儿童睾丸间质病变9例临床病理分析

目的探讨儿童睾丸间质病变的临床病理学特征。方法回顾性分析9例儿童睾丸间质病变的临床病理学及免疫表型特征,并复习相关文献。结果 9例儿童睾丸间质病变,年龄1.9～16岁,平均8.3岁。男童7例,2例社会性别为女,染色体核型均为46XY。临床表现:1例性早熟,2例性发育异常,5例主要表现为睾丸肿瘤,1例为先天性肾上腺皮质增生症并睾丸肿瘤。4例性激素水平升高。B超提示7例睾丸肿瘤,2例为双侧隐睾。病理检查:睾丸病变双侧3例,单侧6例,其中左侧4例,右侧2例;病灶直径0.1～3.0 cm。镜下观察Leydig细胞增生4例,Leydig细胞瘤4例,睾丸肾上腺残余肿瘤1例。免疫表型:Leydig细胞均表达α-inhibin、vimentin、Melan-A和Calretinin,睾丸肾上腺残余肿瘤亦可见α-inhibin、vimentin及Melan-A不同程度表达,Syn局灶表达,不表达Calretinin;8例均不表达AR。结论儿童睾丸间质病变罕见,明确不同病变的临床病理特征具有重要意义。     

肾上腺皮质癌19例临床病理特征

目的探讨肾上腺皮质癌(adrenocortical carcinoma, ACC)的临床病理学特征、免疫表型、鉴别诊断及生物学行为。方法回顾性分析19例ACC患者的临床资料,总结其临床和形态学特征、免疫表型及预后。另选60例肾上腺皮质腺瘤作为对照,采用免疫组化EnVision法和网状纤维染色比较两者的差异。结果 ACC低级别13例,高级别6例。普通型13例、嗜酸型3例、黏液型1例、肉瘤样型2例。免疫表型:SF-1(100%,19/19)均阳性,α-inhibin(52.9%,9/17)强阳性,Melan-A(73.7%,14/19)局灶或部分阳性,α-inhibin和Melan-A共阳性(47.1%,8/17);Ki-67增殖指数5%～50%,60例皮质腺瘤Ki-67增殖指数均3%。ACC网状结构评分2分者2例,3分者11例,4分者6例;皮质腺瘤评分均为1分。结论 ACC中Ki-67增殖指数明显高于皮质腺瘤,网状结构评分明显高于皮质腺瘤,联合Ki-67增殖指数与网状纤维染色可与皮质腺瘤进行鉴别。     

伴有特殊形态子宫内膜间质肉瘤10例临床病理特征分析

目的探讨低级别子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS)变异形态的临床病理特点。方法回顾性分析10例LGESS的临床病理特征、免疫表型特征并对患者进行随访。采用免疫组化En Vision两步法检测CD10、vimentin、ER、PR、SMA、desmin、H-caldesmon、α-inhibin和Ki-67的表达,并复习相关文献。结果10例LGESS平均发病年龄47. 5岁,肿块最大径4. 1～12. 2 cm;镜下除经典形态外,8例见黏液变,4例伴平滑肌分化,3例呈印戒细胞样形态,2例伴纤维化,2例间质出现石棉样纤维,2例微囊性变,1例伴广泛玻璃样变性,1例同时出现性索样、腺管样、腺瘤样瘤样、梁状、囊性变、伴横纹肌分化等形态,1例子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)卵巢转移灶见蜕膜样形态。10例LGESS均表达CD10、vimentin,1例ER、PR阴性,ESS瘤细胞中Ki-67增殖指数均10%,1例伴性索样分化ESS局部α-inhibin阳性,在伴有平滑肌分化的区域H-caldesmon阳性(4/10)、desmin(4/10)阳性、SMA(6/10)阳性。结论 LGESS特殊变异形态给病理医师带来病理诊断上的挑战,联合应用免疫组化及基因检测可为临床提供更精准的病理诊断。     

鼻腔小细胞恶性肿瘤26例临床病理分析

目的 探讨鼻腔小细胞恶性肿瘤的病理形态学和免疫组化染色的特点.方法收集26例鼻腔小细胞恶性肿瘤,通过常规HE及免疫组化染色进行观察.结果 恶性黑色素瘤11例,可见突出的嗜酸性核仁、核沟、核内假包涵体,表达S-100蛋白、HMB-45、Melan-A.嗅神经母细胞瘤7例,可见神经原纤维、菊形团结构,NSE、Syn阳性,S-100蛋白在肿瘤周边的支持细胞中表达.横纹肌肉瘤4例,瘤细胞多嗜酸性,desmin、vimentin、MyoDl、Myogenin阳性.小细胞神经内分泌癌2例,可见较多的凋亡、坏死和出血,NSE、Syn、CgA均阳性.骨外Ewing肉瘤/原始神经外胚层肿瘤2例,可见Homer-Wright假菊形团及乳头状结构,CD99、vimentin、Syn、NSE均阳性.结论 鼻腔小细胞恶性肿瘤具有相似的临床和形态学表现,因此,只有根据其各自的形态学和免疫组化染色特点,才可做出正确的诊断及鉴别诊断.     

混合性嗜铬细胞瘤-节细胞神经瘤临床病理特征并文献复习

目的探讨混合性嗜铬细胞瘤(composite pheochromocytoma,CP)-节细胞神经瘤的临床病理学特征、免疫表型、鉴别诊断及预后。方法对3例CP-节细胞神经瘤行免疫组化SP法染色,并复习相关文献。结果男性1例,女性2例,年龄37~64岁;其中例3为纵隔原发。镜下见瘤组织均由两种成分构成:一种为瘤细胞,核圆形或卵圆形,胞质细颗粒状,排列成器官样,核分裂象罕见;一种为束状排列的神经纤维瘤样背景下,散在及聚集分布的神经节细胞;结节边缘尚可见残留的肾上腺组织。免疫表型:嗜铬细胞瘤成分中CD56、CgA、Syn、vimentin均阳性,SMA、Melan-A、α-inhibin、NF均阴性,S-100支持细胞阳性,Ki-67增殖指数低;节细胞神经瘤成分中NF、S-100均阳性,Ki-67增殖指数低,其内神经节细胞中CgA、Syn弱阳性或阴性。结论CP是相对较罕见的肿瘤,而节细胞神经瘤为相对常见的一种混合成分,其在临床及放射学上无法与嗜铬细胞瘤区分,目前仅基于肿瘤的组织病理学特征进行诊断,需根据其内混合的不同成分(良性或恶性)来采取相应的临床治疗与随访。     

胰腺囊性肿瘤53例临床病理特征

目的 探讨胰腺囊性肿瘤(pancreatic cystic neoplasm, PCN)的临床病理学特征。方法 收集53例PCN的临床病理资料，行HE及免疫组化EnVision法检测，并复习相关文献。结果 53例PCN中浆液性囊性肿瘤(serous cystic neoplasm, SCN)22例，实性假乳头状肿瘤(solid pseudopapillary neoplasm, SPN)13例(伴高级别转化1例),黏液性囊性肿瘤(mucinous cystic neoplasm, MCN)12例(伴相关浸润性癌2例，伴高级别异型增生1例),导管乳头状黏液性肿瘤(intraductal papillary mucinous neoplasm, IPMN)6例(伴相关浸润性癌1例，伴原位癌2例)。免疫表型：(1)22例SCN:22例均表达上皮标志物CK、CK7、CK19,10例表达α-inhibin, 22例均不表达CgA、Syn、CD56、vimentin, Ki-67增殖指数均约1%;(2)13例SPN:13例均表达PR、CD10及β-catenin, 6例表达vimentin, 5例...     

子宫腺瘤样瘤49例临床病理分析

目的探讨子宫腺瘤样瘤的组织发生、临床病理特点及鉴别诊断。方法分析49例子宫腺瘤样瘤临床病理学资料，其中14例行特殊染色和免疫组化染色。结果49例子宫腺瘤样瘤占同期子宫标本的1．3％，肿瘤多位于子宫肌壁间，其次为近子宫角和宫体或宫底浆膜下，内膜下少见。肿瘤直径0．5～5cm，临床表现无特征性。瘤细胞组成形态不一的腺样及腔隙样结构，腔隙内衬以扁平或立方上皮细胞，大多数表现为脉管样形态。全部病例均伴平滑肌增生。14例腔隙内黏液物Alician B1ue染色阳性，PAS染色阴性。免疫表型：不同类型CK、vimentin、SMA及calretinin阳性，FⅧRAg、CEA、EMA、ER及PR阴性。结论子宫腺瘤样瘤并非罕见，临床和病理上均易误诊和漏诊。瘤细胞表达CK和calretinin，不表达FⅧRAg、CEA和EMA，上述指标对子宫腺瘤样瘤的诊断和鉴别诊断均具有重要意义。本组研究结果也支持子宫腺瘤样瘤为间皮来源。     

胰腺透明细胞变异型实性-假乳头状肿瘤1例并文献复习

目的 探讨胰腺透明细胞变异型实性-假乳头状肿瘤(clear cell variant of solid pseudopapillary neoplasm, ccSPN)的临床病理学特征。方法 回顾性分析1例ccSPN的临床资料，采用免疫组化EnVision两步法检测CK、vimentin、CD10、β-catenin、CD56、Syn、CgA、E-cadherin、Ki-67的表达，分析蛋白表达与临床病理特征的关系，并复习相关文献。结果 患者女性，54岁，以腹部疼痛为首发症状，MRI示胰体尾部占位伴钙化。镜下见肿瘤界尚清，瘤细胞体积小，形态温和，呈巢状或小梁状排列，大部分胞质内含大小不等的空泡或胞质完全空泡化，细胞核圆形或卵圆形，核仁不明显，未见明确核分裂象。瘤组织被透明变的间质分隔，局部黏液样变。免疫表型：vimentin、CD10、β-catenin、CD56、Syn均阳性，CK、E-cadherin、CgA均阴性，Ki-67增殖指数约2%。结论 ccSPN是实性-假乳头状肿瘤的一种罕见变异型，行影像学检查，并尽早手术切除及长期随访是疾病诊治的关键。     

骨外黏液样软骨肉瘤2例报道及文献复习

目的探讨骨外黏液样软骨肉瘤的临床病理学特征。方法对2例骨外黏液样软骨肉瘤进行光镜观察及免疫组化染色标记,并通过相关文献复习,对病理诊断及鉴别诊断等指标进行分析。结果1例发生于足底,1例发生于乳腺。光镜下肿瘤呈分叶状,边界清。细胞为圆形及短梭形,成束状排列于黏液样基质中,局部可见围血管形成玫瑰花结样结构。部分肿瘤细胞异型性明显。免疫表型:vimentin、NSE、Syn均呈阳性;例1EMA灶性阳性,例2阴性;S-100蛋白、CgA及CK均阴性。结论骨外黏液样软骨肉瘤为罕见的软组织恶性肿瘤,具特异性的组织病理学特点。主要发生于四肢,少数可发生于实质器官,至今未有乳腺原发病例报道。部分肿瘤细胞可发生间变导致诊断困难,须与脊索瘤、骨内软骨肉瘤、化生性癌及黏液性肿瘤等鉴别。     

黏液型滑膜肉瘤2例并文献复习

目的探讨黏液型滑膜肉瘤(myxoid synovial sarcoma,MSS)的临床病理学特征、诊断及鉴别诊断。方法对2例MSS进行组织形态学观察、免疫组化染色、分子病理学检测并复习相关文献。结果例1男性,例2女性。年龄分别为71岁及15岁。例1肿物位于左下腹,例2肿物位于左侧额颞叶。镜检:例1低倍镜下肿瘤呈结节样,结节内肿瘤由细胞疏松区与致密区组成。疏松区细胞呈漩涡状、束状、片状排列,间质见大量黏液样基质,细胞异型性明显。致密区细胞丰富,瘤细胞呈束状、鱼骨样排列。例2肿瘤由细胞疏松区及致密区组成,两者间相互移行。疏松区细胞呈疏松网状、片状排列,间质见大量黏液样基质。部分区域见少量上皮样细胞,呈小簇状分布。致密区细胞丰富,呈束状、片状排列。未侵犯脑组织。免疫表型:例1,BCL-2、vimentin阳性,α-SMA和EMA部分细胞阳性,CD34、CD57、S-100、CD117、PLAP均阴性。例2,BCL-2阳性,Myo D1胞质阳性,GFAP、Olig-2、EMA、Syn、CD99、Cg A、S-100、Myogenin、STAT6、CD34、desmin、α-SMA均阴性。分子病理学检测:2例均检测到SYT-SSX融合基因。结论 MSS是一种罕见的软组织恶性肿瘤,确诊主要依靠分子病理学检测,临床与病理均需与黏液型纤维肉瘤、孤立性纤维性肿瘤等鉴别。治疗以手术切除联合放疗为主,预后不良。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.