胸腺瘤组织学分型与重症肌无力及临床分期关系

目的探讨胸腺瘤最新WHO病理分型与重症肌无力(MG)及临床分期之间的关系。方法回顾分析1980-2004年间74例因胸腺瘤行胸腺切除的患者,运用最新WHO分型标准(1999)对胸腺瘤进行重新分类,并运用统计软件对新的WHO组织学分型与MG的发生率及Masaoka临床分期之间的关系做进一步分析。结果(1)胸腺瘤A型2例,AB型23例,B1型4例,B2型27例,B3型16例,C型2例。其中B2型较AB、B1及B3型易合并MG(P<0.05),A型两例均合并MG,而C型则均未合并MG。(2)临床I期:1例,Ⅱ期:30例,Ⅲ期:38例,Ⅳ期:5例。新的WHO组织学分型与Masaoka分期之间关系密切(P<0.01)。结论新WHO组织学分型与胸腺瘤合并MG的发生率之间有一定关系,同时能反映其临床分期及评价患者的预后。     

伴淋巴样间质的微结节型胸腺瘤7例临床病理分析

目的 探讨伴淋巴样间质的微结节型胸腺瘤(MNT)的临床病理特征、诊断及鉴别诊断。方法 回顾性分析7例MNT患者的临床资料、病理学特征、免疫表型、治疗及预后，并复习相关文献。结果 7例MNT患者中，男性4例，女性3例；年龄44～71岁，平均年龄58岁。病灶均位于前纵隔，其中3例位于前上纵隔，1例位于左前中纵隔。2例为重症肌无力，4例无症状者胸部CT显示纵隔占位，1例因尿频尿急行前列腺穿刺示高级别上皮内瘤变(HGPIN),同时全身检查示纵隔占位。镜下2例为单纯MNT,1例合并胸腺囊肿，4例合并其他类型胸腺瘤(2例为AB型胸腺瘤，1例为B2型胸腺瘤，1例为A型胸腺瘤);7例均包膜完整，1例局灶包膜侵犯，其余6例包膜无肿瘤侵犯。镜下MNT示多灶分散或融合的小上皮样结节被大量淋巴细胞间质分隔，微结节由短梭形或卵圆形细胞组成，核染色质均匀，核仁不明显，未见核分裂和坏死。上皮细胞PCK、CK19、CK5/6表达阳性，且CD20、CD5、CD117表达阴性。淋巴间质细胞主要为CD20⁺/CD79a⁺B细胞，混有部分CD3⁺/CD5     

82例胸腺瘤新组织学分型与患者临床特征和预后的相关性分析

背景与目的:世界卫生组织(WHO)于1999年制定了新的胸腺瘤组织学分型标准。本研究探讨胸腺瘤WHO组织学分型与临床特征和预后的相关性。方法:回顾性分析82例经外科治疗的胸腺瘤患者的临床资料,经有经验的病理科医生按WHO组织学分型标准重新做出诊断,并结合患者的临床特征和预后进行分析。结果:胸腺瘤A型5例(6.1%),AB型21例(25.6%),B1型14例(17.1%),B2型12例(14.6%),B3型14例(17.1%),C型16例(19.5%)。根据Masaoka临床分期,Ⅰ期29例(35.4%),Ⅱ期13例(15.8%),Ⅲ期32例(39.0%),Ⅳa期8例(9.8%)。临床分期与组织学分型的相关性有显著性意义(χ2=47.29,P<0.001)。肿瘤外侵的程度与组织学分型的相关性也有显著性意义(χ2=30.78,P<0.001)。A﹑AB﹑B1和B2型胸腺瘤合计切除率较B3和C型胸腺瘤合计切除率高(84.6%vs.50.0%,χ2=11.29,P=0.002)。临床Ⅰ、Ⅱ、Ⅲ、Ⅳa期胸腺瘤切除术后5年生存率分别为100%、100%、69.5%和37.5%;10年生存率分别为88.1%、57.1%、47.5%和0。不同临床分期患者生存率的差异(log-rank=40.31,P<0.001)与组织学分型间生存率的差异(log-rank=16.0,P=0.007)均有统计学意义。结论:WHO组织学分型可在一定程度上反映胸腺瘤的生物学行为和临床特征,对临床诊断和治疗胸腺瘤有指导意义。     

胸腺瘤组织学分型与重症肌无力及临床分期关系

目的:探讨胸腺瘤最新WHO病理分型与重症肌无力(MG)及临床分期之间的关系。方法:回顾分析1980~2004年间 74例因胸腺瘤行胸腺切除的患者,运用最新WHO分型标准 (1999)对胸腺瘤进行重新分类,并运用统计软件对新的WHO组织学分型与MG的发生率及Masaoka临床分期之间的关系做进一步分析。结果:①胸腺瘤A型 2例,AB型 23例,B1型 4例,B2型 27例,B3型 16例,C型 2例。其中B2型较AB、B1及B3型易合并MG(P<0. 05),A型两例均合并MG,而C型则均未合并MG。②临床Ⅰ期: 1例,Ⅱ期: 30例,Ⅲ期: 38例,Ⅳ期: 5例。新的WHO组织学分型与Masaoka分期之间关系密切(P<0. 01)。结论:新WHO组织学分型与胸腺瘤合并MG的发生率之间有一定关系,同时能反映其临床分期及评价患者的预后。     

胸腺瘤组织中c-myc基因的表达及其意义

目的研究c-myc基因在胸腺瘤组织中的表达,探讨c-myc基因与胸腺瘤的发生发展、恶性程度的关系。方法应用免疫组织化学SP法,检测c-myc在41例胸腺瘤和18例非肿瘤胸腺组织中的表达,结合胸腺瘤WHO分型、Masaoka分期,研究c-myc基因在胸腺瘤各分型、分期中的表达情况。结果c-myc在胸腺瘤中的阳性表达率为63.4%,在非肿瘤胸腺组织中的阳性表达率为16.7%,两者间有统计学差异(P<0.01)。c-myc在良性胸腺瘤(A/AB型)和恶性胸腺瘤(B1~B3型)中的表达分别为30.0%和74.2%,两者有统计学差异(P<0.05)。c-myc在非侵袭性胸腺瘤(Ⅰ期)与侵袭性胸腺瘤(Ⅱ~Ⅳ期)中的表达分别为33.3%和75.9%,两者有统计学差异(P<0.05)。结论c-myc与胸腺瘤的发生发展有关;与胸腺瘤的恶性程度、侵袭性有关。     

胸腺瘤合并重症肌无力的临床病理分析及手术治疗

目的探讨胸腺瘤最新WHO病理分型与重症肌无力(myasthenia gravis,MG)发生率的关系以及手术方式对预后的影响。方法回顾分析2001年10月—2010年7月42例胸腺瘤合并MG行胸腺切除术患者的临床资料,应用胸腺瘤的最新WHO分型标准及传统方法对胸腺瘤进行分类,采用胸骨正中切口24例,前胸切口13例,后外侧切口5例,观察MG发生率及手术预后。结果 (1)WHO病理分型A型+AB型良性病例较多,B型恶性病例较多,体现出A型及AB型胸腺瘤良性的特点。(2)B3型较A型及AB型易合并MG。B3型胸腺瘤合并MG的手术危象发生率比A型+AB型组、B1+B2型组高,(3)全组死亡7例,其余均缓解或治愈。胸腺瘤病理分期和手术方式为影响预后的主要因素。结论胸腺瘤最新WHO病理分型对于区别良、恶性肿瘤及预后有指导意义,结合Masaoka病理分期对提示术后MG危象有一定的应用价值。治疗原则应尽可能广泛切除肿瘤,术后根据具体情况辅以放疗、化疗。手术方式、病理分期对预后影响较大。     

胸腺瘤组织学分型与重症肌无力及临床分期关系(英文)

目的探讨胸腺瘤最新 WHO 病理分型与重症肌无力(MG)及临床分期之间的关系。方法回顾分析1980～2004年间74例因胸腺瘤行胸腺切除的患者,运用最新 WHO 分型标准(1999)对胸腺瘤进行重新分类,并运用统计软件对新的 WHO 组织学分型与 MG 的发生率及 Masaoka 临床分期之间的关系做进一步分析。结果 (1)胸腺瘤 A 型2例,AB 型23例,B1型4例,B2型27例,B3型16例,C 型2例。其中 B2型较 AB、B1及 B3型易合并 MG(P<0.05),A 型两例均合并 MG,而 C 型则均未合并 MG。(2)临床Ⅰ期:1例,Ⅱ期:30例,Ⅲ期:38例,Ⅳ期:5例。新的 WHO 组织学分型与 Masaoka 分期之间关系密切(P<0.01)。结论新 WHO 组织学分型与胸腺瘤合并 MG 的发生率之间有一定关系,同时能反映其临床分期及评价患者的预后。     

胃炎症性肌纤维母细胞瘤6例CT征象分析

摘 要：［目的］ 探讨胃炎症性肌纤维母细胞瘤(IMT)的CT表现。［方法］ 回顾性分析6例胃IMTs的CT检查资料,所有病例均经外科手术病理证实。［结果］ 肿瘤发生部位以胃体为最常见（5/6）,其次为胃底（1/6）,无发生在胃窦的病例;肿瘤呈肿块结节型、胃壁增厚型或肿块结节伴邻近胃壁增厚型,瘤体大小不一,呈软组织密度,均匀或不均匀,瘤体内可出现小的坏死灶,钙化可见但较少见;动态增强扫描除坏死灶无强化外,肿瘤强化均较明显;肿瘤边界大部欠清,胃浆膜层、胃周脂肪间隙可受浸润,尚未发现胃周、腹膜后等淋巴结肿大,亦未发现其他脏器转移等征象。［讨论］ 胃IMT的CT征象较多,有一定的特征性,但目前确诊上仍需依靠病理。     

不同CT征象对胸腺瘤与常见纵隔恶性肿瘤的诊断及鉴别诊断

目的:分析不同CT征象对胸腺瘤与常见纵隔恶性肿瘤的诊断及鉴别诊断临床价值。方法:选择2011年3月-2014年6月期间我院收治的经手术及穿刺病理及临床随访证实的90例纵隔肿瘤患者,其中非侵袭性胸腺瘤30例,侵袭性胸腺瘤28例,纵隔恶性肿瘤32例。所有肿瘤患者均行平扫及增强扫描,利用MSCT的动态增强及MPR成像,分析三种类型纵隔肿瘤的CT图像特征,比较三种肿瘤基本特点的差异性。结果:经过MSCT的动态增强技术及MPR技术成像分析,非侵袭性胸腺瘤患者CT成像的形态规则28例,欠规则2例,边缘光滑27例,欠光滑3例,毛糙0例,密度均匀27例,欠均匀3例,与侵袭性胸腺瘤和纵隔恶性肿瘤CT成像的形态是否规则、边缘是否光滑、密度是否均匀的差异性比较明显,两两比较均具有显著性差异（P<0.05）。非侵袭性胸腺瘤患者CT成像的MCI形态凸出型27例,平坦型3例,灌注型0例,周围脏器间隙清晰29例,部分层面清晰1例,间隙不清晰0例,周围组织分界清晰30例,分界不清0例,与侵袭性胸腺瘤和纵隔恶性肿瘤CT成像的MCI形态类型、周围脏器间隙是否清晰以及周围组织分界是否清晰差异性显著,两两比较具有明显差异性（P<0.05）。经过MSCT的动态增强技术及MPR技术分析,非侵袭性胸腺瘤患者CT成像经过强化,强度变化不明显24例,轻度强化6例,不均匀强化0例,伴有胸腔积液1例,无胸腔积液29例,纵隔、腋窝与颈部基本无患者具有肿大淋巴结,与侵袭性胸腺瘤和纵隔恶性肿瘤CT成像的强化特点、是否伴有胸腔积液、有无肿大淋巴结等差异性显著,两两比较具有明显差异性（P<0.05）。结论:利用MSCT动态增强技术和MPR技术,能够明显区分非侵袭性胸腺瘤、侵袭性胸腺瘤与纵隔恶性肿瘤,为临床诊断提供了技术支持,是一种值得推广的区分三种类型肿瘤的鉴别方法。     

影响脑膜瘤术后复发的影像相关因素分析

目的:探讨脑膜瘤切除术后复发的影像相关因素。方法:对20例复发性和98例非复发性脑膜瘤的临床资料、CT、MRI影像进行了对比分析。结果:蕈形及结节形者肿瘤复发率显著高于圆形者(P<0.01);中度和重度水肿组复发率显著高于无水肿和轻度水肿组(P<0.05);无钙化肿瘤复发率显著高于有钙化肿瘤(P<0.01);骨质溶解肿瘤复发率显著高于骨质增生肿瘤(P<0.01);有肿瘤内坏死复发率显著高于无肿瘤内坏死肿瘤(P<0.01);非均一强化肿瘤复发率显著高于有均一强化肿瘤(P<0.01)。结论:CT、MRI表现为蕈形及结节形者、严重瘤周水肿、无钙化、周围骨质溶解、肿瘤内坏死及肿瘤非均一强化者具有较高的术后复发率。复发率的高低顺序依次为周围骨质溶解、肿瘤内坏死、蕈形及结节形者、肿瘤非均一强化、无钙化、严重瘤周水肿。其中有周围骨质溶解者复发率远远高于其它(P<0.01)。     

Relationship Between Computed Tomography Manifestations of Thymic Epithelial Tumors and the WHO Pathological Classification

Objective: To explore the relationship between computed tomography (CT) manifestations of thymoma andits WHO pathological classification. Methods: One hundred and five histopathologically confirmed cases werecollected for their pathological and CT characteristics and results were statistically compared between differentpathological types of thymoma. Results: Tumor size, shape, necrosis or cystic change, capsule integrity, invasionto the adjacent tissue, lymphadenopathy, and the presence of pleural effusion were significantly different betweendifferent pathological types of thymomas (P <0.05). Type B2, B3 tumors and thymic carcinomas were greater insize than other types. More than 50% of type B3 tumors and thymic carcinomas had a tumor size greater than10 cm. The shape of types A, AB, and B1 tumors were mostly round or oval, whereas 75% of type B3 tumorsand 85% of thymic carcinomas were irregular in shape. Necrosis or cystic change occurred in 67% of type B3thymomas and 57% of thymic carcinomas, respectively. The respective figures for capsule destruction were 83%and 100% . Increases in the degree of malignancy were associated with increases in the incidence of surroundingtissue invasion: 33%, 75%, and 81% in type B2, type B3, and thymic carcinomas, respectively. Pleural effusionoccurred in 48% of thymic carcinomas, while calcification was observed mostly in type B thymomas. Conclusions:Different pathological types of thymic epithelial tumors have different CT manifestations. Distinctive CT featuresof thymomas may reflect their pathological types.     

The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients

BACKGROUND: Although the histologic classification of thymic epithelial tumors has been confusing and controversial, an agreement on the universal classification system for thymic epithelial tumors was achieved by the World Health Organization (WHO) in 1999. The authors previously reported that the WHO histologic classification system reflects invasiveness and immunologic function of thymic epithelial tumors. In this subsequent study, they examined the prognostic significance of this classification system. METHODS: Clinical features as well as postoperative survival of patients with thymoma, but not thymic carcinoma, were examined with reference to WHO histologic classification based on an experience with 273 patients over a 44-year period. RESULTS: There were 18 type A tumors, 77 type AB tumors, 55 type B1 tumors, 97 type B2 tumors, and 26 type B3 tumors. In patients with type A, AB, B1, B2, and B3 tumors, the respective proportions of invasive tumor were 11.1%, 41.6%, 47.3%, 69.1%, and 84.6%; the respective proportions of tumors with involvement of the great vessels were 0%, 3.9%, 7.3%, 17.5%, and 19.2%; and the respective 20-year survival rates were 100%, 87%, 91%, 59%, and 36%. According to the Masaoka staging system, the 20-year survival rates were 89%, 91%, 49%, 0%, and 0% in patients with Stage I, II, III, IVa, and IVb disease, respectively. By multivariate analysis, the Masaoka staging system and the WHO histologic classification system were significant independent prognostic factors, whereas age, gender, association with myasthenia gravis, completeness of resection, or involvement of the great vessels were not significant independent prognostic factors. CONCLUSIONS: This study showed that histologic appearance reflects the oncologic behavior of thymoma when the WHO classification system is adopted. The WHO classification system may be helpful in clinical practice for the assessment and treatment of patients with thymoma.     

Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to world health organization histologic classification system

BACKGROUND AND OBJECTIVES: The aim of this study was to clarify the significance of surgical treatment for recurrent thymic epithelial tumors with reference to the World Health Organization (WHO) histological classification system. PATIENTS: Among 67 patients with tumor recurrence, 22 underwent a re-resection. There were 1 patient with a type AB tumor, 5 with type B1 tumors, 10 with type B2 tumors, 5 with type B3 tumors, and 1 with a carcinoma. RESULTS: The 10-year survival rate following the initial resection was 70% in patients who underwent a re-resection and 35% in those who did not. The average intervals from the initial resection to re-resection were 10.3, 7.8, 6.0, 2.4, and 2.6 years for patients with type AB, B1, B2, B3 tumors, and carcinoma, respectively. The patient with a type AB tumor was alive at 2.4 years after re-resection, 12.7 years after the initial resection. The 5-year survival rates following re-resection in the patients with type B1, B2, and B3 tumors were 100, 56, and 60, respectively. The patient with a carcinoma died as a result of the tumor 2 years after re-resection. CONCLUSION: WHO histological classification indicates the outcome of surgical treatment for recurrent thymic epithelial tumors.     

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1–B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.     

Diagnostic and clinical significance of KIT(CD117) expression in thymic epithelial tumors in China

Aims: To study KIT (CD117) expression in thymic epithelial tumors in China, and investigate diagnosticand clinical significance. Material and Methods: Thymic epithelial tumors (TETs) from 102 patients (3 type A,29 type AB, 5 type B1, 22 type B2, 29 typeB3 and 16 thymic carcinomas) were examined. Immunohistochemicalstaining with an antic-kit monoclonal antibody was performed on a tissue microarray. Relationships betweenKIT positive expression and the TET clinical characteristics (WHO histologic classification and Masaoka stagesystem) were analysed. Results: The KIT positive expression rate was significantly higher in thymic carcinoma(60%, 9/16) than in thymoma (8%, 7/86), a strong correlation being found with the WHO classification, but notthe Masaoka tumor stage. The overall survival for patients with KIT positive lesions was significantly worse.Conclusions: KIT is a good molecule marker to differentially diagnose thymic carcinoma from thymoma, whilealso serving as a predictor of prognosis for TETs. Further research into KIT mutations in Chinese TETs shouldbe conducted to assess the efficacy of targeted therapy.     

胸腺上皮性肿瘤中TTF1、Ki-67的表达与WHO分型的关系及临床意义

目的 观察TTF1及Ki-67在胸腺上皮性肿瘤(Thymic epithelial tumors,TET)中的表达情况,探讨其与WHO分型的关系及二者的相关性。方法 收集59例TET标本,其中诊断一致的51例,不一致8例。应用免疫组化技术检测TTF1及Ki-67在诊断一致的 51例TET及30例胸腺增生组织中的表达情况,并分析其与临床病理参数之间的关系。结果 在诊断不一致的8例TET中,4例与AB型有关。在诊断一致的51例TET中,TTF1及Ki-67在TET中的表达均显著高于胸腺增生组(P＜0.05)。TTF1仅在AB型胸腺瘤中表达(11/15),其表达与WHO分型有关。Ki-67标记指数从A型到胸腺癌逐渐增加,且在A型与胸腺癌的表达范围不重叠,其表达与WHO分型及MasaoKa分期均有关。同时TTF1及Ki-67在TET中的表达没有相关性。结论 TTF1是AB型胸腺瘤相对特异性的标记;Ki-67不仅对A型与胸腺癌中的区分有帮助,同时具有很好的指示预后的价值。     

单一医生组原发性纵隔肿瘤外科治疗的长期随访

  目的   总结单一医生组原发性纵隔肿瘤外科治疗的长期随访。   方法   数据来自北京大学肿瘤医院2000年1月至2014年1月的前瞻性数据库。分析纵隔肿瘤数据库中以根治切除为目的患者的远期生存。   结果   本组常见肿瘤依次为胸腺上皮肿瘤95例（50%）,神经源性肿瘤26例（13.7%）,纵隔生殖细胞肿瘤26例（13.7%）。全组患者行R0切除者179例（94.2%）,R2切除者8例（4.2%）,单纯探查者3例（1.6%）,术后30d内死亡2例。胸腺上皮肿瘤1、3和5年生存率分别为95%、92.7%和85.7%。根据Masaoka-Koga分期,Ⅰ、Ⅱ、Ⅲ和Ⅳ期胸腺上皮肿瘤的5年生存率分别为100%、82.1%、90%和37.5%。多因素分析显示Masaoka-Koga分期是胸腺上皮肿瘤手术后独立预后因素。A+AB+B1型与B2+B3型胸腺瘤5年生存率分别为88.6%与76.9%,差异具有统计学意义（P < 0.05）。神经源性纵隔肿瘤多为良性,完整切除后均长期生存。   结论   纵隔肿瘤组织学复杂,根据其来源、性质、部位及大小来决定治疗。虽然本组患者生存良好,但单一医生组很难做到前瞻性,大样本研究。因此,对纵隔肿瘤尤其是胸腺上皮肿瘤亟需大样本,多中心合作的前瞻性研究,以找到合理的治疗方式。      

Surgical outcomes and reevaluation of treatment strategies for thymomas

Improved histological typing systems for thymic tumors and advances in induction and adjuvant therapy have created the need to reevaluate strategies for the management of thymoma. We retrospectively studied 73 patients with completely resected thymomas unassociated with myasthenia gravis. The World Health Organization (WHO) histologic classification, clinicopathological features and surgical outcomes were analyzed. Overall survival was 66.2% at 10 years, and the median survival time was 169 months. According to the Masaoka staging system, overall survival rates at 10 years were 94.7% in stage I, 76.1% in stage II, 30% in stage III and 0% in stage IV. In the WHO classification, overall survival rates at 10 years were 91.9% in types A and AB, 50.9% in type B2 and not achieved in type B3. The disease-free interval was slightly shorter in patients with B2 and B3 disease than in those with type A, AB and B1 disease. Advanced thymomas were significantly associated with type B2 and B3 (p<0.01). In stage III and IV disease, adjuvant or neoadjuvant therapy was associated with better survival as compared to no adjuvant therapy (p=0.07). On multivariate analysis, Masaoka stage III and IV disease and extended thymectomy indicated significant, negative and independent risk factors for survival (p<0.01). Masaoka stage I and II thymomas or WHO type A and AB thymomas have favorable prognoses and do not require postoperative adjuvant therapy. Patients with stage III and IV thymomas require additional therapy after surgery.     

Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas

Thymomas are thymic epithelial tumors. Because most of them are rich in nonneoplastic T-cells, recurrent genetic aberrations have been reported only in the rare, lymphocyte-poor WHO types A, B3, and C. We have now investigated virtually the whole spectrum of thymomas, including the commoner types AB and B2, microdissecting or culturing neoplastic cells from these lymphocyte-rich thymomas and applying 41 microsatellite markers covering 17 loci on 10 chromosomes. In 28 cases, comparative genomic hybridization data were available. Apart from type A, there was striking heterogeneity between thymomas. Allelic imbalances were seen in 87.3% of the 55 cases, and MSI in 9.9%. Losses of heterozygosity (LOHs) were much the commonest aberration. Overall, they were most prevalent at four regions on chromosome 6. Aberrations elsewhere, affecting mainly 8p11.21 and 7p15.3, suggested a cortical footprint because they recurred only in the thymopoietically active type AB and B thymomas. LOHs were also seen at the adenomatous polyposis coli (APC) locus (5q21-22) in subsets of these thymomas, whereas combined LOHs at the APC, retinoblastoma (13q14.3), and p53 (17p13.1) loci were confined to a subset of B3 thymomas that had possibly evolved from APC-hemizygous B2 thymomas by tumor progression; indeed, thymomas combing B2 plus B3 features are common. Notably, some AB and B thymomas shared LOHs despite their nonoverlapping morphology and different clinical behavior. Finally, allelic imbalances at 8p11.21 and 16q22.1 (CDH1) were significantly more frequent in stage IV metastatic thymomas. We conclude that the WHO-defined histological thymoma types generally segregate with characteristic genetic features, type A thymomas being the most homogeneous. Many findings support the view that B2 and B3 thymomas form a continuum, with evidence of tumor progression. However, other findings imply that types A and AB are biologically distinct from the others, any potential invasiveness being severely restricted by a medullary commitment in the precursor cell undergoing neoplastic transformation.     

Clusters of chromosomal imbalances in thymic epithelial tumours are associated with the WHO classification and the staging system according to Masaoka

Using comparative genomic hybridisation, we investigated chromosomal imbalances in 28 cases of thymic epithelial neoplasms including type A, B2, B3, the A component of type AB and different subtypes of type C thymoma. To identify different patterns of chromosomal aberrations associated with the biological behaviour and the histological diversity of thymomas, a hierarchical cluster analysis of 65 cases was performed. The here-reported Comparative Genomic Hybridisation (CGH) data (28 cases) of partly uninvestigated tumour subtypes were pooled with previously published data of chromosomal imbalances of 37 thymomas (Zettl et al. [Am J Pathol 2000;157:257-66]). The analysis of 278 chromosomal subbands yielded 2 main clusters. The first main cluster was characterised by gains of the chromosomal arm 1q, consisted only of type C and B3 thymomas and was further subdivided into 2 subgroups. To the first subgroup only thymomas were attributed, which, in addition to gains of the chromosomal arm 1q, showed losses on 6q and 16q, whereas tumours belonging to the second subgroup exhibited no further recurrent chromosomal alterations. The second main cluster was formed by a heterogeneous group of thymoma types (types A, AB, B2, B3 and C), showing no specific pattern of chromosomal imbalances. In 19 thymomas, no chromosomal imbalances could be detected (3 type B2 and 5 type A thymomas of our study as well as 11 type A thymomas investigated by Zettl et al., Am J Pathol 2000;157:257-66). Chromosomal imbalances were more frequent in type C thymomas than in other subtypes. The distribution of tumour stages according to Masaoka (p = 0.003) and the World Health Organisation (WHO) classification (p < 0.0001) was significantly different in the clusters and subgroups obtained. The groups reflect the staging system and the WHO classification and show that type B3 and type C carcinomas have a strong relationship concerning their chromosomal imbalances. Furthermore, chromosomal imbalances detected in some type A thymomas might be responsible for the aggressive behaviour described in a few cases of this thymoma subtype.