伴有假乳头状结构的卵巢粒层细胞瘤

卵巢粒层细胞瘤常具有广泛的形态学表现。成人型粒层细胞瘤（AGCT）常见的组织学类型为弥漫型、小梁型、岛状型和微滤泡型，而幼年型粒层细胞瘤（JGCT）常为滤泡型、弥漫性或结节型混合存在。假乳头型均可存在于成人型和幼年型，容易与卵巢的其他类型的肿瘤混淆。作者报道了14例伴有假乳头状结构的粒层细胞瘤的临床病理学特征，     

小脑发育不良性节细胞瘤合并左顶叶海绵状血管瘤1例报道及文献复习

目的 探讨小脑发育不良性节细胞瘤(LDD)的临床病理特点。方法 对1例小脑发育不良性节细胞瘤合并左顶叶海绵状血管瘤进行光镜、组织化学和免疫组化观察并结合文献分析。结果 小脑叶片增厚，板层结构异常，皮质分子层增生。颗粒细胞层和蒲肯野细胞层被异常、呈平行排列的有髓纤维以及结构紊乱和异常的神经元所取代。网织染色显示瘤细胞间无网状纤维。免疫组化标记CgA、NF、Syn、vimentin和S-100蛋白均( )，Ki-67和GFAP(-)。结论 小脑发育不良性节细胞瘤为良性肿瘤，预后良好。目前对肿瘤性质是错构瘤还是真性肿瘤存有争议。诊断依赖于MRI、组织病理学和免疫组化标记。LDD是Cowden综合征的主要中枢神经系统表现，对本病患者应作全面的系统检查，以除外Cowden综合征。颅内海绵状血管瘤少见，病因不明，与Lhermitte-Duclos病或Cowden综合征之间是否相关，有待进一步研究。     

Maffucci综合征伴右腓骨内生性软骨瘤恶变1例报道并文献复习

目的 探讨Maffucci综合征伴发内生性软骨瘤恶变的临床病理学特点.方法 对1例Maffucci综合征伴发内生性软骨瘤恶变的临床资料、影像学表现和病理学形态进行回顾性分析,并复习相关文献.结果 患者为55岁女性,因右小腿疼痛、肿胀,活动受限1年半就诊.X线检查显示右侧肱骨、尺骨和桡骨,双侧股骨、胫骨和腓骨,以及双侧手足短状骨内多发性内生性软骨瘤(Ollier病),其中右腓骨中下段可见巨大块影,伴有骨皮质破坏,周界不清,内有不规则钙化.左肘关节和左跗关节畸形.另于患者的左足背和足趾,右前臂、右小腿和右臀部皮下可见7个直径为1～3 cm的暗紫色结节.临床行右小腿截肢术.镜下显示右腓骨中下段肿块为中-低分化软骨肉瘤,右小腿暗红色结节为海绵状血管瘤,伴静脉石形成.术后随访17个月,未见复发和转移.结论 Maffucci综合征是一种少见的非遗传性软骨发育异常综合征,表现为Ollier病伴发软组织血管瘤.Maffucci综合征常常在早期发生恶变,多为内生性软骨瘤恶变为软骨肉瘤,而血瘤发生恶变者极为罕见.Maffucci综合征伴有恶变的诊断需要临床、影像和病理学三者相结合.     

卵巢幼年型颗粒细胞瘤临床病理观察

目的：探讨幼年型颗粒细胞瘤的临床病理学特点及诊断要点。方法：对2例幼年型颗粒细胞瘤进行临床资料、病理形态学及免疫组织化学观察，并结合文献对其诊断及鉴别诊断进行探讨。结果：2例镜下可见肿瘤细胞卵圆形或短梭形，胞质淡染，部分空泡状，成巢分布，呈多结节样生长，与周围卵巢组织有明显分界，局部区域有黏液样变性，血管丰富，部分细胞生长活跃，核分裂易见(5~7个/HPF)，核沟不明显，未见Call-Exner小体。免疫组织化学染色结果：ER、PR、Vimentin和α-inhibit阳性，Ki-67增殖指数25%~40%不等。结论：卵巢幼年型颗粒细胞瘤是一种少见肿瘤，易与其他肿瘤混淆导致误诊，其临床病理特点应引起临床医师重视。     

肝脏原发粒层细胞瘤伴海绵状血管瘤1例报道并文献复习

目的探讨肝脏原发粒层细胞瘤(granulosa cell tumor)伴海绵状血管瘤的临床病理学特点。方法对1例肝脏原发粒层细胞瘤伴海绵状血管瘤进行组织学观察和免疫组化染色,观察其超微结构及临床影像学特点,并复习相关文献。结果患者女性,CT及MRI提示肝脏右叶可见一巨大实性肿物,低密度。肉眼见肿物突向肝脏下方,切面呈实性;另外,在肝脏膈面被膜下见一灰红色出血区,呈疏松海绵状。镜下巨大肿物中肿瘤细胞椭圆形或梭形,呈微滤泡状、小梁状排列,部分区域呈实性弥漫状分布,类似于卵巢粒层细胞;部分区域呈束状排列,间质中可见较多胶原纤维瘢痕形成,似孤立性纤维性肿瘤。肿瘤细胞核内可见小核仁,并可见纵形核沟。免疫组化结果示肿瘤细胞CD99、α-inhibin、CK8、CK18、SMA和BCL-2均(+),Ki-67增殖指数<1%。超微结构显示肿瘤细胞可见各种形式的核皱叠形成,部分细胞呈Call-Exner小体样结构排列,偶见桥粒结构,提示该肿瘤与卵巢粒层细胞瘤极其相似。结论粒层细胞瘤原发于肝脏且合并海绵状血管瘤,非常罕见,目前其临床生物学行为难以确定,需对患者进行长期随访。     

Primary granulosa cell tumor of liver associated with cavernous hemangioma: a case of report and review of literature

目的 探讨肝脏原发粒层细胞瘤(granulosa cell tumor)伴海绵状血管瘤的临床病理学特点.方法 对1例肝脏原发粒层细胞瘤伴海绵状血管瘤进行组织学观察和免疫组化染色,观察其超微结构及临床影像学特点,并复习相关文献.结果 患者女性,CT及MRI提示肝脏右叶可见一巨大实性肿物,低密度.肉眼见肿物突向肝脏下方,切面呈实性;另外,在肝脏膈面被膜下见一灰红色出血区,呈疏松海绵状.镜下巨大肿物中肿瘤细胞椭圆形或梭形,呈微滤泡状、小梁状排列,部分区域呈实性弥漫状分布,类似于卵巢粒层细胞;部分区域呈束状排列,间质中可见较多胶原纤维瘢痕形成,似孤立性纤维性肿瘤.肿瘤细胞核内可见小核仁,并可见纵形核沟.免疫组化结果示肿瘤细胞CD99、α-inhibin、CK8、CK18、SMA和BCL-2均(+),Ki-67增殖指数＜1%.超微结构显示肿瘤细胞可见各种形式的核皱叠形成,部分细胞呈Call-Exner小体样结构排列,偶见桥粒结构,提示该肿瘤与卵巢粒层细胞瘤极其相似.结论 粒层细胞瘤原发于肝脏且合并海绵状血管瘤,非常罕见,目前其临床生物学行为难以确定,需对患者进行长期随访.     

垂体柄阻断综合征72例的MRI特征及临床表现

目的分析垂体柄阻断综合征的MRI特征及临床表现,以提高对该病的认识及诊断水平。方法回顾性分析2013年至2018年间我院收治的72例经MRI诊断为垂体柄阻断综合征患者的影像及临床资料,将其按照垂体柄是否完全中断分为2组,对其影像、临床特点进行分析总结。结果 72例患者中垂体柄缺如者40例,其中2例合并全垂体功能减退,10例合并第二性征发育迟缓,4例合并第二性征缺如,1例伴智力障碍,2例伴肾上腺皮质功能减退,1例合并尿崩症;垂体柄明显变细者32例,其中1例合并全垂体功能减退,2例合并努南综合征,2例合并第二性征发育迟缓,2例合并尿崩症;72例患者均有生长发育迟缓且生长激素激发峰值5μg/L。所有患者MRI均表现为垂体后叶异位,垂体柄缺如组中37例垂体前叶发育不良,垂体柄变细组中29例垂体前叶发育不良。结论垂体柄阻断综合征所有患者均以生长发育迟缓为主要临床表现,并伴发其他发育畸形,MRI诊断的特征性标志是垂体后叶异位,临床、实验室检查提示异常时,MRI是诊断此病最有效且唯一可靠的检查方法。     

小脑发育不良性节细胞瘤/Lhermitte-Duclos病6例临床病理分析并文献复习

目的探讨小脑发育不良性节细胞瘤/Lhermitte-Duclos病(Lhermitte-Duclos disease,LDD)的临床病理学特征、诊断及鉴别诊断。方法对6例LDD进行临床病理学分析,行免疫组化SP法染色,并结合文献对该病的临床表现、组织学形态、免疫表型及预后进行分析。结果 6例患者年龄23~56岁,平均34岁,临床症状表现为颅内压增高伴或不伴小脑体征等。MRI表现为特征性"虎斑征"。光镜下表现为局部小脑结构紊乱,颗粒细胞及浦肯野细胞减少并代以多量异常神经节细胞。随访2例5~8年复发,其余4例恢复良好。结论 LDD属于小脑的罕见原发性良性病变,诊断依靠影像学和病理组织学检查,治疗方法首选完整切除。     

15例硬化性肺细胞瘤冰冻切片与临床病理特征分析

目的：回顾性分析肺硬化性肺细胞瘤组织学及临床病理特点,提高快速冰冻诊断的准确性。方法：对15例经手术切除并诊断为硬化性肺细胞瘤的病例及2例冰冻误诊为硬化性肺细胞瘤的其他病变进行回顾性分析,包括冰冻及常规切片、免疫组织化学染色,结合临床病理特征进行总结。结果：本组15例硬化性肺细胞瘤,女性13例,平均年龄46岁;临床诊断肺癌6例,余9例为其他良性病变;冰冻切片诊断6例硬化性肺细胞瘤,1例炎性假瘤,1例错构瘤,2例肺癌,3例良性病变,2例延迟诊断;肿瘤常由乳头、硬化、实性、出血4种结构中的2种或多种混合而成。冰冻切片中10例见2种组织结构,4例见3种组织结构,1例见4种组织结构;圆形细胞TTF-1、EMA(+),表面上皮细胞TTF-1、EMA和CK(+),两种细胞Ki-67指数<2%。冰冻误诊为硬化性肺细胞瘤的2例,石蜡证实1例为混合亚型腺癌,1例为肺泡性腺瘤。结论：硬化性肺细胞瘤临床和影像学易误诊为癌,冰冻切片诊断准确率低。冰冻及石蜡切片中,常可见2种或2种以上组织结构;冰冻切片中以乳头状为主时,易误诊为腺癌;以实性为主时,易误诊为类癌。借助免疫组织化学指标,常可确诊。     

具有内分泌功能的卵巢肿瘤

目的探讨具有内分泌功能的卵巢肿瘤的临床病理特征.方法对本院临床表现有内分泌功能并经手术治疗的24例卵巢肿瘤进行临床内分泌表现、组织学类型分析,并行免疫组织化学EnVision二步法染色,抗体为AE1/AE3、上皮膜抗原(EMA)、α-抑制素、Calretini、平滑肌肌动蛋白(SMA).结果 (1)临床内分泌的表现主要为性激素异常, 在幼女或绝经后妇女均有较明显的症状和体征,而在生育年龄妇女则表现的较为隐匿和复杂.(2)肿瘤的组织学类型主要为卵巢性索-间质肿瘤卵巢型13例(颗粒细胞瘤8例,泡膜纤维瘤2例,硬化性间质瘤3例),睾丸型7例(支持细胞瘤1例,支持- Leydig细胞瘤5例,Leydig细胞瘤1例),非特异性类固醇细胞瘤2例;这类肿瘤11例直径<5 cm,4例较大或巨大,最大直径达18 cm;切面多为灰粉黄色,实性或囊实性.另外2例为原发上皮性肿瘤,直径分别为12 cm和14 cm.(3)免疫组织化学染色显示卵巢性索-间质肿瘤α-抑制素全部(22/22)和Calretini绝大多数(18/22)呈阳性表达,组织形态分化好的区域表达强于分化差的区域;2例上皮性肿瘤的间质黄素化细胞也呈阳性表达.SMA在5例泡膜纤维瘤和硬化性间质瘤均呈强阳性表达,部分(3/8)颗粒细胞瘤呈弱阳性表达.部分(6/22)性索-间质肿瘤AE1/AE3阳性表达,但EMA均为阴性.结论具有内分泌功能的卵巢肿瘤多数临床表现为性激素的异常,临床表现与肿瘤的组织学类型不完全一致.其组织学类型主要为性索-间质肿瘤.非性索-间质性卵巢肿瘤也可表现为性激素异常.免疫组织化学染色可协助诊断,并用于与上皮性肿瘤鉴别.     

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.