Liver metastasis of thymoma--report of two cases

We experienced two cases of liver metastasis resulting from thymoma, which is reported to be rare in Japan. Case 1 was a 57-year-old man who was admitted because of hepatomegaly. US, CT and angiography revealed multiple tumors in the liver which were thought to be liver metastasis from an unknown origin. He died of cardiac tamponade one year later. An autopsy revealed thymoma with metastasis to the liver, lung and pericardium. Case 2 was a 32-year-old female who visited our hospital complaining of right hypochondriac pain, US detected several large hyperechoic masses in the liver. A us-guided liver biopsy confirmed metastasis from thymoma. Histological tests of the liver of these two cases showed epithelial type of thymoma.     

卵巢上皮性肿瘤血管生成活性的研究

探讨不同性质卵巢上皮性肿瘤的血管生成活性 ,并探讨血管生成与卵巢癌临床分期和病理分级的关系。方法　采用免疫组化LSAB法。结果　 74例卵巢上皮性肿瘤中 ,良性 16例、交界性 12例、恶性 46例。三组肿瘤中 ,其微血管密度依次升高。卵巢癌组 ,晚期卵巢癌微血管密度高于早期 ,中、低分化组卵巢癌微血管密度高于高分化组。结论　血管生成在卵巢癌的发生发展中起重要作用 ,微血管密度可作为判断卵巢肿瘤恶性度的一项指标。     

The distribution of epithelial membrane antigen in thymic epithelial neoplasms.

Thymic carcinomas arising within a thymoma have been reported, but the relationship between thymoma and thymic carcinoma is poorly understood. Epithelial membrane antigen (EMA) is known to be an effective marker for establishing the epithelial nature of neoplastic cells, and it is reported that staining of tumors is clearly related to the degree of tumor differentiation. Eighty-one thymomas (59 noninvasive, 22 invasive) and 14 thymic carcinomas were studied immunohistologically using antiepithelial membrane antigen (anti-EMA) monoclonal antibody. Thymic carcinomas tended to express much larger quantities of EMA than thymomas, and instances of EMA-positive thymoma were seen significantly more often in invasive thymomas than in noninvasive ones (P < 0.05). However, EMA positivity was also associated with gland-like structures, which were not necessarily associated with malignant disease. Nevertheless, in view of the concept that thymoma and thymic carcinoma show a similar cellular differentiation, EMA-positive epithelial cells in thymoma with no relation to gland-like configurations might represent a pool of cells having a latent potential for malignant disease and might be transformed into thymic carcinoma cells under certain conditions. Immunolabeling for EMA appears to be a useful tool for determining the degree of malignant disease among thymic epithelial neoplasms.     

Follicular dendritic cell sarcoma of the neck: report of two cases complicated by pulmonary metastases

BACKGROUND: Follicular dendritic cell (FDC) sarcoma is an uncommon neoplasm occurring primarily in lymph nodes but also in extranodal sites. A correct diagnosis can be difficult to make, especially in the latter sites. METHODS: Two patients with FDC sarcoma of the cervical soft tissues that metastasized to the lungs are reported. Both were initially misdiagnosed as having CASTLE (carcinoma showing a thymus-like element). Additional immunohistochemical stains were performed. RESULTS: The primary tumors showed jigsaw puzzle-like lobulation resembling thymic epithelial tumor and consisted of spindly cells arranged in fascicles, whorls, and a storiform pattern. The spindly cells had indistinct cell borders, vesicular nuclei, and distinct nucleoli. Perivascular spaces were present. Lymphocytes were sprinkled throughout the tumor in one case but were sparse in the other. The metastatic deposits in the lungs appeared 27 and 2 years, respectively, after the initial presentation and were histologically similar to the original tumors. The FDC nature of the primary and metastatic tumors was confirmed by positive staining with CD21/CD35 cocktail and CD23 and by negative staining for cytokeratin. In one case, in direct continuity with the main tumor, there was a lobulated lesion composed of small lymphocytes punctuated by large cells with vesicular nuclei, histologically reminiscent of thymoma. The large cells were shown by immunohistochemistry to represent FDCs forming complex interconnecting meshworks. It is unclear whether this contiguous mass represents a precursor lesion or an unusual-looking component of the neoplasm. CONCLUSIONS: FDC sarcoma can look deceptively like a thymic epithelial tumor histologically. A correct diagnosis requires a high index of suspicion and immunohistochemical evaluation. The tumor shows a propensity to metastasize to the lungs, which can be delayed until more than 20 years after initial presentation.     

心包原发性恶性间皮瘤的临床特点及病理观察

目的：了解心包原发性恶性间皮瘤（primary malignant pericardial mesothelioma,PMPM）的临床病理特点。方法：收集2例PMPM患者的临床资料。切除组织HE染色光镜观察,免疫组织化学做CKp、CK18、EMA、MC、Vimentin、CEA、Calretinin、TTF1、Tg标记。结果：2例PMPM是以上皮细胞为主型,呈乳头状和腺管样排列。免疫组织化学标记瘤组织CKp、CK18、Vimentin、Calretinin阳性。MC例1阳性,例2阴性,EMA例1阴性,例2阳性。临床改变似心包炎和心包积液。结论：恶性心包间皮瘤临床改变似心包炎,只有病理检查才能确诊。     

Clinical and biological characteristics of clear cell carcinomas of the ovary in FIGO stages I-II

Clear cell carcinoma of the ovary is considered to be a specific subtype among the epithelial ovarian malignancies. To characterize clear cell carcinomas in early FIGO stages (I-II) with regard to clinical and biological properties, a retrospective study was performed to compare these tumors with other histological subtypes. From a complete series of 226 patients with epithelial ovarian carcinomas in FIGO stages I-II, 28 patients with clear cell carcinomas were selected and the clinical and biological characteristics of these tumors were compared with the remaining non-clear cell carcinomas. All patients underwent primary staging laparotomy followed by adjuvant radiotherapy or chemotherapy. The apoptosis regulators p53, bcl-2 and bax, and the growth factor receptors EGFR and HER-2/neu were analyzed by immunohistochemical techniques and DNA analysis was performed by flow cytometry. Clear cell carcinomas stained negative for p53 significantly more often than other histological subtypes. Positive EGFR staining was seen more frequently in serous carcinomas than in the clear cell carcinomas. Aneuploid DNA status was seen more frequently in clear cell carcinomas than in other histological subtypes and tetraploid tumors made up 50% of the non-diploid tumors. Clear cell tumors were frequently (64%) found in FIGO stages IC and IIC and this was more common than for non-clear cell tumors. No difference was found in the rate of tumor recurrences or survival for patients with clear cell and non-clear cell carcinomas. Clear cell carcinomas of the ovary should be regarded as a separate entity among the epithelial ovarian carcinomas and they differ with regard to both clinical and biological characteristics when compared with non-clear cell tumors.     

Three cases of multiple thymoma with a review of the literature

Three cases of patients with synchronous multiple thymoma are reported. Two patients had two thymomas each and the remaining patient had three. The thymomas in each patient all displayed similar histological findings, of which the WHO histological classification were type B2, A and B1, respectively. With a modified Masaoka staging system, the thymomas were determined to be stages II-1 and I in patient 1, one of stage III and two of stage I in patient 2, and two of stage II-1 in patient 3. We reviewed nine reported cases of multiple thymoma in which histological findings were provided and discuss whether they developed from multi-centric origin or from intra-thymic metastasis.     

Increased expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 is correlated with poor prognostic variables in patients with thymic epithelial tumors

BACKGROUND: A distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma. METHODS: Tumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital. Three-micrometer-thick, formalin-fixed, paraffin-embedded tissue sections were immunostained using specific antibodies against MMP-2, MMP-9, TIMP-1, and TIMP-2. RESULTS: MMP-2 expression was detected in 30 tumors (71%), and TIMP-2 expression was detected in 31 tumors (74%). MMP-9 expression was detected in 22 of 36 tumors (61%), and TIMP-1 expression was detected in only 7 tumors (19%). MMP-2 and TIMP-2 expression levels were very low (10% and 0%, respectively) in noninvasive tumors but were very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial tumors, the more progressive the clinical stage of tumor, the higher the strongly positive rate of MMP-2 and TIMP-2 expression. There was no correlation between positivity for MMP-9 and stage. Twenty-five percent of Type AB thymomas and 50% of Type B1 thymomas expressed MMP-2 and TIMP-2. Most of Type A, Type B2, Type B3, and Type C thymomas expressed MMP-2 and TIMP-2. There were significant differences in disease-free survival at 5 years between patients without and with MMP-2 expression (91% vs. 55%, respectively) and patients without and with TIMP-2 expression (100% vs. 53%, respectively). CONCLUSIONS: MMP-2 and TIMP-2 are key enzymes for invasiveness of thymic epithelial tumors. The expression of these proteins can predict a poor outcome in patients with thymoma.     

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。     

An ultrastructural study of nine thymomas.

Nine thymomas, a normal adult thymus, and tissue culture of one thymoma were studied ultrastructurally. The histologic types of thymoma included lymphocytic, epithelial, mixed and spindle cell varieties. Two of the tumors were invasive and one was associated with myasthenia gravis. Despite the histologic dissimilarities, the complex anatomic interrelationships involving lymphocytes, epithelial cells, and blood vessels as seen in the thymus tended to be preserved in all but one of the thymomas. The exception was the spindle-cell thymoma which contained only rare lymphocytes and simpler vascular structures. The findings include variations in the frequency of demosomes and cytoplasmic fibrils of the epithelial cells, the occasional presence of lymphocytes within the laminated venules, and the unusual finding of a gland-like structure in one of the tumors. Correlations between ultrastructural changes and clinical behavior could not be made.     

Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases

Two hundred thymomas, surgically treated between 1955 and 1982 at the Marie Lannelongue Surgical Center, were subjected to statistical analysis, comparing clinical stages and histologic types and relating them to survival. Clinical stages were defined as follows. Stage I: no invasiveness, total excision; Stage II: localized invasiveness (no more than two mediastinal structures); Stage III: largely invasive, with or without distant tumorous grafts, lymph node deposits, or metastases. Four histologic types were retained: (1) spindle or oval cell type thymoma, (2) lymphocyte-rich thymoma, (3) differentiated epithelial thymoma, and (4) undifferentiated epithelial thymoma. Invasiveness remained a major prognostic factor, but the degree of invasion did not affect the survival rate or always justify radical surgery. Thus, the survival rate dropped from 85% at 5 years and 80% at 10 years in noninvasive tumors to 50% and 35%, respectively, in invasive tumors, but without significant difference between moderately invasive Stage II and largely invasive Stage III tumors. Histologic typing indicated a good correlation between the degree of differentiation of the tumors and prognosis. The survival rates were 80% at 5 years and 75% at 10 years for spindle cell type 1 and lymphocyte-rich type 2 thymomas, 75% at 5 years and 50% at 10 years for differentiated epithelial type 3, and nil at 5 years for undifferentiated type 4 thymomas. Although invasiveness often paralleled histologic typing, they appeared as two distinct parameters with separate prognostic significance, particularly in differentiated and undifferentiated epithelial tumors. One hundred five patients had myasthenia gravis and 14 had another autoimmune disease. The associated syndromes were no longer an adverse factor in the prognosis of thymoma.     

Activation of matrix metalloproteinase-2 is correlated with invasiveness in thymic epithelial tumors

BACKGROUND AND OBJECTS: Matrix degradation, which is a critical event in the process of tumor invasion and metastasis, is considered to be caused by the action of proteolytic enzymes. METHODS: We examined the gelatinolytic activity of matrix metalloproteinase (MMP)-9, and the activity of active and inactive forms of MMP-2 in five thymi, five noninvasive thymomas, eight invasive thymomas, and five thymic carcinomas by quantitative gelatinolytic zymography. RESULTS: The gelatinolytic activity of active MMP-2 in five thymi was zero. The mean gelatinolytic activity of active MMP-2 was 0.020 +/- 0.015 in noninvasive thymoma, 0.084 +/- 0.098 in invasive thymoma and 0.246 +/- 0.194 in thymic carcinoma. The gelatinolytic activity of active MMP-2 correlated with the invasiveness of thymic epithelial tumors (Spearman rank correlation: r-value = 0.532). The gelatinolytic activity of active MMP-2 in three thymoma cases with microscopic capsular invasion was the same as that of noninvasive thymoma. When thymoma cases showing microscopic capsular invasion were classified into the "macroscopically noninvasive thymoma" group, the gelatinolytic activity of active MMP-2 correlated with the invasiveness of thymic epithelial tumors (Spearman rank correlation: r-value = 0.621). CONCLUSIONS: The gelatinolytic activity of active MMP-2 significantly correlated with the invasiveness in thymic epithelial tumors. J. Surg. Oncol. 2001;76:169-175.     

胸腺非典型性类癌的临床病理及免疫组化表型

目的:了解胸腺非典型性类癌的临床病理特征。方法:收集2例胸腺非典型性类癌的临床资料,手术切除组织光镜切片观察,另作10项免疫组织化学标记:CKp,EMA,Ki-67,CD3,CD20,CD5,TdT,NSE,CgA,Syn。结果:2例胸腺非典型性类癌均为男性,纵膈肿瘤,由小园形细胞构成。瘤细胞CKp、EMA、NSE、CgA、Syn阳性,CD3、CD5、CD20、TdT阴性,Ki-67核阳性细胞指数>20%,肿瘤有显著坏死。结论:非典型性类癌是一种罕见的胸腺肿瘤,诊断靠病理组织学和免疫组织化学标记,手术切除为主要治疗方法。     

Surgical,Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Clinical Practice Guideline

IntroductionThe aim of this guideline was to provide recommendations for the most effective therapy for patients with thymic epithelial tumors, including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETs). This guideline is intended to be used by all health care professionals managing patients with thymic epithelial tumors.MethodsThe guideline was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of the evidence, expert consensus, and formal internal and external reviews.ResultsEvidence-based recommendations were developed to improve the management of patients with thymic epithelial tumors. The guideline includes recommendations for surgical, radiation, and systemic treatments for patients with thymoma, thymic carcinoma, and thymic NETs separated by stage of disease using the TNM staging system. Recommendations for patients with thymic NETs were endorsed from the 2021 National Comprehensive Cancer Network Neuroendocrine and Adrenal Tumors Guideline.ConclusionsThis guideline reflects the new staging system for patients with thymoma and thymic carcinoma and includes supporting evidence from the best available studies.     

卵巢癌组织SEMA3F表达及甲基化初步研究

目的研究神经轴突导向分子SEMA3F在不同卵巢上皮肿瘤组织的表达及其与上皮性卵巢癌各临床病理参数及预后的关系,并初步探讨SEMA3F启动子区甲基化与上皮性卵巢癌的关系。方法选取2004-12-01-2008-12-30南通大学附属医院收集的95例卵巢癌、30例交界性卵巢上皮肿瘤、30例良性卵巢上皮肿瘤和10例正常卵巢组织标本,采用免疫组织化学方法检测SEMA3F的表达。应用半定量RT-PCR法检测2013-05-01-2013-12-31南通大学附属医院收集的12例新鲜上皮性卵巢癌、10例新鲜良性卵巢上皮肿瘤、10例新鲜正常卵巢组织中SEMA3F的表达水平,并通过亚硫酸氢盐测序法（BSP）检测上皮性卵巢癌中SEMA3F启动子区的甲基化情况,用SPSS 17.0统计软件分析数据。结果免疫组化显示,SEMA3F在不同卵巢上皮肿瘤组织中的表达水平不同,在上皮性卵巢癌组织中表达下降或缺失明显,结合临床资料分析显示,SEMA3F表达与上皮性卵巢癌的临床分期（χ2=27.100,P〈0.001）、组织学分级（χ2=10.673,P=0.005）及有无盆腔外腹膜转移（z=-4.447,P〈0.001）有关,但与患者的年龄（z=-0.670,P=0.503）、组织分类（χ2=3.729,P=0.444）和淋巴结转移（z=-0.584,P=0.559）无关。Kaplan-Meier分析显示,SEMA3F阴性或低表达组患者5年生存率为23.5%（16/68）,明显低于SEMA3F高表达组的52.6%（10/19）,差异有统计学意义,χ2=7.460,P=0.006。RT-PCR结果显示,SEMA3FmRNA相对表达量在正常卵巢组织（1±0.080）、良性卵巢上皮肿瘤（0.927±0.116）和上皮性卵巢癌中（0.436±0.122）依次下降,前两者表达差异无统计学意义,t=0.533,P〉0.05,但正常卵巢与上皮性卵巢癌组织中SEMA3F的表达差异有统计学意义,t=3.820,P〈0.05,且良性卵巢上皮肿瘤与上皮性卵巢癌组织中SEMA3F表达差异亦有统计学意义,t=2.979,P〈0.05。上皮性卵巢癌和正常卵巢组织中SEMA3F启动子区的平均甲基化率分别为23.17%和20.00%,两?     

Morphological and immunohistochemical studies of the estrogen-induced Syrian hamster renal tumor: probable cell of origin

Chronic natural or synthetic estrogen treatment of Syrian golden hamsters leads to the development of malignant renal neoplasms. In the present study, morphological and immunohistochemical studies were performed to further characterize the estrogen-induced hamster renal tumors. The neoplasms were composed of two distinct cell populations: a large-cell component that appeared highly epithelial, and a poorly differentiated small-cell component. Importantly, both cell types had epithelial characteristics, since they contained desmosomes at their cell surfaces. However, the large-cell component possessed additional epithelial features such as microvilli, intracytoplasmic lumens, and cilia. Comparative studies of renal tumors and developing renal tissue from fetal and newborn hamsters revealed remarkable histological similarities. Morphologically, the large tumor cells resembled early metanephric tubules and the small tumor cells were very similar to the blastemal cells of the developing kidney. The earliest tumor foci were found after 4.5 months of treatment. They were consistently found in the kidney interstitium in proximity to large arteries. Immunohistochemical staining for intermediate filaments in developing fetal and newborn kidneys demonstrated cytokeratin in renal tubules, desmin in blastemal cells, and vimentin in stromal cells. Estrogen-induced renal tumor cells uniquely possessed reactivity for all three intermediate filaments, clearly demonstrating their epithelial and mesenchymal characteristics. Based on their morphological resemblance to developing embryonic kidney cells and the presence of both epithelial and mesenchymal intermediate filaments, our findings provide strong evidence that the cell of origin of this malignant tumor is a precursor cell that is committed to an epithelial differentiation pathway.     

Surgical,Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Systematic Review

IntroductionThymic epithelial tumors are rare and are classified as thymoma, thymic carcinoma, and thymic neuroendocrine tumors. The objective of this systematic review was to evaluate the treatment options for patients with thymic epithelial tumors.MethodsThis systematic review was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing surgical, radiotherapy, or systemic treatments against any combination of these treatments in patients with thymic epithelial tumors. Meta-analyses were conducted with clinically homogenous studies.ResultsA total of 106 studies were included, mainly from observational studies. There was an overall survival benefit with postoperative radiotherapy for patients with thymic carcinoma (hazard ratio = 0.65, 95% confidence interval: 0.47–0.89) and for patients with thymoma (hazard ratio = 0.70, 95% confidence interval: 0.59–0.82), especially for those with a high risk for mortality. Patients with thymic carcinoma or thymoma had a response to chemotherapy. Selection bias affected the results for studies that evaluated neoadjuvant chemotherapy or minimally invasive surgical techniques. Furthermore, the overall survival benefit found for adjuvant chemotherapy may have been confounded by the administration of postoperative radiotherapy.ConclusionsFor patients with thymoma or thymic carcinoma, the literature is of low quality and subject to bias. There were overall survival benefits with postoperative radiotherapy. The results of this systematic review were used to inform treatment recommendations in a clinical practice guideline. Future large-scale prospective studies that control for confounders are needed.     

胸腺非典型性类癌的临床病理及免疫组化表型

目的：了解胸腺非典型性类癌的临床病理特征。方法：收集2例胸腺非典型性类癌的临床资料,手术切除组织光镜切片观察,另作10项免疫组织化学标记：CKp,EMA,Ki-67,CD3,CD20,CD5,TdT,NSE,CgA,Syn。结果：2例胸腺非典型性类癌均为男性,纵膈肿瘤,由小园形细胞构成。瘤细胞CKp、EMA、NSE、CgA、Syn阳性,CD3、CD5、CD20、TdT阴性,Ki-67核阳性细胞指数〉20%,肿瘤有显著坏死。结论：非典型性类癌是一种罕见的胸腺肿瘤,诊断靠病理组织学和免疫组织化学标记,手术切除为主要治疗方法。     

Molecular subgroups of small (pT1) breast carcinomas belonging exclusively to the ductal infiltrating variety

BACKGROUND: The use of microarray technology has resulted in a new classification of breast cancer according to gene expression profiles. None of the reports published so far using this new classification has stratified the studied tumors by histology or size. MATERIALS AND METHODS: This study was restricted to the ductal infiltrating variety only, and to pT1 size using the immunohistochemical markers estrogen receptor (ER), progesterone receptor (PR), HER2 and cytokeratin 5/6. ER+ and/or PR+, HER2- tumors were termed "luminal A"; ER+ and/or PR+, HER2+ "luminal B"; triple-negative, CK 5/6+ and/or HER1+ "basal-like"; with an additional category for ER-, PR-, HER2+ tumors termed HER2, and a final group of unclassified ones, negative for all five markers. RESULTS: Out of 346 tumors, 251 (72.5%) were luminal A, 45 (13%) were "triple-negative" ("basal"-like), 20 (5.8%) were luminal B, and 30 (8.7%) were HER2. Luminal A, "triple-negative" ("basal"-like), and HER2-expressing tumors (luminal B + HER2) showed significantly different associations with histological and nuclear grade, mutant p53 expression and Ki67 labelling index. CONCLUSION: Studies of the other, less frequent histological varieties of breast cancer, stratifying by tumor size, are mandatory to disclose which precise gene-expression pattern defines similar subgroups.