ cell tumors

Fifteen primary pineal germ cell tumors (8 germinomas, 4 mixed teratomas-germinomas, 2 immature teratomas, and 1 yolk sac tumor) and 2 recurrences of the yolk sac tumor were studied by comparative genomic hybridization (CGH). An average of 1.8 chromosomal changes per germinoma (0.5 gains vs 1.3 losses), 5.5 per mixed teratoma-germinoma (3.0 gains vs 2.5 losses), 3.5 per immature teratoma (2.0 gains vs 1.5 losses), and 2.0 in the yolk sac tumor (2 gains vs 0 losses) were found; the first recurrence showed 7 (4 gains vs 3 losses), the second 13 imbalances (8 gains vs 5 losses). The most frequent imbalances were gains on 12p (40%), 8q (27%), and 1q (20%) as well as losses on 13q (47%), 18q (33%), 9q and 11q (20% each). Among germinomas, the most common chromosomal changes were -13q and -18q (38% each), in mixed teratomas-germinomas +8q (100%), +12p (75%), -13q (75%) and -9q (50%). Seven high-level gains were identified: 5 in mixed teratomas-germinomas (+8q: 3 cases, + 12p: 2 cases), 1 each in a germinoma (+2p) and an immature teratoma (+12p). Minimal common regions of over- and underrepresentation were found on +8q11.22-21.1, +12p11.1-12.1, -9q32-qter, -11q23.2-qter, -13q32-qter and -18q22-qter. Our findings suggest, that imbalances in cerebral germ cell tumors affect the same chromosomes as among their extracerebral counterparts, albeit in a considerably lower frequency among cerebral germinomas where +12p does not seem to play a major role.     

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.