化生性胸腺瘤2例临床病理分析

目的：探讨化生性胸腺瘤的临床及病理学特征。方法：应用光镜及免疫组织化学方法观察2例化生性胸腺瘤的组织学特点及免疫学表型,并复习相关文献。结果：2例均为男性,年龄55岁及56岁。组织学肿瘤显示双相分化特点,上皮细胞区域与梭形细胞区域交错分布并相互移行。上皮细胞呈相互吻合的束状、岛状及宽大的梁状排列,细胞轻度异型,可见核沟及核内假包涵体,偶见核分裂像;梭形细胞呈短束状或席纹状排列,细胞温和,未见核分裂像。免疫表型：上皮细胞区域CK19和AE1/AE3呈强阳性表达,上皮膜抗原（epithelial membrane antigen,EMA）弱阳性;梭形细胞区域表达Vimentin、Bcl-2及CD99,AE1/AE3局灶阳性,EMA弱阳性。两种区域中Ki67指数均〈5%。间质淋巴细胞CD3、CD5、CD20阳性,不表达Td T和CD99。结论：化生性胸腺瘤是一种罕见的良性或低度恶性胸腺肿瘤,诊断依靠病理组织学和免疫组织化学标记,完整切除预后良好。     

胸腺神经内分泌癌7例临床病理分析

胸腺神经内分泌癌罕见，是一种特殊型胸腺肿瘤。我们报道7例，并结合文献对其临床病理特征及鉴别诊断进行探讨。     

化生性胸腺瘤临床病理分析

目的探讨化生性胸腺瘤的临床病理特点。方法应用光镜、免疫组织化学(EnVision法)染色[单克隆抗体选用AE1/AE3、波形蛋白、上皮膜抗原(EMA)、CD3、CD5、CD20、CD34、CD57、CD99、末端脱氧核苷酸转移酶(TdT)、HMBE-1、calretinin、p53和Ki-67]和透射电镜观察3例化生性胸腺瘤的组织学特点、免疫学表型和超微结构。结果3例化生性胸腺瘤均为女性,年龄为33、58和45岁。组织学表现为双相分化特征,上皮细胞区域与梭形细胞区域交错分布并相互移行。上皮细胞区域的细胞轻度异型,有核沟和核内假包涵体,核分裂象罕见,呈岛状和条索状排列并相互吻合;梭形区域细胞形态温和,未见核分裂象,排列成束状或席纹状结构。免疫组织化学染色:上皮细胞区域AE1/AE3强阳性表达,不表达波形蛋白和CD5,Ki-67指数3%~5%;梭形细胞区域波形蛋白弥漫表达,EMA阳性,不表达CD5和CD20;间质淋巴细胞CD3阳性,不表达TdT和CD99。超微结构示上皮细胞区域细胞间有桥粒和半桥粒结构,而梭形细胞区域缺乏。结论化生性胸腺瘤是一类罕见的具有独特临床病理特征的良性或低度恶性胸腺上皮来源肿瘤。     

胸腺上皮肿瘤分级的临床病理意义

目的提出胸腺上皮肿瘤（TET）分级标准,并探讨该分级与WHO组织学分型、临床分期的相关性及其临床病理学意义。方法对200例TET采用WHO病理分型和Masaoka临床分期,结合临床治疗和随访资料进行了系统的相关性研究并进行了TET分级。结果胸腺瘤A型8例（4.0%）,AB型68例（34.0%）,B1型17例（8.5%）,B2型39例（19.5%）,B3型27例（13.5%）,C型36例（18.0%）,其他5例（2.5%）。组织学分型与预后的相关性有非常显著性意义（P＜0.001),A和AB型预后好,无一例患者死于肿瘤,B2、B3和C型较差。临床Ⅰ期96例（48.0%）,Ⅱ期26例（13.0%）,Ⅲ期65例（32.5%）,Ⅳ期13例（6.5%）。临床分期与预后的相关性亦有非常显著性意义(P＜0.001）,Ⅲ期和Ⅳ期预后较差。组织学分型与临床分期的相关性同样有非常显著性意义（P＜0.001）,组织学分型提示在Ⅰ期、Ⅱ期TET中,B2、B3和C型的预后明显较其他类型差（P＜0.001）。根据TET的组织学、临床资料、生物学行为和预后情况提出了TET分级的建议胸腺瘤Ⅰ级、Ⅱ级、Ⅲ级和Ⅳ级,统计学分析表明TET分级与患者的治疗和预后的相关性有非常显著性意义（P＜0.001）,Ⅰ级和Ⅱ级TET在根治术后仅需密切随访,一般不需过度治疗。本组病例中伴重症肌无力30例（15.0%）,最多见于B2和B3型胸腺瘤。结论TET的WHO组织学分型可以作为独立的预后指标;TET的分级有助于病理和临床的统一,可提示临床医师采取合适的治疗策略和正确判断预后。     

微结节性胸腺瘤伴淋巴样间质3例临床病理观察

目的:探讨微结节性胸腺瘤伴淋巴样间质(micronodular thymoma with lymphoid stroma,MNT)的临床病理特征.方法:通过组织学和免疫组织化学方法观察3例MNT,研究其临床病理特征,并复习文献.结果:肿瘤有纤维性假包膜,肿块内见多发性散在或局部融合的上皮性结节,由丰富淋巴细胞间质分隔,其中可见淋巴滤泡形成.上皮性结节由温和的细长形或卵圆形细胞组成,核仁不明显,结节内淋巴细胞稀少.免疫组织化学:上皮性结节内上皮细胞CKpan,CK5/6,CK19,CK8/18均阳性,Ki67约2%阳性,CD20,EMA阴性;间隔内淋巴细胞CD20,CD3,CD5,CD99,TdT均灶区阳性,p53,CD1α均散在阳性;淋巴细胞背景内CK5/6,C8/18,EMA均阴性.结论:MNT是一种罕见的胸腺肿瘤,目前WHO归于交界性,有特殊的发病部位和形态学表现,组织学及免疫组织化学有助于该肿瘤的诊断和鉴别诊断.     

伴淋巴间质的微结节型胸腺肿瘤5例临床病理特征

目的 探讨伴淋巴间质的微结节型胸腺肿瘤(mi-cronodular thymic neoplasm with lymphoid stroma,MTN)的临床病理特征、诊断及鉴别诊断.方法 回顾性分析5例MTN的临床特点、组织学形态及免疫表型,并复习相关文献.结果 5例患者中2例为伴淋巴间质的微结节型胸腺癌(micron...     

胸腺上皮性肿瘤中PD-L1与MMR的表达及临床意义

目的探讨PD-L1、错配修复(mismatch repair, MMR)蛋白在胸腺上皮性肿瘤(thymic epithelial tumors, TET)中表达及与临床病理特征的关系。方法收集TET标本60例,其中胸腺瘤46例,胸腺癌14例。采用免疫组化法检测PD-L1和MMR蛋白的表达。结果 60例TET中PD-L1阳性率为58.33%,PD-L1在B3型胸腺瘤和胸腺癌中的表达高于其他类型胸腺瘤(P0.05),与患者性别、年龄、肿瘤大小等临床特征之间均无统计学意义(P0.05)。60例TET中11例MMR蛋白缺失,以MLH1和PMS2联合缺失为主。MMR蛋白缺失在A型胸腺瘤中高于其他类型胸腺瘤和胸腺癌(P0.05),与患者性别、年龄、肿瘤大小等临床特征之间均无统计学意义(P0.05)。PD-L1表达与MMR蛋白缺失之间无相关性(P0.05)。结论 PD-L1表达与TET组织恶性程度高相关,MMR蛋白缺失主要为A型胸腺瘤;PD-L1表达与MMR蛋白缺失之间无相关性。     

胸腺上皮性肿瘤中不同克隆号PAX8抗体的表达及临床意义

目的 探讨不同克隆号PAX8抗体在胸腺上皮性肿瘤中的表达及临床意义.方法 采用免疫组化EnVision两步法检测鼠单克隆抗体PAX8(克隆号MRQ-50)及兔单克隆抗体PAX8(克隆号EP298)在142例胸腺上皮性肿瘤、40例甲状腺具有胸腺样分化的癌、3例胸腺鳞状细胞癌肺转移和29例肺原发鳞状细胞癌中的表达;同时亦检...     

上皮样血管内皮瘤的临床病理分析

目的：探讨上皮样（组织细胞样）血管内皮瘤的临床病理学特点及其意义。方法：对9例上皮样血管内皮瘤进行光镜和免疫组织化学SP法检测,1例作电镜观察,结果：年龄16－47岁,平均32岁,男女性别差异无显著性意义。部位：头面部4例,上肢3例,下肢2例,形态特征：瘤细胞具有上皮样或组织细胞样的形态;瘤细胞圆形或多角开,三五成群呈小巢状,索状,不规则状排列,分布于粘液间质中;间质可显著或少量粘液样变或玻璃样变,瘤细胞内含有原始血管腔,核分裂角,多形性及坏死少见,部分病例伴有梭形细胞血管内皮瘤改变,1例见破骨细胞样的多核巨细胞,免疫组织化学检测7例,7例波形蛋白均阳性,5例第八因子相关抗原,CD31,CD34阳性,2例细胞角蛋白弱阳性,1例CD68和a1-抗胰蛋白酶阳性,电镜观察1例见胞质内含丰富的微丝和少许的W－P小体,6例随访－8年,3例在原发部位有1或2次复发,但未见有转移,结论：上皮样血管内皮瘤是一种低度恶性的软组织肉瘤,其病因学尚不清楚,熟悉其形态特征对避免误诊为其他类似病变具具有重要意义。     

Primary thymic carcinoma

Summary A case of thymic carcinoma arising within a lymphocyte rich thymoma is reported. The undifferentiated carcinoma contained cellular elements resembling choriocarcinoma but could be differentiated there-from by positive staining for prekeratin antigen and an absence of staining for B-HCG antigen utilizing immunohistochemical techniques.Dedicated to Professor Karl Lennert, Kiel, on the occasion of his 65th birthday     

A new monoclonal antibody to human subcapsular thymic epithelial cells

Summary A monoclonal antibody, termed K-20, was generated against an anaplastic thymic carcinoma cell line, Ty-82. Subcapsular thymic epithelial cells of the thymus and blood vessels in various organs were shown to react with the K-20 monoclonal antibody by immunohistochemical staining. Immunofluorescent study revealed that various haematopoietic fresh cells and cell lines did not show any significant reactivity with K-20, except for one Epstein-Barr-virus-carrying lymphoma cell line (SP-50B). Western immunoblotting and affinity purification procedure revealed that K-20 was directed to a protein with a molecular weight of 28 kDa. K-20 is unique in its restrictive reactivity with human subcapsular thymic epithelial cells.     

Mouse mammary tumor virus production by thymic epithelial cells in vivo

Exogenous mouse mammary tumor viruses (MMTV) replicate in the mammary glands of infected females, and so infect the suckling pups. We have previously shown that the virus is rapidly disseminated to all the lymphoid organs, including the thymus. The present electron microscope immunohistochemical study describes the viral production site in the thymus. Viral buds and viral proteins were restricted to the thymus medullary epithelial cells. MMTV-encoded proteins were identified on the free viral particles and on the budding ones, the ribosomes, the membrane of the endoplasmic reticulum, and on the membrane of the medullary type II epithelial cell vacuolar network. The thymus medullary epithelial cells can thus integrate the virus and allow viral replication. The results support earlier results indicating that in some experimental conditions, epithelial cells may be involved in MMTV-induced negative selection by showing that thymic epithelial cells do express MMTV-encoded proteins.     

p53 Alterations in thymic epithelial tumours

 The prognosis of thymic epithelial tumours depends on malignant behaviour that cannot always be predicted on histological grounds. This study aimed at identifying a molecular marker that would be useful in overcoming the drawbacks of histopathology. Forty-four thymic epithelial tumours were analysed for alterations of the tumour suppressor gene p53 using immunohistochemistry (antibodies D0-1 and CM-1) and PCR-based single-strand conformation polymorphism and DNA sequencing. Histological and clinical evaluation and also p53 analysis revealed three major tumour groups: non-organotypic thymic carcinomas with frequent p53 alterations (7/9) and occurrence of p53 gene mutations (2/9); malignant thymomas with frequent p53 alterations but without p53 gene mutations (11/18); and benign thymomas with rare p53 alterations and without p53 gene mutations (2/17). In non-organotypic thymic carcinomas p53 was detected with both antibodies. In contrast, thymomas lacked immunoreaction with D0-1 suggesting alteration of the antibody-binding site. Overall immunohistochemical results correlated with clinical stages (P < 0.01), pathohistology (P < 0.01), and survival times (P < 0.05). We consider immunohistochemical p53 detection to be a useful new prognostic factor for the evaluation of thymic epithelial tumours. Received: 5 September 1996 / Accepted: 17 February 1997     

甲状腺内胸腺癌临床病理学分析

目的探讨甲状腺内胸腺癌(ITTC)的临床病理学特征、免疫表型和预后。方法回顾性分析ITTC患者的临床资料,包括一般临床资料、大体检查、组织学特征、免疫表型及EB病毒编码的小mRNA(EBER)原位杂交检测情况。结果纳入的9例患者肿瘤均为单发性病变,呈结节状。镜下可见肿瘤内大小不等的实性巢状、梁状结构,被间质致密的纤维组织分割成小叶状结构。肿瘤细胞呈多角形或短梭形,细胞界限不清。细胞质淡红染,细胞核圆形或卵圆形,空泡状,核仁明显。9例患者肿瘤均弥漫高表达CKAE1/AE3和CK5/6,不同程度表达CD5(弥漫表达或片状表达),8例患者表达CD117。5例患者肿瘤标本行EBER原位杂交检测,结果均为阴性。随访期间,1例患者失访;其余患者随访9~91个月,仅2例发生复发或转移。结论ITTC是一种罕见的甲状腺低度恶性肿瘤,具有独特的组织病理学特征和免疫表型,预后较好。CD5和CD117可作为ITTC诊断和鉴别诊断的标记物。     

Well-differentiated thymic carcinoma: a clinico-pathological study

Summary Well-differentiated thymic carcinoma (WDTC) is a recently described epithelial tumour of the thymus previously classified as cortical or predominantly epithelial thymoma. The authors have reviewed a series of 15 cases of WDTC with the aim of further defining the clinicopathological features of this neoplasm. Histologically, the number of lymphocytes was always low; perivascular spaces and epithelial palisading around blood vessels and/or along fibrous septa were prominent features; 6 cases (40%) were associated with areas of typical cortical thymoma. All cases showed slight to moderate cytological atypia and nuclear grooving was frequently detected. Mitotic activity was variable but usually low. Clinically, all but 3 cases (80%) were invasive at surgery; myasthenia gravis was present in 9 cases (60%); 5 patients (33.3%) died due to disease and 2 additional patients (13.3%) had tumor recurrence. Our study indicates that WDTC has fairly distinctive clinicopathological features and that it is histologically and histogenetically related to cortical thymoma. The definition “well-differentiated carcinoma” is justified because of low-grade cytological atypia and retention of some organotypical histological features, in a tumour otherwise often displaying aggressive and sometimes clear-cut malignant clinical behaviour.     

An immunohistochemical panel consisting of EZH2, C-KIT,and CD205 is useful for distinguishing thymic squamous cell carcinoma from type B3 thymoma

Type B3 thymoma and thymic squamous cell carcinoma (SqCC) often cause a diagnostic problem due to their histological similarities. The aim of this study is to identify EZH2 as a novel and powerful biomarker that can effectively distinguish thymic SqCC from type B3 thymoma, and find optimal combinations among 11 markers. A total of 53 patients, comprising 26 with type B3 thymoma and 27 with thymic SqCC, were allocated to the discovery or validation cohorts, and immunohistochemical staining was performed and analyzed. The expression level of each marker was scored, and receiver-operator characteristic curve analysis was performed to evaluate their diagnostic accuracies. This analysis identified EZH2, C-KIT, and CD205 as useful markers for distinguishing thymic SqCC, and a combined panel approach using them further improved diagnostic accuracy in both the discovery and validation cohorts. In the combined cohorts analysis, EZH2 was the single best marker with 88.9% sensitivity and 100% specificity [area under the curve (AUC)?=?0.967]. The sensitivity and specificity were 85.2% and 100% (AUC?=?0.962) for C-KIT, and 100% and 73.1% (AUC?=?0.844) for CD205. The combined panel had the highest sensitivity and specificity at 96.3% and 100%, which was significantly or marginally higher than those of EZH2, C-KIT, and CD205 alone (P?=?0.071, 0.034, and 0.005, respectively). The present findings indicate that EZH2 is useful as a novel diagnostic marker for distinguishing thymic SqCC and that the panel approach can be used as an effective differential diagnostic tool in daily practice.     

Primary thymic carcinoid with Cushing's syndrome

Summary In a 52-year-old Caucasian man osteopoikilosis had been misdiagnosed roentgenologically 2 years before his death. Gradually he developed Cushing's syndrome and ultimately superior vena caval obstruction. At autopsy a primary thymic carcinoid with extensive osteoblastic bone metastasis was found. Immunohistochemically the tumor was shown to be positive for adrenocorticotropic hormone (ACTH), cytokeratin (KL1), neuron-specific enolase, synaptophysin, chromogranin and glucagon. Remarkably the tumour was negative for serotonin despite high urinary hydroxyindolacetic acid levels. Bilateral hyperplasia of the adrenal cortex was found. The adenohypophysis showed a considerable reduction of ACTH-producing cells and numerous Crooke's cells with a characteristic immunohistochemical pattern.     

Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence

Members of the Wnt family of secreted glyco-lipo-proteins affect intrathymic T-cell development and are abundantly secreted by thymic epithelial cells (TECs) that create the specific microenvironment for thymocytes to develop into mature T-cells. During ageing, Wnt expression declines allowing adipoid involution of the thymic epithelium leading to reduced naïve T-cell output. The protein kinase C (PKC) family of serine-threonine kinases is involved in numerous intracellular biochemical processes, including Wnt signal transduction. In the present study, PKCδ expression is shown to increase with age and to co-localise with Wnt receptors Frizzled (Fz)-4 and -6. It is also demonstrated that connective tissue growth factor (CTGF) is a Wnt-4 target gene and is potentially involved in a negative feed-back loop of Wnt signal regulation. Down-regulation of Wnt-4 expression and activation of multiple repressor pathways suppressing β-catenin dependent signalling in TECs contribute to the initiation of thymic senescence.