胰腺囊性-实性肿瘤的临床病理诊断

目的：探讨胰腺囊性－ 实性肿瘤临床病理、免疫组化特点、组织发生及生物学行为。方法：对２ 例胰腺囊性－ 实性肿瘤进行光镜观察及免疫组化染色。结果：２ 例均为年轻女性（２１ 岁和３５ 岁）。肿物为半囊半实性。ＨＥ染色片中瘤细胞大小形态较一致,核圆形或卵圆形,核异型性不明显,核分裂象罕见。肿瘤细胞围绕纤维血管复层排列形成假乳头突起为其特征。免疫组化染色显示α１ＡＴ、ＥＲ和ＰＲ均阳性,ＣＥＡ、Ｓ１００ 、ＮＳＥ均阴性。随访：１ 例带瘤生存２ 年后死亡,１ 例术后９ 个月健在。结论：胰腺囊性实性肿瘤可能来源于腺泡细胞,为性激素依赖性肿瘤,具有侵袭性行为,是一种低度恶性肿瘤。     

胰腺低分化神经内分泌癌44例临床病理分析

胰腺低分化神经内分泌癌( NEC)非常罕见,包括小细胞癌及大细胞神经内分泌癌,其相关临床病理特征方面的资料非常有限。根据WHO(2010)胃肠胰神经内分泌肿瘤分类及分级标准(核分裂象/Ki-67增殖指数),对107例最初诊断为低分化NEC的胰腺切除病例进行重新评估。采用免疫组化法检测神经内分泌及腺泡标志物。63例被重新分类为高分化神经内分泌肿瘤( NET)或腺泡细胞癌。对其余44例低分化NEC的临床病理特征及生存预后情况进行进一步评估。患者平均年龄59岁(范围21~82岁),男女比例为1：4。27例肿瘤位于胰头部,3例位于胰体,11例位于胰尾。肿瘤中位直径4 cm(范围2~18 cm)。27例为大细胞NEC,17例为小细胞癌(平均核分裂象分别为37个/10 HPF、51个/10 HPF;Ki-67增殖指数分别为66%及75%)。8例肿瘤含有混合性成分,大多数为腺癌。此外,2例肿瘤具有高分化NET成分。88%的病例在诊断时即伴有淋巴结或远处转移,另有7%的病例在诊断后出现远处转移。43例具随访信息,33例死于疾病,中位生存期11个月(范围0~104个月);8例带瘤存活,中位随访期19.5个月(范围0~71个月)。2年及5年生存率分别为22.5%和16.1%。胰腺低分化NEC为高侵袭性肿瘤,易发生转移,生存率低下。大多数患者在1年内死亡。61%病例是大细胞NEC。高分化NET及腺泡细胞癌常被误诊为低分化NEC,因此诊断时必须严格遵循诊断标准。     

小肠肉瘤样癌临床病理分析

目的探讨小肠肉瘤样癌的临床病理学特点及免疫组织化学表型。方法采用光镜结合免疫组化SP法对6例小肠肉瘤样癌标本进行观察分析。结果6例小肠肉瘤样癌患者中男性5例,女性1例;年龄43～72岁,平均61．3岁。肿瘤平均直径为5．5cm。呈菜花状或息肉状。光镜下可见3种肿瘤细胞：上皮样细胞、梭形细胞及间变性细胞,多呈片状或束状排列,偶呈巢状排列。免疫组化显示：6例vimentin、CKpan、EMA及CK7均为强阳性;CK20有两例弱阳性;CEA有1例弱阳性;NSE及Syn在6例均为阳性表达,CgA3例阳性,阳性强度为弱阳性～中等阳性;Ki-67阳性指数为37％～73％,平均值为51．6％。随访4例患者在术后2～7个月内死亡。结论小肠肉瘤样癌罕见,多发于老年男性,免疫组化证实有上皮及神经内分泌分化,预后很差,免疫组化在鉴别诊断中很重要。     

直肠神经内分泌肿瘤临床病理特点及分级

目的探讨直肠神经内分泌肿瘤的病理特征及分级。方法对49例直肠神经内分泌肿瘤进行临床及病理资料整理,应用SP法免疫组化染色。结果神经内分泌肿瘤Ⅰ级42例,神经内分泌肿瘤Ⅱ级4例,其中3例伴肠系膜淋巴结转移。组织构型上可分为实性小巢状或岛状、梁状、腺管状、混合性4种。神经内分泌肿瘤Ⅲ级3例,2例为大细胞神经内分泌癌,其中1例伴腹股沟淋巴结转移,1例为小细胞癌,伴肝脏转移。免疫表型除外会诊5例未做免疫组化,其余均做免疫组化SYN、Cg A及Ki-67,其中SYN所有病例均阳性,Cg A阳性8例,Ki-67因级别不同,增殖指数相差较大。结论直肠神经内分泌肿瘤Ⅰ级最多见,生物学行为低度恶性,一般不侵犯肌层,也很少转移,大多数病例可以在内镜下行黏膜切除术获得治愈。Ⅱ级和Ⅲ级生物学行为侵袭性,伴淋巴结转移及肝转移。免疫组化SYN、Cg A及Ki-67染色可作为神经内分泌肿瘤的常规免疫标记物。     

胰腺囊实性肿瘤的免疫组化及超微结构观察

目的：了解胰腺囊实性肿瘤的免疫组化及超微结构特点。分析其临床病理特点与预后的关系。方法：用HE、过碘酸雪夫（PAS）和免疫组化（S-P法）及电镜观察7例胰腺囊实性肿瘤。结果：肿瘤较大，包膜较完整，囊实相同，显微镜观察HE染色片中瘤细胞大小形态较一致。核圆形或卵圆形，核异型不明显，核分裂象罕见，肿瘤细胞围绕纤维血管复层排列形成假乳头片中瘤细胞大小形态较一致。核圆形或卵圆形，核异型不明显，核分裂象罕见，肿瘤细胞围绕纤维血管复层排列形成假乳头突起为其特征。免疫表型，波形蛋白2例表达阳性，低分子量角蛋白6例为阳性，突触素4例为阳性，α1-AT6例阳性，胰岛素2例阳性，高分子量角蛋白，上皮膜抗原，生长抑素均为阴性，超微结构观察，4例瘤细胞分化良好，有数个细胞内含有类似酶原颗粒小体，直径0.8-1.2μm，有界膜，电子密度不均。结论：胰腺囊实性肿瘤可能起源于胰腺腺泡又具有内分泌特征，临床经过表现为良性，预后良好。     

子宫颈腺样基底细胞癌4例临床病理观察

目的探讨子宫颈腺样基底细胞癌的临床病理特征、诊断、鉴别诊断及预后特点,以提高对该病的认识及避免过度治疗。方法对4例子宫颈腺样基底细胞癌的临床及病理资料进行回顾性分析,运用常规HE、免疫组化EnVision法染色及原位杂交技术进行检测,并复习相关文献。结果 4例子宫颈腺样基底细胞癌患者年龄53~67岁,平均61.5岁,4例患者均行全子宫+双侧附件切除术。镜下见癌组织由形态单一、分化良好的基底样小细胞组成,排列成小巢状或条索状。癌巢周边见栅栏状排列的细胞核,部分癌巢中央形成囊性腔隙,也可见腺样或鳞状分化。4例患者均伴子宫颈上皮内病变(cervical intraepithelial neoplasia,CIN)。免疫表型:肿瘤细胞CK5/6、CK8/18、CK19、p16、p40、p53、BCL-2和p63均阳性,ER、CK7、CEA、CD117和S-100均阴性。原位杂交检测:HPV16/18阳性。4例患者随访19~62个月,均未见复发及转移。结论子宫颈腺样基底细胞癌属于罕见但预后较好的肿瘤,因预后不同,需与腺样囊性癌、基底样鳞状细胞癌、神经内分泌癌及腺鳞癌鉴别。治疗可选择全子宫切除术或宫颈锥切术,不推荐放、化疗。     

双相性鳞片状腺泡状肾细胞癌:乳头状肾细胞癌的一种特殊亚型?

正双相性鳞片状腺泡状肾细胞癌(BSARCC)是最近阐述的一种具有特殊形态学特征的肿瘤。本文使用常规组织学、免疫组化、阵列比较基因组杂交技术(aC GH)及荧光原位杂交技术分析来自12家医院的21例BSARCC。男性11例,女性10例,年龄范围53~79岁;肿瘤直径1.5~16 cm;14例患者获得随访信息(随访1~96个月),5例发现转移性播散。所有肿瘤均由两种细胞群构成,呈器官样结构排列:缺乏胞质的、小的低级别瘤细胞通常衬覆在腺泡状结构的里面,而     

Pan-TRK免疫组化在涎腺分泌性癌中敏感性与特异性的临床病理分析

目的 探讨Pan-TRK免疫组化在涎腺分泌性癌(secretory carcinoma of salivary glands, SCSG)诊断及鉴别诊断中的价值。方法 收集14例SCSG临床资料，采用免疫组化、FISH对SCSG进行检测。另选取经典的腺泡细胞癌、黏液表皮样癌、腺样囊性癌各10例作为对照。结果 14例SCSG患者男女比为4∶3,年龄15～79岁，10例发生于腮腺，2例发生于颊部，1例发生于腭部，1例发生于颈部；11例生存状态良好，1例复发生存，2例失访。14例SCSG,多呈浸润性生长，呈微囊状、乳头-囊状、管状、实性排列或几者混合，腔内伴丰富分泌物，1例见神经侵犯，1例伴淋巴结转移。免疫表型：14例SCSG中CK7、S-100、Mammaglobin均阳性，11例SOX-10阳性，10例GATA-3阳性，14例DOG1均阴性，Ki-67增殖指数为1%～15%。FISH检测：12例SCSG成功检测到FISH信号，10例发现ETV6-NTRK3基因融合阳性。14例SCSG均行Pan-TRK免疫组化检测，10例细胞核阳性，1例细胞质阳性。10例腺泡细胞癌、10例黏液表皮样癌、1...     

胰腺实性型浆液性囊腺瘤1例临床病理观察

目的探讨胰腺实性型浆液性囊腺瘤(solid-type serous cystadenoma,SSCA)的临床病理学特征。方法观察1例罕见的胰腺SSCA,结合文献分析其病理特征及鉴别诊断。结果患者为67岁男性,体检发现胰头占位。肿瘤肉眼实性、质韧,镜下境界清楚,呈结节状或分叶状,间质富含血管;肿瘤细胞呈紧密排列的实性巢、小腺泡、小腺管,局灶或散在可见小囊腔形成;肿瘤细胞呈立方或多边形,胞质丰富透明或淡嗜酸颗粒状,核小而圆,未见明显异型性及核分裂象。免疫表型:肿瘤细胞CK7、CK19、AAT、Inhibin-α、Calponin、MUC1、NSE均阳性,Ki-67增殖指数低,神经内分泌标记CgA、Syn、CD56及其他鉴别标记均阴性。术后随访22个月,未见复发或转移。结论 SSCA是胰腺浆液性囊性肿瘤的罕见亚型,患者手术切除预后良好,最终确诊依赖于病理检查。     

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 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.     

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.