胰腺导管内乳头状黏液性肿瘤的诊断和鉴别诊断

目的探讨胰腺导管内乳头状黏液性肿瘤的临床病理学特征及其与黏液囊性肿瘤的鉴别诊断要点。方法复习17例导管内乳头状黏液性肿瘤的临床病理学特征,与13例黏液囊性肿瘤对照;行HE染色及免疫组织化学EnVision法染色,检测肿瘤内黏液素MUC（1、2、5AC）的表达。结果17例导管内乳头状黏液性肿瘤中10例发生在男性;13例位于胰头。大体切面可观察到15例肿瘤与胰腺主导管相通。镜下可见到胰腺导管增生呈乳头状,并有上皮轻至重度不典型增生的改变。无卵巢样间质,肿瘤内交错出现萎缩或正常的胰腺腺泡和胰岛。9例主要表达MUC2,4例主要表达MUC5AC,4例伴有浸润癌者主要表达MUC1。13例黏液囊性肿瘤中11例发生于中老年女性;胰尾部10例,胰头1例,全胰腺2例;肿瘤与主导管不相通。组织学特征是含有卵巢样间质。肿瘤细胞主要表达MUC5AC,不表达MUC2,伴有浸润癌的2例,癌组织也表达MUC1。结论导管内乳头状黏液性肿瘤预后较好,患者性别、年龄、肿瘤部位、卵巢样间质、与主胰管是否相通及表达MUC2和（或）MUC1检测均可帮助诊断,并与黏液囊性肿瘤鉴别。后者主要表达MUC5AC。MUC1阳性提示侵袭性生物学行为。     

伴假腺样结构的黏液型肾上腺皮质腺瘤6例临床病理特征分析

目的探讨伴假腺样结构的黏液型肾上腺皮质腺瘤(myxoid adrenocortical adenoma,MACA)的临床病理学特征及生物学行为。方法采用免疫组化法检测6例MACA中vimentin、Syn、α-inhibin和Melan-A等的表达,回顾性分析MACA的临床病理学特征及随访,并复习相关文献。结果 6例患者年龄31~64岁,男女比为1∶2。4例既往有高血压病史。肿块重15~150 g,最大径2~11 cm。MACA肿瘤间质显著黏液变性(30%~100%),瘤细胞黏附性差,呈假腺腔样结构排列,或呈梁索状、微囊状、簇状等形态。黏液型与经典型皮质腺瘤混合。MACA不同程度表达vimentin、Syn、α-inhibin和Melan-A。间质黏液样物质阿尔辛蓝染色阳性,PAS染色阴性。术后随访11~72个月,无复发及转移。结论 MACA临床罕见,肿瘤组织结构多样,需与其他肿瘤鉴别,完整切除肿瘤后应密切随访。     

上皮样黏液纤维肉瘤1例并文献复习

目的 探讨上皮样黏液纤维肉瘤的临床病理特征.方法 对1例上皮样黏液纤维肉瘤进行光镜观察及免疫组化标记,并复习相关文献.结果 上皮样黏液纤维肉瘤好发于中老年人,多发于四肢.肿瘤呈多结节浸润性生长,疏松区和致密区交替出现,疏松区具有普通黏液纤维肉瘤的特征,致密区肿瘤细胞呈片状排列,并显示上皮样形态特点.免疫表型:肿瘤细胞vimentin阳性,Ki-67增殖指数10%～15%.结论 上皮样黏液纤维肉瘤是黏液纤维肉瘤罕见的亚型,多数为高级别肿瘤,且较普通的高级别黏液纤维肉瘤更具侵袭性.     

黏液型血管瘤样纤维组织细胞瘤的临床病理学观察北大核心CSCD

目的探讨黏液型血管瘤样纤维组织细胞瘤（AFH）的临床病理学特征、诊断及鉴别诊断。方法收集2008-2017年就诊于南京医科大学第一附属医院的3例黏液型AFH患者资料,采用EnVision法检测免疫组织化学表型,采用荧光原位杂交（FISH）法检测EWSRl基因断裂重排情况。结果3例中男性2例,女性1例,年龄分别为13、31和42岁。临床表现主要为偶然发现或缓慢生长的无痛性肿块。肿瘤位于浅表软组织（皮下、黏膜下）2例,深部软组织（腹膜后）1例。大体上肿瘤最大径分别为1、7和2cm,切面灰白质实。组织学上,肿瘤均境界清楚,有纤维性包膜及淋巴细胞鞘。肿瘤呈模糊的多结节状分布,问质广泛黏液变性（≥60％）。黏液丰富区域瘤细胞相对稀疏,呈梭形或星芒状,条索状或丝网状排列,或杂乱无章的分布于间质中;瘤细胞相对丰富区域可见经典AFH的组织／树突样细胞合体样生长,排列呈小片状、短束状、交错状或局部旋涡状。瘤细胞轻．中度异型性,核分裂象可见（≤2／10HPF）。未见肿瘤性坏死。仅1例见裂隙状出血性腔隙。另有1例部分间质出现丰富的硬化性胶原。3例均表达CD68、CDl63,2例表达结蛋白、上皮细胞膜抗原和CD99,1例表达Calponin和平滑肌肌动蛋白。S-100蛋白、CD34、CD31、CD35、CD21、广谱细胞角蛋白均阴性。FISH检测示EWSRl均阳性。2例获随访结果,分别随访6个月和89个月,未见复发或转移。结论黏液型AFH的临床表现、免疫表型、分子遗传学改变及生物学行为与经典型AFH相同．但组织形态学特殊,需要与肌上皮瘤、神经源性肿瘤等富含间质黏液的肿瘤鉴别。     

浅表肢端纤维黏液瘤1例临床病理学观察

目的 探讨浅表肢端纤维黏液瘤的临床病理学特征、诊断及鉴别诊断。方法 对1例发生于右手食指末端的浅表肢端纤维黏液瘤的临床表现、组织学形态及免疫表型进行回顾性分析,并文献复习。结果 患者男性,78岁,因右手食指末端肿块伴疼痛就诊。术中见肿块累及甲床,深至骨膜。大体可见肿块界限不清,直径约2 cm,切面灰白色,实性,质韧。镜下肿瘤位于真皮层内,无包膜。肿瘤实质由星形及梭形纤维母细胞样细胞组成,肿瘤细胞杂乱排列于间质中,部分区域呈席纹状及束状排列,间质呈黏液样及黏液胶原样。黏液样基质内见较丰富的纤细血管,并见散在的肥大细胞。肿瘤细胞温和,轻度异型。肿瘤无坏死,未见核分裂象。免疫表型:肿瘤细胞vimentin、CD34、CD99均呈弥漫阳性,EMA灶阳性,S-100、HMB-45、SMA、MSA、desmin、GFAP和CK均呈阴性。术后随访10个月,未见复发。结论 浅表肢端黏液瘤是一好发于指趾末端的软组织肿瘤,熟悉其临床病理特征,有助于与其他发生于指趾的软组织黏液性肿瘤鉴别。     

胰腺黏液性囊性肿瘤临床病理分析

目的；探讨胰腺黏液性囊性肿瘤（MCN）的临床病理学特点。方法：6例MCN均行B超或CT检查。除1例外，均作了手术切除治疗。对6例（MCN）作常规HE及免疫组织化学染色观察。结果：6例MCN中，女性4例，男性2例，平均年龄47岁，均位于胰腺体尾部。黏液性囊腺瘤（MCA）3例，囊壁内衬高柱状黏液上皮，上皮周围可见卵巢样间质组织；黏液性囊腺癌（MCC）3例，黏液上皮 有不典型增生，均有囊壁或胰腺组织的浸润，1例上皮周围可见卵巢样间质。CEA和CK 7在上皮中均阳性，c-erbB－2均阴性，间质SMA均阳性。结论：胰腺MCN是好发于中年女性的少见肿瘤，绝大多数发生于胰腺体尾部。MCA内衬高柱状上皮，上皮外来卵巢样间质包绕；MCC上皮细胞有不典型增生， 浸润性生长。MCN手术切除率高。     

乳腺黏液性病变的病理诊断与鉴别诊断

伴有黏液形成的乳腺病变包括含囊腔内黏液的乳腺纤维囊性变、黏液囊肿样病变(mucocele-like lesion ,MLL)、良性病变和(或)伴有不典型导管上皮增生(atypical ductal hyperplasia,ADH)、导管原位癌(ductal carcinoma in situ,DCIS)、黏液性乳头状病变、黏液癌和其他伴间质黏液样物质的病变.除了这些与细胞外黏液相关的病变外,小叶肿瘤、DCIS和浸润性癌,尤其是浸润性小叶癌含有胞质内黏液,还有间质的黏液样变在许多病变如纤维腺瘤和叶状肿瘤,多形性腺瘤和结节性黏蛋白沉积症均可见,恶性类似病变包括产生基质的癌和鳞癌伴黏液间质.本文重点讨论伴有细胞外黏液形成的黏液性乳腺病变的诊断与鉴别诊断,该组病变在良性病变、不典型增生、原位癌及浸润性癌的鉴别上有一定难度.     

卵巢交界性浆黏液性肿瘤临床病理分析

目的探讨卵巢交界性浆黏液性肿瘤的临床病理特征、诊断、鉴别诊断、治疗及预后。方法回顾性分析10例卵巢交界性浆黏液性肿瘤的临床病理资料,并复习相关文献。结果患者年龄27～59岁,平均45岁。5例肿瘤位于左侧卵巢,5例位于右侧卵巢。肿瘤最大直径5～13 cm,切面以囊性为主,囊壁内侧见大小不等的乳头状赘生物,囊内含黏液或黏稠胶冻样物。肿瘤组织主要由子宫颈管型黏液上皮及浆液性上皮组成,肿瘤细胞呈腺样、粗大球茎状或乳头状排列,轻～中度异型,核分裂象不易见,肿瘤间质内见特征性中性粒细胞浸润。6例肿瘤伴卵巢子宫内膜异位症,1例合并良性附壁结节,2例合并子宫内膜样癌。免疫表型:肿瘤细胞PAX-8、CK7、ER均呈阳性(10/10),PR阳性(7/10),CK20、CDX2均呈阴性(10/10),WT-1阴性(9/10),Ki-67增殖指数1%～10%。10例患者FIGO分期ⅠA期2例,ⅠB期1例,ⅠC1期4例,ⅠC2期1例,ⅠC3期2例。术后随访12～55个月,除1例在29个月盆腔包块复发以外,其余9例均未出现复发或转移。结论卵巢交界性浆黏液性肿瘤相对少见,具有独特的临床病理特征和免疫表型,手术切除治疗预后较好。     

副睾低级别子宫内膜间质肉瘤:1例报道并分子证实JAZF1/SUZ12易位

正发生在睾丸及其附件起源于苗勒管样浆液型或黏液型的肿瘤极其罕见,近年来也被逐渐认识。伴或不伴卵巢样间质的囊腺瘤、交界性肿瘤或囊腺癌是主要的类型。尽管有少数子宫内膜样腺癌的报道,但据作者所知,目前文献仍没有子宫内膜间质肿瘤的报道。作者报道1例发生在59岁男性左侧阴囊内直径2 cm的肿块,超声检测该肿块位于附睾尾,     

软组织恶性混合瘤/肌上皮癌1例并文献复习

目的探讨软组织恶性混合瘤/肌上皮癌(malignant mixed tumor/myopeithelia carcinoma, MMTMC)的临床病理特征、免疫表型、鉴别诊断及预后。方法对1例原发于大腿的软组织MMTMC进行HE和免疫组化染色,并复习相关文献。结果患者男性,75岁,3个月前发现右大腿后部占位,进行性增大。CT平扫+三维重建示:皮下不规则软组织肿瘤,大小5.4 cm×6.4 cm,边界尚清,无包膜,病灶密度不均。镜下肿瘤位于真皮深层,被纤维分隔成结节状,推挤式边界。主要呈两种组织形态:实性片状、微囊状上皮样区和结节状、岛状黏液软骨样区。瘤细胞主要呈上皮样、梭形细胞及黏液内漂浮的软骨样细胞构成。上皮样瘤细胞异型明显伴核偏位,呈浆样、横纹肌样,胞质嗜伊红或透亮,见大量病理性核分裂象。免疫表型:瘤细胞CK(AE1/AE3)和vimentin阳性,desmin、Calponin、GFAP、EMA、p63和S-100局灶阳性,INI1表达缺失。结论 MMTMC是一类罕见的软组织伴肌上皮分化恶性肿瘤,组织形态广泛,诊断主要依据临床病史、组织学形态及免疫组化标记。当发生于成人四肢时,需与黏液纤维肉瘤、黏液样脂肪肉瘤、骨外黏液样软骨肉瘤等其他形态多样的软组织肿瘤鉴别。     

先兆子痫患者HLA-DQA1、-DQB、-DPA1基因多态性

目的：探讨人类白细胞抗原HLA-DQA1、-DQB1、-DPA1基因多态性与先兆子痫发病的关系。方法：采用序列特异性引物技术（PCR-SSP） 对46例先兆子痫患者和105例正常孕妇及其新生儿进行HLA-DQ-DPA1等位基因分型。结果：所有标本共检出11种HLA-DQA1基因表型、16种HLA-DQB1基因表型、6种HLA-DPA1基因表型。先兆子痫患者HLA-DQB1＊0301基因频率高于正常孕妇，差异有显著性（Pc=0．032，RR=2．43，AR=0．30），其余各基因表型频率两组比较差异均无显著性。结论：HLA-DQB1＊0301基因可能是一种先兆子痫发病的易感基因。     

Comprehensive sequence analysis of HLA-DQA1 and -DQB1 alleles and characterization of DRB1-QAP-DQA1-DQB1 haplotypes

It is well known that both chain and β chain of HLA-DQ are highly polymorphic. However the polymorphisms outside the hypervariable region were not fully examined so far. To further clarify the polymorphisms in DQ genes, we determined the nucleotide sequences of full length cDNA, spanning from the leader sequence to the stop codon, from 15 DQA1 alleles and 15 DQB1 alleles. We identified several new DQ alleles which had identical exon 2 sequence and were different in other exons. On the basis of the sequence analyses, a comprehensive PCR-based oligotyping system for DQA1 gene was established. We then characterized DRB1-QAP(DQA1 promoter)-DQA1-DQB1 haplotypes of B-lymphoblastoid cell lines homozygous for HLA and healthy unrelated Japanese and Norwegian populations. It was revealed that DQA1 alleles, which were identical in exon 2 but different in other exons, showed close linkage disequilibrium with diferent characteristic DRB1, QAP and DQB1 alleles. These results suggest that DR-DQ haplotypes have been generated in the early stage of molecular evolution.     

HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes in Japanese multiple sclerosis patients

Japanese MS patients and controls were examined for the distribution of HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 alleles using in vitro amplification of genomic DNA and probing with sequence-specific oligonucleotides. No significant difference in frequency of the examined alleles was observed among the two groups. This is in contrast to Norwegian MS patients, where an association to a combination of certain DQA1 and DQB1 alleles has previously been demonstrated.     

HLA-DRB1, -DQA1, -DQB1 and DPB1 susceptibility alleles in Cameroonian type 1 diabetes patients and controls

It is known that certain combinations of alleles within the human leucocyte antigen (HLA) complex are associated with susceptibility or resistance to type 1 diabetes. Variable associations of DR and DQ with type 1 diabetes are documented in Caucasians but rarely in African populations; however, the role of HLA-DP genes in type 1 diabetes remains uncertain. In order to investigate the HLA class II associations with type 1 diabetes in Cameroonians, we used sequence-specific oligonucleotide probing (SSOP) to identify DRB1, DQA1, DQB1 and DPB1 alleles in 10 unrelated C-peptide negative patients with type 1 diabetes and 90 controls from a homogeneous population of rural Cameroon. We found a significantly higher frequency of the alleles DRB1*03 (χ² = 17.9; P = 0.001), DRB1*1301 (χ² = 37.4; P < 0.0001), DQA1*0301 (χ² = 18.5; P = 0.001) and DQB1*0201 (χ² = 37.4; P < 0.001) in diabetes patients compared to the control group. The most frequent alleles in the control population were DQA1*01, DQB1*0602 and DRB1*15. The DRB1*04 allele was not significantly associated with type I diabetes in our study population. We observed no significant difference between patients and controls in DPB1 allele frequency. In conclusion, the data in Cameroonian diabetes patients suggest the existence of HLA class II predisposing and specific protective markers, but do not support previous reports of a primary association between HLA-DP polymorphism and development of type I diabetes .     

The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1

DNA replication stress triggers the activation of Checkpoint Kinase 1 (Chk1) in a pathway that requires the independent chromatin loading of the ATRIP-ATR (ATR-interacting protein/ATM [ataxia-telangiectasia mutated]-Rad3-related kinase) complex and the Rad9-Hus1-Rad1 (9-1-1) clamp. We show that Rad9's role in Chk1 activation is to bind TopBP1, which stimulates ATR-mediated Chk1 phosphorylation via TopBP1's activation domain (AD), a domain that binds and activates ATR. Notably, fusion of the AD to proliferating cell nuclear antigen (PCNA) or histone H2B bypasses the requirement for the 9-1-1 clamp, indicating that the 9-1-1 clamp's primary role in activating Chk1 is to localize the AD to a stalled replication fork.