伴性早熟的儿童生殖细胞瘤临床特点及血清和脑脊液β-hcG测定对肿瘤定位诊断的价值

目的 分析伴性早熟的儿童生殖细胞瘤的临床特点,评估血清和脑脊液人绒毛膜促性腺激素β亚单位(β-hcG)检测对肿瘤定位诊断的意义.方法 2005年1月至2009年12月在中山大学附属第一医院儿科内分泌专科就诊,经病理诊断证实为分泌hcG生殖细胞瘤的男童12例,年龄(7.3±1.8)岁(4.2～10.2岁),按肿瘤部位分为颅内组和颅外组,接受治疗前同时检测血清及脑脊液β-hcG,另5位性别年龄与颅外组匹配的非生殖细胞瘤儿童作为脑脊液β-hcG枪测对照组.总结临床特点并比较颅内与颅外组血睾酮、血清和脑脊液β-hcG水平的差异.结果 12例患儿血睾酮10.43(1.70～254.00)μg/L,11例睾丸容积＞4 ml,但促性腺激素释放激素(LHRH)激发试验呈抑制状态.6例有乳房发育.颅内组与颅外组血β-hcG水平分别为63.75(8.50～309.50)IU/L、59.00(25.10～71.77)IU/L,两者差异无统计学意义(P=0.644).血β-hcG水平与年龄、肿瘤部位、病程无相关.颅内组脑脊液β-hcG水平[488.99(17.30～1048.53)IU/L]远高于颅外组[1.20(1.20～1.50)IU/L](P=0.009),后者与对照组比较差异无统计学意义.结论 男孩分泌hcG的生殖细胞瘤主要表现为外周性性早熟,或睾丸发育与LHRH激发值水平不相符合,并可伴乳房发育.联合检测血清和脑脊液β-hcG可协助肿瘤的定位诊断.     

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。     

Pathological features of intracranial germinomas with reference to fibrous tissue and granulomatous change

Intracranial germinomas are accompanied occasionally by a significant granulomatous change and abundant fibrous tissue, and this has made their pathological diagnosis difficult. However, the incidence of the granulomatous reaction and the presence of fibrous tissue together with their clinical characteristics in intracranial germinomas have not been fully investigated. Twenty-four germinomas, none of which had received preoperative treatment, were clinicopathologically examined. The location of the tumor was the pineal region (5 cases), the suprasellar region (13 cases), multiple lesions (2 cases), the basal ganglia region (1 case), and other regions (3 cases). Histologically, the germinomas could be divided into two types: (1) type A (18 cases) consisted mainly of large neoplastic cells and small lymphocytes, showing a two-cell pattern; (2) type B (6 cases) consisted predominantly of fibroinflammatory tissues containing occasional neoplastic cells (5/6 cases) and, rarely, neoplastic cells (1/6 cases). Perioperatively, two-cell-pattern germinomas (type A) were characterized as soft tumors and fibroinflammatory germinomas (type B) as hard tumors. Thus, the fibroinflammatory type B accounted for 25% of the intracranial germinomas. Although there were no topographical and clinical differences between the two types, we conclude that immunohistological studies to detect neoplastic germ cells are warranted in cases of small stereotactic biopsies of hard type B tumors.     

睾丸生殖细胞肿瘤综合治疗的长期疗效

目的 分析睾丸生殖细胞肿瘤(TGCTs)患者的临床特征、综合治疗疗效、生存率以及与预后有关的因素。方法 对107例行高位睾丸切除 精索静脉结扎术、术后均行化疗的TGCTs患者进行回顾性分析。近期疗效比较采用χ^2检验;生存率的计算采用Kaplan-Meiel生存曲线;生存率的比较采用Log rank检验。结果 107例患者中位年龄32岁。精原细胞瘤33例(30．8％),其中Ⅰ期14例,占42．4％;非精原细胞瘤74例(69．2％),其中I期21例,占28．4％。临床分期和病理类型是影响患者预后的主要因素。患者总的3,5,10年生存率分别为75．8％、73．5％和73．5％。精原细胞瘤患者3,5,10年生存率分别为100％、96．8％和96．8％;非精原细胞瘤患者3,5,10年生存率分别为63、5％、61．7％和61．7％。64例患者可评价疗效,单用化疗的患者中,17例(26,6％)达CR,另有8例(12．5％)化疗加放疗或解救手术后达CR。获CR与未获CR者5年生存率分别为91．7％和26．2％。结论 Ⅰ期TGCTs预后好。采用以化疗为主的综合治疗可明显提高转移性TGCTs患者的疗效和生存率。     

Cerebral Germinoma with Hemiatrophy of the Brain: Report of Three Cases

Summary. Summary.   Background: The authors report three cases of cerebral germinoma that occurred in young adults with unusual presentation.   Method: All three patients presented with hemiparesis and were treated at Seoul National University. A histological diagnosis of germinoma was made by a stereotactic biopsy in all three cases.   Findings: Magnetic resonance (MR) images showed that their tumors were located in the internal capsule and thalamus, and were associated with ipsilateral cerebral hemisphere and brain stem atrophy. The hemiparesis slowly progressed and this was accompanied by a haemorrhagic cyst in each patient.   Interpretation: Clinical diagnosis was not easy because of the unusual clinical presentations and atypical MR imaging findings. It is suggested that cerebral germinoma should be included in the differental diagnosis of a haemorrhagic mass which is associated with cerebral atrophy in the thalamus, basal ganglia, or internal capsule, especially in adolescents or young adults.     

Neurohypophyseal germinoma histologically misidentified as granulomatous hypophysitis

We report a case of neurohypophyseal germinoma appearing as predominantly granulomatous reaction in the first histological examination. A 12-year-old boy presented with diabetes insipidus, panhypopituitarism, and bitemporal hemianopsia. Transsphenoidal exploration for the intrasellar mass lesion extending to the suprasellar region was performed in May 1999. Histological examination revealed granulomatous hypophysitis and corticosteroid therapy was initiated. Six months later, the lesion relapsed despite corticosteroid therapy. Subtotal removal of the lesion was performed via an anterior interhemispheric approach in December 1999. Histological examination revealed typical germinoma. Subsequently, the patient underwent irradiation of 20 Gy to the tumour site and 24 Gy to the whole brain. Magnetic resonance imaging confirmed tumour remission. We must consider the possibility of neurohypophyseal germinoma in patients with granulomatous hypophysitis which does not respond to corticosteroid therapy, and perform re-exploration for more specimens to achieve the correct diagnosis.     

74例颅内生殖细胞瘤放疗疗效分析

目的 分析颅内生殖细胞瘤的放疗疗效.方法 搜集2007年11月前接近18年内收治的颅内生殖细胞瘤病例74例,其中男35例,女39例,中位年龄15(5～45)岁.放疗前病理诊断9例,余65例20 Gy放疗后MRI显示病灶均明显缩小(>50%)或消失为临床诊断.应用6 MV X线全脑全脊髓放疗加局部补量照射、全脑放疗加局部补量照射、全脑室放疗加局部补量或肿瘤区局部照射,原发病灶区38.5～50.0 Gy,全脑或全脑室18～25 Gy,全脊髓21～25 Gy,分割剂量1.6～2.0Gy/次,5次/周.结果 中位随访时间80(12～168)个月,总随访率为97%,10年随访例数和随访率分别为14例和19%.1、5、10年总生存率和无复发生存率分别为99%和97%、96%和90%、93%和83%.共9例患者治疗失败,6例为照射野内复发,3例为照射野外转移.照射野内复发者中肿瘤剂量<40 Gy者3例.38例患者放疗后有不同程度的垂体前叶功能低下,部分需强的松等激素替代治疗.结论 放疗是颅内生殖细胞瘤的主要治疗手段,其照射剂量、范围要根据病灶数目、脑脊液检查等结果 来决定.     

鞍区生殖细胞瘤的MR 影像

目的 分析鞍区生殖细胞瘤的MR影像特点。方法 经手术及病理证实的鞍区生殖细胞瘤38例,男12例,女26例,年龄3－32岁。结果 根据位置不同将其分为三类：I类,肿瘤位于第三脑室内,包括从第三脑室底向上长入第三脑室,共20例;Ⅱ类;仅位于第三脑室区,累及视交叉,漏斗、垂体柄、视神经和视束,共15例,Ⅲ类;仅位于鞍内,共3例,结论 MRI对Ⅰ和Ⅱ类生殖细胞瘤的诊断有重要价值,MRI对Ⅲ类不易作出诊断,必须结合临床。     

Germinoma with synchronous lesions in the pineal and suprasellar regions

Background Germinomas represent the most frequent tumour type in the pineal region and the synchronous involvement of the suprasellar region, frequently termed bifocal disease, is increasingly recognised. The incidence, pathogenesis, histomorphological, radiological, clinical features, and management strategies are discussed. Case report A 6-year-old girl presented with clinical features of hypothalamic–pituitary axis dysfunction. MRI showed two distinct lesions in the pineal and suprasellar regions. Tumour markers for germ cell tumours from blood and cerebrospinal fluid were within the normal range. The suprasellar lesion was biopsied and the histology revealed a germinoma. She received a radical course of radiotherapy covering the entire craniospinal axis (24 Gy/15#) followed by focal boost to the sites of primary disease (16 Gy/10#). Three months after the completion of treatment, the patient achieved a complete clinical and radiological response, which was maintained during the 13-month follow-up period. Conclusions The optimum management of primary intracranial pineal and suprasellar (bifocal) germinomas still remains controversial. The definition as either localised or disseminated disease has major implications on required treatment and its associated late morbidity. Prospective studies with large cooperative groups worldwide and consensus meetings may reduce uncertainties regarding available management options.