BACKGROUND: The distinction between non-invasive and invasive or thymic carcinoma has been severely compromised by lack of objective morphological criteria. A reliable biological marker of tumor aggressiveness is, therefore, mandatory for predicting tumor behavior. MATERIAL AND METHOD: Thirty thymic epithelial tumors, including 7 non-invasive thymoma, 10 invasive thymoma, and 13 thymic carcinoma of the Rosai's classification; and 5 stage I, 7 stage II, 2 stage III, and 3 stage IVa of the Masaoka stage of thymoma were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. RESULT: The thymic epithelial cells showed positive immunostain for bcl-2 in 0 (0%), 3 (30%), 8 (61.5%) of categories in the Rosai's classification respectively and in 0 (0%), 1 (14.3%), 2 (100%), 0 (0%) of stage I, II, III, IVa of the Masaoka stage respectively. Thymic carcinoma, and high stage thymoma had significantly higher proportion of bcl-2 expression than thymoma (p=0.021) and low stage thymoma (p=0.011). However, p53 showed no correlation with the histological subtypes nor with clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoactivity (p=0.007, kappa=0.525). CONCLUSION: These date indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial tumors, but further studies on mutation of p53 protein is necessary because bcl-2 expression appeared to be positively correlated with p53 immunoactivity.
Biomarkers ; Classification ; Epithelial Cells ; Immunohistochemistry ; Thymoma ; Thymus Neoplasms

Carcinoma ; classification ; pathology ; Consensus ; Humans ; Thymoma ; classification ; pathology ; Thymus Neoplasms ; classification ; pathology ; World Health Organization

We retrospectively studied 53 cases of thymic tumors diagnosed after thymectomy to clearfied the pathologic difference of thymic tumor associated with myasthenia gravis and without myasthenia gravis. Among them, there are 23 cases with myasthenia gravis; 19 among 36 thymomas(52.8%), 3 of 4 thymolipoma (75%) and 1 squamous cell carcinoma. Lymphoma and teratoma are not associated with myasthenia gravis. There is no significant difference in the prevalence of myasthenia gravis between types of the old traditional classification of thymoma. But according to the new Muller-Hermelink classification, about two-thirds of myasthenia gravis have the thymoma with cortical cell origin. The prevalence of myasthenia gavis were relatively low in the patients with thymoma of medullary or mixed type. The frequent association of myasthenia gravis was suggesting that the thymolipoma might be a variant of thymoma, cortical type.
Carcinoma, Squamous Cell ; Classification ; Humans ; Lymphoma ; Myasthenia Gravis* ; Prevalence ; Retrospective Studies ; Teratoma ; Thymectomy ; Thymoma ; Thymus Gland* ; Thymus Neoplasms

For the purpose of investigating the pattern of E-cadherin (E-CD) expression in thymomas, 72 cases were immunostained using monoclonal antibody (HECD-1) and microwave-enhanced immunohistochemical method on formalin-fixed, paraffin-embedded tissue sections. The thymomas were classified according to modified Muller-Hermelink classification. The spindle-shaped, medullary type tumor epithelial cells in medullary (3 cases) and composite type (20 cases) thymomas rarely expressed E-CD except in focal areas showing microcystic change observed in 8 cases. Meanwhile, the cohesive epithelioid tumor cells in every case of well-differentiated thymic carcinomas (WDTC) (29 cases) expressed E-CD. The epithelial cells in cortical type (13 cases) expressed stronger E-CD compared with those of organoid type (7 cases). In cases of WDTC admixed with cortical type, we observed increasing expression of E-CD as the tumor epithelium forms cohesive sheets. We could not find any loss of E-CD expression in invasive foci of the 11 cases of high-staged WDTC examined. Since the results of our study show a strong correlation between E-CD expression and epithelioid morphology of the tumor, E-CD seems to play a major role as a morpho-regulatory factor rather than as a suppressor of invasion in organotypic thymomas.
Adolescence ; Adult ; Aged ; Cadherins/immunology ; Cadherins/analysis* ; Female ; Human ; Immunohistochemistry ; Male ; Middle Age ; Neoplasm Staging ; Thymoma/pathology ; Thymoma/classification ; Thymoma/chemistry* ; Thymus Neoplasms/pathology ; Thymus Neoplasms/classification ; Thymus Neoplasms/chemistry*

Carcinoma, Neuroendocrine ; pathology ; Carcinoma, Squamous Cell ; pathology ; Humans ; Neoplasm Staging ; Thymoma ; classification ; pathology ; Thymus Neoplasms ; classification ; pathology ; World Health Organization

BACKGROUND & PURPOSE: Thymic tumors are frequently found in patients with myasthenia gravis(MG); the patients with thymoma seem to be more associated with severe MG. This study was performed to analyse the clinical characteristics of thymic tumor-associated MGs and to compare the patients with invasive and noninvasive thymomas. METHODS: We retrospectively reviewed the medical records of 305 MG subjects(M:F = 112:193, age = 30.4 ? 8.1 years) who had been diagnosed to have MG from January 1986 to June 1996, and analysed the clinical characteristics of MG subjects with thymic tumors. Forty seven patients were confirmed to have thymic tumor by the postoperative histopathologic findings(thymic tumor(TT) group) and 191 were known to have nonneoplastic thymus by chest CT or postoperative histopathologic findings(nonneoplastic thymus(NN) group). RESULTS: The incidence of thymic tumor-associated MG was 25.2%. The male to female ratio for the TT and the NN groups were 1:1 and 1:2, and the mean age of onset were 42.9 ? 11.2 years and 28.3 ? 17.5 years, respectively. When we evaluated the disease severity by Osserman's classification, 85% of the TT group and 51% of NN group were severely affected(Iib, III, IV). The generalization of symptoms occurred in 98% of the TT group and 66% of the NN group. The disease severity and the clinical outcome were not significantly different between the MGs with invasive thymoma, noninvasive thymoma and thymic carcinoma. CONCLUSION: Compared with those of MGs with nonneoplastic thymus, the thymic tumor-associated MGs showed several different clinical phenotypes, as in the followings; they showed no sex predominance, the onset age was older, more common generalization of myasthenic symptoms, and more patients were severely affected. The severity and outcome were not different between the MGs with thymic tumor.
Age of Onset ; Classification ; Female ; Generalization (Psychology) ; Humans ; Incidence ; Male ; Medical Records ; Myasthenia Gravis* ; Phenotype ; Retrospective Studies ; Thymectomy ; Thymoma ; Thymus Gland ; Thymus Neoplasms ; Tomography, X-Ray Computed

OBJECTIVETo study the correlation between amplification of chromosome 1 and histological typing and clinical staging of thymic epithelial tumors according to the WHO classification.

METHODSAmplification of chromosome 1 was detected by interphase fluorescence in-situ hybridization (FISH) in 60 cases of thymic epithelial tumors, including type A thymoma (2 cases), type AB (19 cases), B1 (4 cases), B2 (14 cases), B3 (11 cases), metaplastic thymoma (2 cases), and thymic carcinoma (8 cases) and 11 samples of normal thymus.

RESULTSGain on chromosome 1 was found in 19 cases (31.7%) of thymic epithelial tumors, and none was detected in normal thymic tissues (P < 0.05). The positive rates of gain on chromosome 1 were statistically different among various histological subtypes of thymic epithelial tumors (P < 0.05), in which the highest rate of detection was in thymic carcinoma (6/8), the second, type B3 (6/11), followed by type A (1/2), type AB (4/19), type B2 (2/14) and type B1 (0). The positive rate of gain on chromosome 1 in type B3 had no statistical difference from thymic carcinoma (P > 0.05), but significantly higher than that in other types of thymoma (P < 0.05). In addition, the polysomy rate of chromosome 1 was significantly different among the thymic epithelial tumors at different clinical stages (P = 0.023), and that at stages III and IV was statistically higher than that in stages I and II (P = 0.003) but there was no significant difference between stage I and stage II tumors (P = 0.750).

CONCLUSIONSGain on chromosome 1 is more common in thymic carcinoma and type B3 thymoma than that in other subtypes of thymic epithelial tumors. Thymoma of type B3 may have different genetic features from other subtypes. Detection of gain on chromosome 1 by FISH is helpful in the differential diagnosis and prediction of prognosis in patients with thymic epithelium tumors.

Adult ; Aged ; Carcinoma, Squamous Cell ; genetics ; pathology ; Chromosomes, Human, Pair 1 ; genetics ; Female ; Follow-Up Studies ; Gene Amplification ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Polyploidy ; Prognosis ; Thymoma ; classification ; genetics ; pathology ; Thymus Neoplasms ; classification ; genetics ; pathology

OBJECTIVETo study the prognostic and clinical relevance of histologic subtyping of thymoma according to the World Health Organization (WHO) classification.

METHODSThe clinicopathologic features of 108 patients with thymoma removed surgically were retrospectively reviewed. The histologic diagnosis of the tumors was made on the basis of 2004 WHO classification by two experienced pathologists. The correlation between Masaoka tumor stage, WHO histologic subtype, completeness of resection, presence of myasthenia gravis, other clinical parameters (including age, gender and tumor size) and survival was studied.

RESULTSAccording to WHO classification, there were 7 cases (6.5%) of type A thymoma, 19 cases (17.6%) of type AB thymoma, 23 cases (21.3%) of type B1 thymoma, 19 cases (17.6%) of type B2 thymoma, 27 cases (25.0%) of type B3 thymoma and 13 cases (12.0%) of type C thymoma. According to Masaoka tumor staging, 36 cases (33.3%) were in stage I, 34 cases (31.5%) in stage II, 27 cases (25.0%) in stage III and 11 cases (10.2%) in stage IV(a). The association between histologic subtype and Masaoka tumor stage was statistically significant (P = 0.000). The 5-year survival rates of type A, AB, B1, B2 and B3 thymoma cases were 100%, 100%, 93%, 83% and 43%, respectively; while the 10-year survival rates were 100%, 100%, 81%, 70% and 33%, respectively. The median survival time of type C thymoma was 62.5 months. Type B2 and B3 thymoma cases had an intermediate prognostic ranking in comparison with type C thymoma and other groups (P = 0.000). The 5-year survival rates of tumors in stage I, II and III were 100%, 77% and 54%, respectively; while the 10-year survival rates were 100%, 70% and 27%, respectively. The median survival time of patients in stage IV(a) was 14.0 months. Masaoka tumor stage was highly significant in predicting survival of patients (P = 0.000). On multivariate analysis, Masaoka tumor stage was an independent predictive factor for survival (P = 0.027). On the other hand, the WHO subtype (type A to B1 versus type B2 to B3 versus type C) and completeness of resection could predict the tumor-related survival.

CONCLUSIONSThe Masaoka tumor stage is the single most important prognostic factor of thymoma. The WHO histologic subtype and completeness of resection affect mainly the post-operative survival. The classification of thymoma may also reflect the clinical behavior of the tumor. Type A, AB and B1 thymomas belong to the low-risk group, while type B2 and B3 thymomas have an intermediate prognostic ranking. Type C thymoma carries the worst prognosis.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Myasthenia Gravis ; etiology ; Prognosis ; Survival Analysis ; Thymoma ; classification ; complications ; diagnosis ; pathology ; Thymus Neoplasms ; classification ; complications ; diagnosis ; pathology ; World Health Organization

OBJECTIVETo study the relationship between activation of pro-MMP-2 and expression of matrix metalloproteinases (MMP)-2, MT1-MMP and tissue inhibitor of metalloproteinases (TIMP)-2 mRNA in thymoma and thymic carcinoma; and to study the molecular mechanism of invasion and metastasis of thymic epithelial tumors.

METHODSFresh tissue specimens of thymoma, thymic carcinoma and normal thymus were included. The mRNA expression of MMP-2, MT1-MMP and TIMP-2 were analyzed by real-time reverse transcription polymerase chain reaction. The pro-MMP-2 activation ratio and its localization were determined by gelatin zymography and film in-situ gelatin-Zymography, respectively. Correlation of mRNA expression of MMP-2, MT1-MMP and TIMP-2 was investigated in tumors with different histological subtypes and clinical stages.

RESULTSThere were no significant differences in the expressions of MMP-2, MT1-MMP and TIMP-2 mRNA between I and II stage or III and IV stage thymomas (P > 0.05). However, significant differences of the expressions were observed between three tumor groups: I-II stage, III-IV stage and thymic carcinomas (P < 0.005), and between three histological subtypes: AB-B1 (lymphocyte-rich and mixed types), B2-B3 (cortical and predominantly polygonal cells types) and thymic carcinomas (P < 0.05). Expression levels of MT1-MMP and TIMP-2 mRNA were correlated with pro-MMP-2 activation ratio (Spearman rank correlation: r = 0.7235, r = 0.7647, P < 0.005). The expression of MMP-9 did not show significant differences between thymomas and thymic carcinomas.

CONCLUSIONSMMP-2, MT1-MMP and TIMP-2 mRNA expression levels are correlated with the histologic subtypes and clinical stages of thymoma. The mRNA expressions of MT1-MMP and TIMP-2 are correlated with the activation ratio of pro-MMP-2. It is speculated that upregulation of MT1-MMP gene expression may induce an activation of pro-MMP-2 through TIMP-2.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; enzymology ; metabolism ; pathology ; Enzyme Activation ; Female ; Humans ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinases ; biosynthesis ; genetics ; Matrix Metalloproteinases, Membrane-Associated ; Middle Aged ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; genetics ; Thymoma ; classification ; enzymology ; metabolism ; pathology ; Thymus Gland ; enzymology ; metabolism ; Thymus Neoplasms ; classification ; enzymology ; metabolism ; pathology ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics

OBJECTIVETo study the clinicopathologic characteristics of thymic epithelial tumors and to evaluate the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system.

METHODSThe morphology and immunophenotype of 52 cases of thymic epithelial tumor were reviewed. The tumors were classified according to the new WHO classification system and the clinical data were analyzed.

RESULTSOf the 52 cases studied, 45 were thymomas and 7 were thymic carcinomas. Amongst the 45 cases of thymoma, 6 (13.4%) were type A, 15 (33.3%) were type AB, 4 (8.9%) were type B1, 9 (20.0%) were type B2, 9 (20.0%) were type B3 and 2 (4.4%) were metaplastic thymoma. Amongst the 7 cases of thymic carcinoma, 6 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The commonest presentations were cough and chest pain. Some cases were incidentally discovered by routine physical examination. Thirteen cases (25.0%) of thymoma were associated with myasthenia gravis. CT scan showed that 49 cases (94.2%) were located in the anterior mediastinum. All cases of type A, AB and B1 thymoma and most cases of B2 thymoma appeared as well-defined homogeneous mass, whereas a few cases of type B2 thymoma and most cases of type B3 thymoma and thymic carcinoma were poorly demarcated and heterogeneous. According to Masaoka staging system, 20 cases (41.7%) belonged to stage I, 15 cases (31.3%) stage II, 11 cases (22.9%) stage III and 2 cases (4.1%) stage IV. The histologic subtypes of thymic epithelial tumors significantly correlated with the clinical stages (chi(2) = 32.5, P < 0.01).

CONCLUSIONSThe 2004 revision of WHO histologic classification system for thymic epithelial tumors shows a high degree of reproducibility. Correlation with the radiologic, clinical and prognostic parameters is helpful in determining the management strategy for individual patients.

Adult ; Aged ; Antibodies, Monoclonal ; analysis ; Antigens, CD20 ; metabolism ; CD5 Antigens ; metabolism ; Carcinoma, Neuroendocrine ; classification ; diagnostic imaging ; metabolism ; pathology ; Carcinoma, Squamous Cell ; classification ; diagnostic imaging ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Keratins ; immunology ; Male ; Middle Aged ; Myasthenia Gravis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Thymoma ; classification ; diagnostic imaging ; metabolism ; pathology ; Thymus Neoplasms ; classification ; diagnostic imaging ; metabolism ; pathology ; Tomography, X-Ray Computed