低剂量诊断性放疗联合化疗在诊治颅内生殖细胞肿瘤中的价值

背景与目的：颅内生殖细胞肿瘤（intracranial germ cell tumors）经积极放化疗常可获得令人满意的局部控制率和生存率，然而对部分无法取得病理诊断的颅内生殖细胞肿瘤的治疗，研究者们至今无法达成一致意见。该研究探讨低剂量诊断性放疗联合化疗在诊治颅内生殖细胞肿瘤的可行性及临床意义。方法：该研究分析了贵州省人民医院及北京天坛医院收治的28例（16例男性，12例女性，中位年龄14.5岁）高度怀疑为颅内生殖细胞肿瘤的患者。患者血浆和（或）脑脊液人绒毛膜促性腺激素（β-human chorionic gonadotropin，β-HCG）和甲胎蛋白（α-fetoprotein，AFP）均为阴性，头颅MRI诊断提示鞍区和（或）松果体区呈典型生殖细胞肿瘤影像特征，临床表现高度提示可能为生殖细胞瘤（germinoma）。这些患者因无法通过手术及立体定向活检明确病理诊断，或患者本身不同意手术或活检，因此我们建议实施诊断性低剂量放疗联合化疗方案，诊断性放疗剂量为3.4 Gy，1.7 Gy/2次。经低剂量诊断性放疗后行MRI复查。随后根据MRI复查结果采用以下治疗：⑴ 影像学为进展（progression disease，PD）或稳定（stable disease，SD），建议手术治疗。⑵ 影像学达完全缓解（complete response，CR）或部分缓解（partial release，PR），再予以2个周期化疗，顺铂+足叶乙甙（DDP+VP16）方案2个周期，化疗后再次行MRI复查，如果患者影像学检测结果显示达CR，随即按生殖细胞瘤进行调强放疗（intensity-modulated radiation therapy，IMRT）及三维适形放疗（three-dimensional conformal radiotherapy，3D-CRT)。放疗方案根据患者情况进行选择：① 局部放疗；② 全脑全脊髓+局部加量放疗；③ 全脑+局部加量放疗（松果体区病变总剂量小于等于50.4 Gy；鞍区病变总剂量小于等于41.0 Gy）。⑶ 经低剂量诊断性放疗联合化疗后行MRI复查，如果患者影像学仍未达CR，建议患者立即接受手术治疗。参考WHO实体瘤疗效评价标准判断放化疗效果。结果：经诊断性放疗后显示为SD的患者1例，被随后的手术证实为垂体瘤。经低剂量诊断性放化疗后，病灶影像学诊断结果显示26例达CR，考虑临床诊断为颅内生殖细胞肿瘤，随即予患者行IMRT及3D-CRT；治疗后影像学复查均为CR，以上患者随访时间1~8年，所有患者均无瘤生存，无复发，未见放射性坏死。经诊断性放疗及2个周期化疗后仍有1例患者影像学诊断结果显示未达到CR，后经手术证实为混合性生殖细胞肿瘤。结论：低剂量诊断性放疗联合化疗具备区分颅内生殖细胞瘤与非生殖细胞瘤的能力，对高度怀疑为颅内生殖细胞肿瘤的患者, 在没有病理证实的情况下，可参考此方案进行诊断性治疗和临床处理。     

颅内非松果体区生殖细胞瘤10例临床分析

目的:分析颅内非松果体区生殖细胞瘤临床表现、检查、诊断和治疗的特点.方法:对我院1993-2007年收治的10例颅内非松果体区生殖细胞瘤进行回顾性分析.结果:男性7例,女性3例;发病部位:鞍区8例,基底节区2例.经手术或脑组织活检病理诊断确诊5例,经诊断性放疗拟诊5例.5例行肿瘤部分或全部切除术;5例行放疗,其中3例联合化疗,症状均有不同程度缓解.结论:颅内生殖细胞瘤多发于青少年,男性多于女性,放射治疗是有效的治疗方法,压迫症状明显患者可行手术治疗.     

松果体区肿瘤的显微手术治疗：21例经验

背景与目的：松果体区肿瘤治疗目前仍存在争议,为此我们进一步探讨松果体区肿瘤的临床特点及显微手术治疗。方法：回顾性分析2002。2008年收治的21例松果体区肿瘤患者的临床资料。结果：肿瘤全切除15例,次全切除4例,部分切除2例。21例的手术病理结果中,生殖细胞瘤9例、松果体母细胞瘤5例、胶质瘤2例及其他肿瘤5例。结论：松果体区肿瘤的诊断须以病理组织学分类为依据．松果体区静脉系统是阻碍手术操作的主要结构．显微外科手术应可良好地保护此区静脉．是松果体区肿瘤全切除的关键所在。     

肝胆管囊腺瘤诊治临床探讨

目的 探讨肝胆管囊腺瘤的临床特点、诊断方法和治疗措施.方法 回顾分析2002年1月至2009年12月收治的12例肝胆管囊腺瘤患者的临床资料.结果 肝胆管囊腺瘤临床表现缺乏特异性,12例患者4例误诊为肝囊肿,8例行B超引导下细针穿刺活检,结合影像学检查诊断为肝胆管囊腺瘤,术后病理确诊.全部患者行肿瘤标记物检查未见异常.2例患者总胆红素水平轻度升高.12例患者全部行切除术,随访至今未见复发.结论 肝胆管囊腺瘤临床缺乏特异性表现,血清学检查价值有限,影像学结合细针穿刺活检有助于诊断,手术切除疗效确切,是本病的最佳治疗方法.     

松果体区肿瘤的临床病理研究

目的研究松果体区肿瘤（PRTs）的病理分布特点及不同病理类型的临床特点。方法回顾性分析南方医院神经外科自2000年1月至2009年1月经手术治疗并取得完整病理资料的133例PRTs患者的临床资料及病理特点．结果133例患者中生殖细胞肿瘤61例（45．9％）,松果体实质肿瘤17例（12．8％）,神经上皮肿瘤28例（21．1％）,其他肿瘤27例（20．2％）。生殖细胞肿瘤中男女比例为14．25：1,平均15．3岁。松果体实质肿瘤中男女比例为2．4：1,平均24．7岁。神经上皮肿瘤中男女比例为1．15：1,平均28．1岁。有33例血清免疫学检查异常,除1例为转移瘤外,其余均为生殖细胞肿瘤。结论PRTs病理类型多样,以生殖细胞肿瘤为主;影像学检查、血清免疫学检查及活检均不能准确判断病理类型,积极手术获得完整病理标本对于PRTs的病理研究有重要意义。     

颅内非松果体区生殖细胞瘤10例临床分析

目的：分析颅内非松果体区生殖细胞瘤临床表现、检查、诊断和治疗的特点。方法：对我院1993—2007年收治的10例颅内非松果体区生殖细胞瘤进行回顾性分析。结果：男性7例,女性3例;发病部位：鞍区8例,基底节区2例。经手术或脑组织活检病理诊断确诊5例,经诊断性放疗拟诊5例。5例行肿瘤部分或全部切除术;5例行放疗,其中3例联合化疗,症状均有不同程度缓解。结论：颅内生殖细胞瘤多发于青少年,男性多于女性,放射治疗是有效的治疗方法,压迫症状明显患者可行手术治疗。     

松果体区肿瘤的争论及其治疗策略

松果体区肿瘤病理类型多样、术前定性诊断困难、多数对单纯放疗的疗效并不理想,随着现代显微神经外科技术和安全性的提高,诊断性放疗应该放弃。其最佳治疗方法目前仍存在争论。准确的病理诊断是提高松果体区肿瘤疗效所必须的。活检在松果体区肿瘤诊断中的价值及其安全性在文献中被错误的估计。近年来,松果体区肿瘤手术全切除率越来越高,死亡率和并发症发生率已显著降低至可接受的水平。由于多数松果体区肿瘤如能达到全切除,再根据准确的病理结果辅以必要的术后辅助治疗,可以改善预后,因此松果体区肿瘤应采用以积极手术为主的综合治疗方法。     

膝关节滑膜源性肿瘤的临床特征、诊断和治疗

目的 研究膝关节滑膜源性肿瘤的临床特征,探讨并分析滑膜肿瘤的临床表现并提出鉴别诊断及治疗方法.方法 回顾我院从2005年至2009年收治的38例经病理证实为膝关节滑膜源性肿瘤患者的诊断、治疗及随访观察,分析各类型滑膜肿瘤病变的临床表现、影像学的特点及手术方法,并观察各类型滑膜病变的不同病理特征.结果 膝关节滑膜源性肿瘤好发于各个年龄段,38例患者包括色素沉着绒毛结节性滑膜炎,滑膜软骨瘤病,滑膜血管瘤,滑膜肉瘤,滑膜脂肪瘤,术后得到随访的31例患者中(平均随访时间28.4个月),色素沉着绒毛结节性滑膜炎复发4例(22%),滑膜软骨瘤病1例(17%),滑膜肉瘤1例(50%),膝关节功能总体优良率为83.9%.结论 膝关节滑膜源性肿瘤病种复杂,易误诊误治,应通过详细地询问病史,仔细对患者做体格检查,配合实验室及影像学检查,采用切开直视的手术方法减少误诊率并提高治疗效果.     

肾原始神经外胚层肿瘤2例报告

肾原始神经外胚层肿瘤（primitive neuroeetodermal tumor，PNET）临床罕见。肾PNET临床表现及影像学检查均缺乏特异性。术前大多诊断为肾细胞癌，术后病理学检查才得到明确诊断。肾PNET在治疗上与肾细胞癌不同，采取包括手术、联合化疗和放疗在内的综合治疗。而肾细胞癌对放化疗不敏感，主要采取手术和生物治疗。我们报道2例肾PNET．并对相关文献进行每习．     

松果体母细胞瘤1例并文献复习

松果体母细胞瘤是罕见的颅内肿瘤,约占松果体实质细胞肿瘤的45％,几乎和松果体细胞瘤各占一半,可见于各年龄段,但多见于20岁以前,好发于儿童,男性略占多数。临床表现多种多样,可表现为颅内压增高,眼神经障碍,精神异常等,临床上与松果体区生殖细胞肿瘤难以鉴别。笔者报道1例松果体母细胞瘤,结合文献对其进行光镜、免疫组化研究,讨论其临床病理特征及诊断与鉴别诊断。     

神经内镜在合并梗阻性脑积水的松果体区肿瘤诊治中的应用

背景与目的：松果体区肿瘤的位置深在,毗邻重要的结构,病理类型丰富,故其诊断及治疗一直是神经外科最富挑战和争议的领域。本研究总结应用神经内镜治疗合并梗阻性脑积水的松果体区肿瘤的疗效,评价神经内镜在诊治过程中的作用。方法：对53例合并梗阻性脑积水的松果体区肿瘤患者应用神经内镜行第三脑室底造瘘加肿瘤活检术,在解决脑积水同时明确肿瘤病理性质,其后给予综合治疗。结果：本组病例术后梗阻性脑积水均解除,51例获病理结果。结论：在合并梗阻性脑积水的松果体区肿瘤的初期治疗中,神经内镜是一种有效的诊疗手段．     

Pineocytomas of childhood. A reappraisal of natural history and response to therapy

Pineocytomas are pineal parenchymal tumors composed of differentiated cells histologically similar to those of the mature pineal gland. Little is known about the incidence, pattern of growth, or response to treatment of pineocytomas. Between 1975 and 1985, six children with pineocytomas were treated at our institution, and pineocytomas constituted 11% of all newly diagnosed pineal region tumors. The clinical, radiographic, and pathologic features of these six patients with pineocytomas are presented. Initial treatment for these children included craniospinal plus supplemental local radiotherapy (three), local radiotherapy alone (one), or radiation therapy plus adjuvant chemotherapy (two). Four of six patients had tumor recurrence a median of two years after diagnosis. Three patients had leptomeningeal dissemination, one at the time of diagnosis and two following therapy. Our findings suggest that: biopsy is necessary to distinguish pineocytomas from other pineal region tumors; radiation therapy alone is inadequate; and these tumors are aggressive in the pediatric population, with a high propensity for leptomeningeal dissemination.     

脾脏肿瘤31例临床分析

目的 通过临床病例分析,了解脾脏肿瘤的临床特点。方法 对1990年1月－2000年12月期间收治的31例脾脏肿瘤患者的临床表现、影像学特点和诊断依据、治疗情况进行了分析。结果 31例脾脏肿瘤中良性肿瘤居多（20／31）。临床表现无特异性。影像学特点为脾实质内单发或多发结节。全部患者均是先行B超检查发现脾脏占位,其中19例又行CT检查,7例行MRI检查。7例脾囊肿通过B超等影像学检查明确诊断,其中6例在手术后病理证实;9例脾脏转移性肿瘤通过影像学检查并结合病史在术前明确诊断,有5例经手术切除后病理证实;另外15例脾脏病变,除1例因术前CT检查明确为脾脏淋巴管瘤而放弃手术外,其余14例则以脾脏肿瘤而行脾脏切除手术,术后病理明确诊断。全组31例患者中,25例行脾切除术,术后恢复均较顺利,无手术死亡。结论 病史和影像学检查是诊断脾脏肿瘤的重要依据,术前不易鉴别良恶性肿瘤,手术效果佳。     

Neuroendoscopic anatomy and surgery in pineal region tumors

The therapeutic modalities for pineal region tumors in Western countries differ from those in far-eastern countries, that is, Japan and Korea, mainly because of the different patient populations. The majority of pineal region tumors in Japan and Korea are radio sensitive and/or chemosensitive, and adjuvant therapy rather than extensive surgery plays the main part in the treatment of these tumors. The authors have applied minimally-invasive preferential management in pineal region tumors in last 8 years. For the therapeutic regimen, if the tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were not detected in serum and there was significant ventricular dilation visualized on neuroimages, neuroendoscopic surgery was first applied for tumor debulking with tissue diagnosis and gross morphological analysis of the tumor and the intraventricular structures, followed by third-ventriculostomy. In the results, our minimally-invasive preferential regimen clarified the precise indication for neuroendoscopic procedures, and the majority of our patients with dilated ventricles and no evidence of tumor markers were treated satisfactorily with effective neuroendoscopic procedures as the initial procedure. Then avoided unnecessary craniotomy and radiotherapy and promised excellent therapeutic outcomes. Neuroendoscopic procedures have a great advantage in the management of chemo- or radiosensitive tumors, such as germinoma, pineoblastoma, or primitive neuroectodermal tumor. The neuroendoscopic anatomy including the lateral and third ventricles with a pineal region tumor with or without tumor dissemination was described in detail, together with the neuroendoscopic surgical technique.     

Spontaneous regression of germinoma in the pineal region before endoscopic surgery: a pitfall of modern strategy for pineal germ cell tumors

Since its introduction in the neurosurgical field, neuroendoscopy has played an important role in the treatment of pineal germ cell tumors. The authors report a case of pineal germinoma revealing spontaneous regression before neuroendoscopic surgery. A 15-year-old boy presented with chronic headache, deterioration of his visual acuity, and diplopia. Head magnetic resonance imaging (MRI) revealed a large tumor in the pineal region and triventricular hydrocephalus due to occlusion of the aqueduct. As levels of tumor markers in serum and cerebrospinal fluid, including those of alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and the beta-subunit of hCG, were all within the normal ranges, endoscopic surgery for biopsy and third ventriculocisternostomy was performed. Under endoscopic view, the tumor was revealed to be smaller than expected from preoperative images. MRI obtained 14 days after admission disclosed marked shrinkage of the tumor. The histopathological diagnosis was pure germinoma, and the patient underwent chemotherapy combined with fractionated radiotherapy. The tumor disappeared, and the patient did not show any signs of relapse. Spontaneous regression is a very rare phenomenon in malignant brain tumors, and in the literature it has been uncommonly described in pineal germ cell tumors. Our case disclosed a pitfall of modern strategy for this pathology with neuroendoscopy. Dilated ventricles and a certain amount of lesion are factors for safe endoscopic biopsy of pineal tumors. Radiographic images shortly before surgery are warranted, especially in patients whose symptoms of intracranial hypertension have already improved before surgery.     

Glioblastoma multiforme of the pineal region

Glioblastoma multiforme (GBMs) tumors are exceedingly rare tumors in the pineal region. We present three cases in which patients presented with a pineal/posterior third ventricular region mass and review all the previously reported cases in the literature. Pineal region GBM seems to be a very aggressive tumor with a high rate of leptomeningeal and ependymal metastatic disease. Patients usually present with signs and symptoms of hydrocephalus and Parinaud’s syndrome. The clinical and radiological characteristics of pineal GBM do not differentiate it from other malignancies of this region, thus surgical biopsy is generally required for definitive diagnosis. Glioblastoma should be considered in the differential diagnosis of the pineal region tumors, especially when evidence of leptomeningeal or ependymal metastatic disease is present.     

Pineal parenchymal tumor of intermediate differentiation with papillary features: a continuum of primary pineal tumors?

Pineal parenchymal tumors comprise a rare group of primary neoplasms of the pineal gland. We describe a case involving a 29-year-old woman who presented with signs and symptoms of hydrocephalus secondary to a pineal region tumor obstructing the third ventricle. Surgical resection was performed and pathological analysis revealed a novel diagnosis consistent with a pineal parenchymal tumor of intermediate differentiation (PPTID) with transition to a papillary tumor of the pineal region (PTPR). To our knowledge, this particular pineal region tumor pathology has not yet been reported in the literature and highlights the continuum with which primary pineal tumors exist. We provide a review of the existing literature on pineal region tumors, specifically PTPR and PPTID, and offer insight into the management of these rare neoplasms.     

So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?

BackgroundThe Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed.MethodsA questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan.ResultsFifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them.ConclusionAll patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.     

Trilateral retinoblastoma: is the location of the intracranial tumor important?

BACKGROUND: Trilateral retinoblastoma refers to bilateral retinoblastoma associated with an intracranial primitive neuroectodermal tumor in the pineal or suprasellar region. The purpose of this study was to review patient and tumor characteristics and treatment outcome in patients with trilateral retinoblastoma and to determine whether there is a difference in presentation or outcome according to the location of the intracranial tumor. METHODS: A MEDLINE search of all English language articles pertaining to trilateral retinoblastoma published between 1977-1997 was performed. A total of 94 different cases were identified and analyzed. RESULTS: The gender was male in 39 patients (41.5%), female in 50 patients (53.2%), and unknown in 5 patients (5.3%). Family history for retinoblastoma was positive in 44 patients (46.8%), negative in 39 patients (41.5%), and unknown in 11 patients (11.7%). The median age at the time of diagnosis of retinoblastoma was 6 months. The median time interval to the development of an intracranial tumor from the time of diagnosis of retinoblastoma was 21 months. In 78 patients (83.0%) the intracranial tumor was in the pineal region and in 16 patients (17.0%) it was in the suprasellar region. The median time interval from the time of diagnosis of retinoblastoma to the development of a pineal region tumor was 24 months whereas the median time interval for the development of a suprasellar region tumor was 1 month. At 6 months after the diagnosis of intraocular tumors, 6 of 61 children with pineal region tumors and 10 of 14 patients with suprasellar region tumors had developed intracranial disease (P = 0.005). Unilateral intraocular retinoblastoma associated with intracranial tumor was more likely to occur in patients with suprasellar region tumors than pineal region tumors (P < 0.015). The median survival after the diagnosis of an intracranial tumor was 6 months regardless of the location of the intracranial tumor. For patients who received no treatment for the intracranial tumor the median survival was 1 month whereas it was 8 months for those who received treatment. Children who were asymptomatic at the time of diagnosis of the intracranial tumor had a better overall survival than those who were symptomatic (P = 0.002). CONCLUSIONS: The prognosis of children who develop trilateral retinoblastoma is dismal with current treatment strategies. Tumors of the suprasellar region present earlier than tumors of the pineal region after the diagnosis of intraocular tumors. Because patients who were asymptomatic at the time of diagnosis of intracranial disease had a better overall survival than those who were symptomatic, screening for intracranial tumors may be a valuable strategy in the management of patients with bilateral and/or hereditary retinoblastoma. [See editorial on pages 3-5, this issue.]