卵巢微乳头亚型浆液性交界性肿瘤临床病理与分子特征分析

目的 探讨卵巢微乳头亚型浆液性交界性肿瘤(micropapillary serous borderline tumor, MSBT)的临床病理学特征、免疫表型、分子改变、鉴别诊断、治疗和预后。方法 收集14例卵巢MSBT的临床资料,采用免疫组化EnVision法染色分析IMP3的表达,运用qRT-PCR法和Sanger测序法检测BRAF和KRAS的基因突变,分析其临床病理特征并复习相关文献。结果 患者年龄27～56岁,平均41.7岁;9例为双侧卵巢肿物;11例术前血清CA125值升高。肿瘤切面呈囊实性,伴囊内乳头状物。14例卵巢MSBT均呈乳头状结构,特征性的细长微乳头直接从囊壁或大的无分支乳头上发散出来,乳头长宽比>5,乳头被覆细胞呈立方至多角形,轻-中度异型性,微乳头区范围均>5 mm。5例伴微浸润;6例伴腹膜非浸润性种植;5例伴腹水均可见异型肿瘤细胞;3例伴淋巴结受累;9例伴砂粒体。免疫表型：ER、PR、CA125、CK7和WT-1均呈阳性,p53野生型,HER2、IMP3均阴性,Ki67增殖指数为5%～30%。分子病理学特征：14例中KRAS基因突变3例(3/14,...     

膀胱原发透明细胞腺癌3例临床病理特征

目的探讨膀胱原发透明细胞腺癌(clear cell adenocarcinoma, CCA)的临床病理学特征、诊断、鉴别诊断及免疫表型。方法回顾性分析3例膀胱原发CCA的临床资料,行HE和免疫组化EnVision法染色,并复习相关文献。结果 3例患者中女性2例,男性1例,平均发病年龄62岁;2例发生于膀胱颈,1例发生于膀胱后壁。镜检:肿瘤为管状、乳头状及弥漫型三种形态混合存在。小管管腔和乳头表面可见单层鞋钉样肿瘤细胞被覆。肿瘤细胞呈立方状或柱状,胞质以嗜酸性为主,局灶胞质透亮,细胞异型性明显,核分裂象多见。术后随访10～58个月,其中1例复发,余均未见复发和转移。免疫表型:Ki-67增殖指数30%～40%,CK7、PAX8、AMACR、p53、CA125均阳性。结论膀胱原发CCA临床表现及影像学检查无特异性,诊断主要依靠组织学形态及免疫表型。     

原发性腹膜透明细胞癌1例并文献复习

目的探讨原发性腹膜透明细胞癌的临床病理学特点、诊断及鉴别诊断。方法采用免疫组化法对1例原发性腹膜透明细胞癌进行检测,并复习相关文献。结果患者女性,39岁,大网膜肿物,子宫及双侧附件未见明显异常。镜下见肿瘤细胞呈实性片状、管囊状、乳头状和腺管状排列,伴出血、坏死,核分裂易见。高倍镜下见肿瘤主要由透明细胞、嗜酸性细胞和鞋钉样细胞构成。免疫表型:肿瘤细胞CK7、CEA、CA125、PAX-8、HNF1-β和Ber-EP4均阳性,CK20、CK5/6、CR、MC、CDX-2、WT-1、TTF-1、ER、PR、Villin、vimentin、CD10和CD15均阴性,Ki-67增殖指数约70%。结论原发性腹膜透明细胞癌是非常罕见的苗勒系统肿瘤,具有特征性的形态学及免疫表型,在排除转移性卵巢或子宫透明细胞癌后方可确诊。此外,还需与浆液性腺癌、子宫内膜样癌、恶性间皮瘤、卵黄囊瘤等进行鉴别。     

实性乳头状肾细胞癌1例的免疫表型和细胞遗传学特征

目的 探讨乳头状肾细胞癌(papillary renal cell carcinoma,PRCC)实性亚型的病理特点、免疫表型、细胞遗传学特征及鉴别诊断.方法 对1例实性型PRCC行HE染色观察其组织病理学特征,采用免疫组化EnVision法染色和FISH技术分别观察其免疫表型和细胞遗传学改变,并对5例经典型PRCC进行了相应的检查分析以作阳性对照.结果 组织学上,肿瘤由致密的实性片状、小管状结构伴局灶假囊状结构组成,乳头状结构不明显.肿瘤细胞中等大小,立方状或矮柱状,部分呈鞋钉样突向囊外侧,胞质少,嗜酸性,核圆形、卵圆形或略不规则形,Fuhrman核分级为2级.免疫表型和细胞遗传学特征与经典型PRCC相似,肿瘤细胞均表达Ckpan、CK7、CK19、P504S、CD10及vimentin,而WT1、RCC、S-100均不表达.FISH检测显示肿瘤细胞核3号、7号、17号染色体扩增.结论 PRCC实性亚型具有独特的组织形态、免疫表型和细胞遗传学特征与经典型PRCC相似,免疫组化和FISH检测结果有助于明确诊断.     

子宫颈HPV相关性乳头状鳞状细胞癌的临床病理分析

目的 探讨子宫颈乳头状鳞状细胞癌(papillary squamous cell carcinoma, PSCC)的临床病理学特征、诊断及鉴别诊断。方法 收集18例子宫颈PSCC临床资料,行HE和免疫组化染色,分析其临床病理特征,并复习相关文献。结果 18例患者年龄30～71岁,平均49岁,镜下活检和手术标本均可见浅表乳头状结构,伴纤维血管轴心,被覆上皮具有子宫颈高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion, HSIL)的特征。17例子宫颈活检病理学检查均为典型的PSCC,1例子宫颈虽有菜花样肿物,但活检标本未见间质浸润,行子宫颈锥切,锥切标本仍未见间质浸润。13例行根治性子宫切除,最后均诊断为子宫颈PSCC,伴间质浸润;4例活检诊断后失访。免疫表型：p16呈弥漫强阳性(块状)染色,p63、CK7阳性,CK20阴性,Ki-67增殖指数>90%,遍布上皮全层。14例行HPV DNA分型检测,其中10例HPV 16阳性(71.4%),2例分别合并HPV 53和HPV 59感染。结论 子宫颈PSCC具有典型的病理形态学表现,...     

卵巢类似性索-间质肿瘤子宫内膜样腺癌临床病理观察

目的探讨卵巢类似性索-间质肿瘤子宫内膜样腺癌(ovarian endometrial carcinoma resembling sex cord-stromal tumor,EC-SCS)的临床病理特征、免疫表型和鉴别诊断。方法对1例ECSCS进行HE和免疫组化SP染色,并复习相关文献。结果镜检:肿瘤90%以上区域由胞质透亮的梭形或短梭形细胞构成,其内混有实性条索状或中空小管样结构,类似Sertoli细胞肿瘤;仅有不到10%的区域表现为经典的子宫内膜样腺癌。免疫表型:肿瘤细胞弥漫表达CK、CK7、EMA、ER,不表达α-inhibin、PLAP以及CA125。结论 ECSCS与卵巢性索-间质肿瘤在形态上易混淆。在组织充分取材的基础上仔细寻找镜下经典的子宫内膜样腺癌的结构并结合免疫表型,有助于诊断。     

乳腺实性乳头状癌11例临床病理分析

目的探讨乳腺实性乳头状癌的临床病理学特点、免疫表型。方法对11例乳腺实性乳头状癌的临床病理学特点、免疫表型及淋巴结转移情况进行分析。结果 11例实性乳头状癌均为女性,8例为原位癌,3例伴浸润癌成分,平均年龄63.2岁。11例实性乳头状癌均表现为乳腺肿块,其中3例为乳头溢血。所有病例大体界限清楚,肿瘤细胞围绕纤细的纤维血管轴心呈实性结节状增生,肿瘤细胞形态单一,核染色质细腻,核分裂象5个/10 HPF,8例可见细胞内外黏液。免疫表型:ER、PR均弥漫强阳性,CK5/6和HER-2均阴性,5例在瘤巢周围可见稀少的p63阳性细胞,4例瘤巢周围可见CK5/6和CD10阳性细胞,3例伴浸润癌成分者,瘤巢周围无p63、CK5/6、CD10阳性细胞;5例表达神经内分泌免疫标记Syn,6例表达Cg A。9例行腋窝淋巴结清扫术,其中1例发生淋巴结转移。结论乳腺实性乳头状癌是一种少见的好发于老年女性的乳腺癌,以肿瘤细胞排列呈实性乳头状结节为特征,常有细胞内外黏液分泌,为腺腔A型乳腺癌的免疫表型,并表达神经内分泌免疫标记,预后良好,较少发生腋窝淋巴结转移。     

乳腺恶性导管内乳头状病变28例临床病理分析

目的探讨乳腺恶性导管内乳头状病变的临床病理学特征、诊断、鉴别诊断及预后。方法回顾性分析28例乳腺恶性导管内乳头状病变的临床表现,观察其组织病理学及免疫表型特征,收集随访资料并复习相关文献。结果 28例患者均为女性,平均年龄55.7岁,主要表现为乳头溢液和乳腺肿块。组织学类型:导管内乳头状癌22例、包膜内乳头状癌2例及实性乳头状癌4例。镜检:肿瘤呈乳头状或实体状,可见纤细的纤维血管轴心。肿瘤细胞形态多一致,细胞核级别低。免疫组化标记示大部分患者肿瘤细胞ER和PR均呈强阳性,HER-2、CK5/6均呈阴性;结节内CK5/6、p63、SMA均呈阴性。实性型者部分可表达CD56、Syn、CgA。Ki-67增殖指数平均为5.3%。27例获得随访资料,随访10~79个月,患者均存活。结论乳腺恶性导管内乳头状病变好发于老年女性,组织学形态多样,诊断需结合临床、组织学形态及免疫表型,应与导管内乳头状瘤鉴别。该肿瘤具有较为惰性的生物学行为,预后较好。     

乳腺恶性腺肌上皮瘤临床病理学观察

目的 探讨乳腺恶性腺肌上皮瘤(adenomyoepithelioma,AME)的临床及病理学特点、诊断及鉴别诊断.方法 运用HE染色、镜检及免疫组化染色对3例AME进行临床病理学分析,并复习相关文献.结果 肿瘤主要形态特征是由肌上皮围绕腺上皮构成的管腔所形成的双层套管结构.2种上皮有不同程度的增生,呈巢团状.肿块呈浸润性生长,细胞异型性明显,核分裂多见.免疫组化表达结果具有双相性,腺上皮表达CK8、CK18、EMA等,肌上皮表达SMA、S-100、p63等.肿瘤细胞ER、PR、Her-2阴性,CK5/6和(或)EGFR有不同程度的阳性表达,具有基底样型乳腺癌的免疫表型.结论 恶性AME十分罕见,应与乳腺肌上皮癌、化生癌、肉瘤等多种肿瘤相鉴别,其组织学特点及免疫组化表型是诊断的关键.     

胰腺实性假乳头状肿瘤3例并文献复习

目的探讨胰腺实性假乳头状肿瘤(solid pseudopapillary tumor of the pancreas,SPTP)复发和转移病例的临床病理特征、诊断、鉴别诊断、治疗及预后。方法采用HE染色和免疫组化EnV ision法分析3例SPTP的病理学及免疫表型特征,并复习相关文献。结果镜下可见肿瘤细胞围绕小血管形成特征性的假乳头状结构,可见少量出血及坏死、黏液样变性及胆固醇沉积等现象;细胞分化较好,异型性不明显,未查见细胞核分裂象。免疫表型:β-catenin、vimentin、CK、CK8、PR、CD56等均呈阳性,Syn、CEA、CgA等呈弱阳性;ER呈阴性,Ki-67增殖指数5%。结论 SPTP是胰腺外分泌肿瘤的特殊类型,临床较少见,恶性程度低,预后良好,诊断主要依赖其组织病理学特征及免疫表型。     

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.     

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.     

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.     

'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 universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.