颅内转移性恶性黑色素瘤：一例报告并文献复习

目的探讨颅内转移性恶性黑色素瘤临床组织病理学及免疫组织化学特征。方法应用组织病理学及免疫组织化学检测方法对1例颅内多发转移性恶性黑色素瘤患者的两次手术标本进行观察,通过复习文献分析其组织病理学和免疫组织化学特征,提出诊断与鉴别诊断要点。结果男性患者,48岁。因颅内多发占位性病变、肿瘤卒中而行右侧额颞叶肿瘤切除术。两次手术标本组织病理学表现不一：首次右侧额叶病灶表现为异型性上皮样肿瘤细胞围绕毛细血管和纤维组织呈乳头状排列;再次手术标本为右侧颞叶,病灶表现为梭形细胞呈片巢状或束状排列,胞质丰富、淡染或透亮,胞核异型性明显、核仁呈明显嗜酸性。左侧腹股沟淋巴结活检提示肿瘤转移,且肿瘤组织局部可见大量黑色素颗粒。免疫组织化学染色肿瘤细胞弥漫表达S一100蛋白、人黑色素细胞瘤抗原45、Melan—A和波形蛋白,部分表达上皮膜抗原,而细胞角蛋白、高分子角蛋白、低分子角蛋白、胶质纤维酸性蛋白、突触素、神经微丝蛋白等表达阴性。结论颅内转移性恶性黑色素瘤的组织学表现复杂多样,临床病史和影像学资料对诊断具有重要参考价值,但明确诊断仍需依靠免疫组织化学检测结果。需注意与转移癌、脑膜肿瘤、淋巴瘤及其他含黑色素的颅内肿瘤相鉴别。     

颅内转移性恶性黑色素瘤:一例报告并文献复习

目的探讨颅内转移性恶性黑色素瘤临床组织病理学及免疫组织化学特征。方法应用组织病理学及免疫组织化学检测方法对1例颅内多发转移性恶性黑色素瘤患者的两次手术标本进行观察,通过复习文献分析其组织病理学和免疫组织化学特征,提出诊断与鉴别诊断要点。结果男性患者,48岁。因颅内多发占位性病变、肿瘤卒中而行右侧额颞叶肿瘤切除术。两次手术标本组织病理学表现不一:首次右侧额叶病灶表现为异型性上皮样肿瘤细胞围绕毛细血管和纤维组织呈乳头状排列;再次手术标本为右侧颞叶,病灶表现为梭形细胞呈片巢状或束状排列,胞质丰富、淡染或透亮,胞核异型性明显、核仁呈明显嗜酸性。左侧腹股沟淋巴结活检提示肿瘤转移,且肿瘤组织局部可见大量黑色素颗粒。免疫组织化学染色肿瘤细胞弥漫表达S-100蛋白、人黑色素细胞瘤抗原45、Melan-A和波形蛋白,部分表达上皮膜抗原,而细胞角蛋白、高分子角蛋白、低分子角蛋白、胶质纤维酸性蛋白、突触素、神经微丝蛋白等表达阴性。结论颅内转移性恶性黑色素瘤的组织学表现复杂多样,临床病史和影像学资料对诊断具有重要参考价值,但明确诊断仍需依靠免疫组织化学检测结果。需注意与转移癌、脑膜肿瘤、淋巴瘤及其他含黑色素的颅内肿瘤相鉴别。     

丛状神经鞘瘤

正丛状神经鞘瘤定义为丛状或多结节性生长的神经鞘瘤变异型,可以呈现普通型神经鞘瘤或细胞性神经鞘瘤形态。组织学形态观察,肿瘤组织由紧密、拉长的肿瘤性施万细胞组成,排列方式上致密的Antoni A型多于疏松的Antoni B型(图1),上皮样细胞形态罕见,偶见核分裂象,可见血管透明变性。免疫组织化学染色,肿瘤细胞胞质和胞核一致性表达S-100蛋白(S-100),     

脑膜瘤伴黑色素细胞移殖性增生

目的总结1例脑膜瘤伴黑色素细胞移殖性增生患者的临床特点及诊断与鉴别诊断要点。方法与结果女性患者,24岁,头部CT和MRI提示左侧枕叶占位性病变,T_1WI呈高和低混杂信号,T_2WI呈等和低混杂信号,增强扫描明显强化。临床诊断为左侧枕叶肿瘤性病变,行左侧枕后入路开颅肿瘤切除术。术中可见肿瘤表面有部分光滑包膜,色泽黑,血供极其丰富。组织学形态,肿瘤细胞呈团片状分布,部分围绕血管呈乳头状排列;肿瘤细胞中等大小,胞质丰富,可见瘤巨细胞和核内包涵体以及散在的砂粒体形成;较多色素细胞胞质内可见大量黑色素颗粒。免疫组化染色,肿瘤细胞波形蛋白、上皮型钙黏附蛋白、孕激素受体呈阳性,生长抑素受体2、胶质纤维酸性蛋白、S-100蛋白部分阳性,黑色素相关抗原45(HMB45)、黑色素-A、上皮膜抗原、细胞角蛋白、低分子细胞角蛋白和高分子细胞角蛋白、SOX10、L1细胞黏附分子、D2-40、少突胶质细胞转录因子2呈阴性,而色素细胞HMB45、SOX10呈阳性。基因检测提示NF2基因缺失。最终诊断为脑膜瘤伴黑色素细胞移殖性增生。术后未行放化疗,复查头部MRI未见肿瘤复发。结论脑膜瘤伴黑色素细胞移殖性增生临床罕见,其诊断依靠组织学形态、免疫组化染色和分子病理学检查,应注意与其他中枢神经系统含有黑色素细胞的肿瘤相鉴别。     

上皮样恶性外周神经鞘膜瘤淋巴结转移临床病理学特征:病例报告及文献复习

研究背景间叶性恶性肿瘤的转移途径以血行转移为主,而上皮性恶性肿瘤大多循淋巴管道转移,但间叶性肉瘤有时也会经淋巴管道进行转移。目的探讨上皮样恶性外周神经鞘膜瘤的临床病理学特征。方法复习1例淋巴管道转移性上皮样恶性外周神经鞘膜瘤患者临床资料,通过组织学观察、组织化学染色和免疫组织化学染色研究分析肿瘤细胞特点,并进行文献回顾。结果患者女性,42岁。临床表现为右侧腋窝4cm×4cm×3cm大小肿块伴右上臂及肩部麻木。术前影像学检查显示右侧腋窝软组织肿块影及周围多发肿大淋巴结影,考虑恶性病变。术中可见右侧腋窝多个结节状肿块,最大者约5cm×3cm×3cm大小,剖面呈灰红、灰黄色,质地坚硬,局部坏死。显微镜下观察淋巴结结构破坏,肿瘤细胞呈片状或巢状排列,可见纤细的血管纤维组织分隔,大多数肿瘤细胞呈上皮样,可见多核瘤巨细胞,核分裂象易见,部分区域间质呈黏液样变性。肿瘤细胞S-100蛋白、Sox-10蛋白、波形蛋白、Col-Ⅳ表达阳性;40%的肿瘤细胞胞核P53表达阳性;细胞角蛋白、癌胚抗原、上皮膜抗原表达阴性;Ki-67抗原标记指数>90%;网状纤维染色显示网状纤维包绕上皮细胞巢。既往曾因"右腕部肿物"行两次"肿物切除术",术后病理报告为上皮样恶性外周神经鞘膜瘤伴出血及灶性坏死,结合病史,最终诊断为右侧腋窝淋巴结转移性上皮样恶性外周神经鞘膜瘤。结论上皮样恶性外周神经鞘膜瘤主要通过血行转移,较少发生淋巴管道转移,应注意与具有相似组织学形态的肿瘤相鉴别,以免误诊或漏诊。     

(颈椎)上皮样恶性外周神经鞘瘤:一例报告并文献复习

研究背景上皮样恶性外周神经鞘瘤为临床少见的软组织恶性肿瘤,以成年男性多见。肿瘤起源于大神经,主要发生于四肢、头颈部和脊柱,为侵袭性肿瘤,局部复发率高,约有50%的患者可出现远隔部位转移。本文旨在探讨(颈椎)上皮样恶性外周神经鞘瘤的临床病理学特征。方法与结果男性患者,48岁。临床主要表现为肢体无力,以左下肢明显,并伴足踝部肿胀。MRI检查显示C3~5椎管内占位性病变,考虑椎管内肿瘤术后复发。经枕外隆突至C7水平行颈椎椎管内肿瘤切除、硬脊膜修补及椎板减压术。术中可见肿瘤大部位于C3~5水平脊神经前方、左侧椎管内和硬脊膜外,由于部分肿瘤已经固定的钛板开口向前方生长,无法全切除。术后组织形态学观察,肿瘤细胞呈片状或巢团状排列,可见神经纤维分隔,大部分肿瘤细胞呈上皮样、少部分呈梭形,核分裂象易见,部分区域可见灶性坏死。肿瘤细胞弥漫表达波形蛋白、广谱细胞角蛋白、上皮膜抗原、S 100蛋白、突触素和嗜铬素A;不表达肌动蛋白、结蛋白、黑色素瘤相关抗原HMB45、胶质纤维酸性蛋白、孕激素受体、CD34和CD31;Ki 67抗原标记指数>25%;网状纤维染色可见网状纤维包绕上皮样细胞巢;荧光原位杂交检测SS18基因易位阴性。结合病史,最终诊断为(颈椎)上皮样恶性外周神经鞘瘤。结论上皮样恶性外周神经鞘瘤组织形态学表现缺乏特征性,易与其他软组织上皮样肿瘤相混淆,须结合患者临床表现、组织形态学和临床免疫表型综合判断,以免引起误诊或漏诊。S 100蛋白检测虽缺乏特异性,但仍不失为一项诊断上皮样恶性外周神经鞘瘤有价值的指标,广谱细胞角蛋白和上皮膜抗原可呈强阳性表达。     

脑膜恶性黑色素瘤病三例临床病理及神经影像学特点

目的 探讨脑膜恶性黑色素瘤病的临床、病理及神经影像学特点.方法 对我院收治的经病理确诊的3例脑膜恶性黑色素瘤病患者进行观察,总结其临床、脑脊液细胞学、神经影像学、脑膜组织病理等方面特点.结果 3例患者均以头痛起病,随后出现脑膜刺激征.其中1例皮肤有巨大黑色素痣,1例额部黑痣破溃经久不愈,另一例无皮肤及内脏黑色素瘤,为原发性.3例患者颅脑MRI强化后显示软脑膜及蛛网膜弥漫性较均匀强化并增厚.脑脊液可见大最的异形细胞.脑膜呈黑褐色或深棕色,光镜下肿瘤细胞呈多形性,核大而圆或呈不规则形,胞质丰富,核分裂象可见,胞质内黑色素颗粒聚集,细胞排列紊乱.免疫组织化学分析S-100蛋白、波形蛋白、黑色素瘤抗体HMB-45等胞质反应阳性.结论 脑膜恶性黑色素瘤病临床主要表现为头痛及脑膜刺激征,脑脊液可见大量的异形肿瘤细胞.脑膜病理见肿瘤细胞胞质内黑色素颗粒聚集、瘤细胞排列紊乱.颅脑强化MRI对该病的诊断具有一定价值.     

鞍区和鞍上脑室外神经细胞瘤

目的探讨发生于鞍区和鞍上的脑室外神经细胞瘤的临床病理学特征。方法对1例鞍区和鞍上脑室外神经细胞瘤患者的临床表现、影像学特征、组织学形态、免疫表型和分子遗传学特征进行回顾分析并复习相关文献。结果女性患者,27岁,临床表现为反复头痛伴双眼视物模糊5个月。头部MRI显示鞍区和鞍上占位性病变,T_1WI呈等或低信号,T_2WI呈高或低混杂信号,扩散加权成像呈稍高信号,界限清晰,正常垂体结构显示不清。临床诊断为垂体腺瘤,行经鼻蝶入路垂体腺瘤切除术+脑脊液鼻漏修补术+视神经减压术,手术全切除肿瘤。组织学形态可见肿瘤细胞呈弥漫浸润性生长,部分区域可见神经毡背景;肿瘤细胞大小和形态相对一致,胞核圆形或卵圆形,染色质细腻深染,未见核分裂象。免疫组织化学染色可见肿瘤细胞胞核表达神经元核抗原和甲状腺转录因子-1,胞核和胞质表达钙视网膜蛋白,胞质表达突触素、嗜铬素A、上皮钙黏素和基质金属蛋白酶-9;胞核局灶性表达S-100蛋白,胞质局灶性表达神经微丝蛋白、细胞角蛋白8和波形蛋白;Ki-67抗原标记指数约为3%。网织纤维染色呈阴性。基因检测可见肿瘤细胞无异柠檬酸脱氢酶基因突变,无1p/19q-共缺失。最终病理诊断为脑室外神经细胞瘤(WHOⅡ级)。结论鞍区和鞍上脑室外神经细胞瘤临床极为罕见,组织学形态与发生于脑室的中枢神经细胞瘤相似,表现为肿瘤弥漫浸润性生长,肿瘤细胞形态较一致,胞核圆形,可见神经毡背景和"树枝"状薄壁毛细血管。应注意与垂体腺瘤、少突胶质细胞瘤和透明细胞型室管膜瘤等相鉴别。     

脑膜黑色素瘤

正脑膜黑色素瘤是一种源于软脑膜黑色素细胞的恶性肿瘤,呈孤立性占位效应、浸润性生长。原发性脑膜黑色素瘤组织学形态类似其他部位黑色素瘤,间变性梭形或上皮样肿瘤细胞呈疏松巢状或片状结构,胞质内富含数目不等的黑色素,部分肿瘤     

腺样型胶质母细胞瘤

目的回顾1例腺样型胶质母细胞瘤患者的诊断与治疗经过,总结此类肿瘤的组织病理学特征及诊断与鉴别诊断要点。方法与结果男性患者,63岁,临床表现为口角左偏10余天。头部MRI增强扫描提示左侧额颞叶占位性病变,考虑转移瘤可能性大。18F-脱氧葡萄糖(18F-FDG)PET显像未见恶性肿瘤征象。行神经导航联合术中超声引导下左侧额颞叶占位性病变切除术,于手术显微镜下全切除病变。组织学形态观察,肿瘤细胞呈片状或巢状多中心生长,部分肿瘤区域黏液丰富;肿瘤细胞呈条索状、筛状、腺腔样或乳头状排列;肿瘤细胞胞质较少,胞核大小较一致、呈圆形或卵圆形、核深染,偶见明显核仁;可见肾小球样血管内皮细胞增生。免疫组织化学染色,肿瘤细胞胞质弥漫性表达胶质纤维酸性蛋白、波形蛋白和同源性磷酸酶-张力蛋白,胞核表达少突胶质细胞转录因子2和P53,胞质和胞核表达S-100蛋白,胞膜表达表皮生长因子受体,不表达细胞角蛋白、上皮膜抗原、癌胚抗原、甲状腺转录因子-1、CD31、CD34、CAM5.2和异柠檬酸脱氢酶1,Ki-67抗原标记指数约为76.80%。最终病理诊断为腺样型胶质母细胞瘤。术后12 d因呼吸功能和循环功能衰竭死亡。结论腺样型胶质母细胞瘤临床极为罕见,明确诊断依靠特异性组织形态学特征和免疫组织化学染色。应注意与转移性腺癌相鉴别。     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.