OBJECTIVETo study the expression of CD20 in thymomas and its clinical significance.

METHODSOne hundred and seventy-nine cases of thymoma were enrolled into the study. The histologic diagnosis was reviewed by two experienced pathologists on the basis of the 2004 WHO classification. One hundred and two cases were selected for immunohistochemical study for CD20, pancytokeratin, TdT, CD3, CD43, CD99 and S-100 protein. The cases were further categorized into two groups, according to the association with clinical evidence of myasthenia gravis. The immunostaining pattern was then statistically analyzed.

RESULTSAmongst the 102 cases studied, 7 cases belonged to type A thymoma, 32 cases type AB thymoma, 17 cases type B1 thymoma, 15 cases type B2 thymoma, 17 cases type B3 thymoma and 14 cases thymic carcinoma. The expression rates of CD20 in neoplastic epithelial cells of type A, type AB, type B1, type B2 and type B3 thymomas and thymic carcinomas were 3/7, 84.4% (27/32), 1/17, 2/15, 0/17, 0/14, respectively. The proportions of CD20-positive lymphocytes in the background were 3/7, 18.8% (6/32), 14/17, 11/15, 11/17, 6/14, respectively. The proportion of CD20-positive intra-tumoral B lymphocytes in the group of thymomas with myasthenia gravis was 67.5% (22/40), in contrast to 35.5% (22/62) in those without myasthenia gravis.

CONCLUSIONSThe neoplastic epithelial cells in cases of type A and type AB thymoma, as well as few cases of type B1 and B2 thymoma, express CD20. The immunostain highlights the presence of oval, stellate or spindly cells. Thymomas associated with myasthenia gravis contain a significant population of CD20-positive intra-tumoral B lymphocytes. Type AB thymomas may be originated from different populations of cells, rather than a simple admixture of type A and B thymoma cells.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; B-Lymphocytes ; immunology ; pathology ; Child ; Epithelial Cells ; immunology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; complications ; immunology ; pathology ; Thymoma ; classification ; complications ; immunology ; pathology ; Thymus Neoplasms ; classification ; complications ; immunology ; pathology ; Young Adult

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

Adult ; Antibodies, Monoclonal ; analysis ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Follow-Up Studies ; Humans ; Keratins ; immunology ; Male ; Middle Aged ; Prognosis ; Thymoma ; metabolism ; pathology ; surgery ; Thymus Neoplasms ; metabolism ; pathology ; surgery

Germ-line mutations in BRCA2 predispose to early-onset cancer. Homozygous mutant mouse, which has Brca2 truncated in exon 11 exhibit paradoxic occurrence of growth retardation and development of thymic lymphomas. However, due to its large embryonic lethality, cohort studies on the thymic lymphomas were not feasible. With the aid of Cre-loxP system, we demonstrate here that thymus-specific disruption of Brca2 allele without crossing it to p53-mutant background leads to the development of thymic lymphomas. Varying from 16 weeks to 66 weeks after birth, 25% of mice disrupted of Brca2 in the thymus died of thymic lymphomas, whereas previous report did not observe lymphomagenesis using similar Cre-loxP system. Future analysis of thymic lymphomas from these mice presented here will provide information on the cooperative mutations that are required for the BRCA2-associated pathogenesis of cancer.
Animals ; BRCA2 Protein/deficiency/*genetics ; CD4-CD8 Ratio ; Cell Separation ; Flow Cytometry ; Integrases/*genetics/immunology ; Lymphoma/*genetics/immunology/metabolism/pathology ; Mice ; Mice, Knockout ; Organ Specificity ; *Sequence Deletion ; T-Lymphocytes/enzymology/*immunology ; Thymus Gland/immunology/metabolism/pathology ; Thymus Neoplasms/*genetics/immunology/metabolism/pathology ; Tumor Suppressor Protein p53/deficiency/genetics/immunology

Good's syndrome is extremely rare. This adult-onset condition is characterized by a thymoma with immunodeficiency, low B- and T-cell counts, and hypo-gammaglobulinemia. The initial clinical presentation is either a mass-lesion thymoma or a recurrent infection. Patients with Good's syndrome are very susceptible to infections; common respiratory and opportunistic infections can be life-threatening. There are no reports of granulomatous lung disease in patients with Good's syndrome, although it has been observed in patients with common variable immunodeficiency, of which Good's syndrome is a subset. We describe a 53-year-old male thymoma patient who presented with respiratory symptoms caused by granulomatous lung disease and an opportunistic infection. He died of uncontrolled fungal infection despite repeated intravenous immunoglobulin and supportive care. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with severe recurrent infections, especially opportunistic infections.
Fatal Outcome ; Granuloma, Respiratory Tract/diagnosis/*etiology/therapy ; Humans ; Immunologic Deficiency Syndromes/*complications/immunology/pathology ; Lung Diseases/diagnosis/*etiology/therapy ; Male ; Middle Aged ; Thymoma/*complications/immunology/pathology ; Thymus Neoplasms/*complications/immunology/pathology

OBJECTIVETo explore the clinical significance of serum anti-ryanodine receptor (RyR) antibody in the diagnosis of myasthenia gravis (MG).

METHODSThe crude sarcoplasmic reticulum was prepared from rabbit skeletal muscle, and then purified by differential centrifugation to produce the antigen. The serum anti-RyR antibody levels in 74 patients with MG (including 21 patients with comorbidic thymomas) were determined with ELISA.

RESULTSWestern blot demonstrated the presence of RyR in purified crude sarcoplasmic reticulum. The positive rate of anti-RyR antibody was significantly higher in MG patients who had comorbidic thymoma compared with those who had no such comorbidity (P < 0.01). Also, the positive rate was closely correlated with the severity of MG.

CONCLUSIONSerum anti-RyR antibody test is helpful in the diagnosis of MG associated with thymoma and can be used to judge the outcome of MG.

Autoantibodies ; blood ; Humans ; Myasthenia Gravis ; blood ; complications ; immunology ; Ryanodine Receptor Calcium Release Channel ; immunology ; Thymoma ; complications ; Thymus Neoplasms ; complications

OBJECTIVETo investigate the clinical significance of the serum anti-titin, anti-ryanodine receptor (RyR) antibody level and thymus CT scan in the diagnosis of myasthenia gravis with thymoma.

METHODSTotally 32 patients with myasthenia gravis who had received thymectomy were included in the study. Abnormalities were shown under CT scan of thymus in all these patients. The relationships were studied among the pathological diagnosis, CT findings, and serum level of thymoma associated antibodies: anti-titin and anti-RyR antibodies.

RESULTSThe pathological diagnosis of thymoma was made in 21 patients and thymus hyperplasia in 11 patients after operation. The sensitivity of CT scan in the diagnosis of thymomas was 90.5%, the specificity of serum thymoma associated antibodies in the diagnosis of thymoma was 100%.

CONCLUSIONThe thymoma-associated antibodies test is helpful in the differential diagnosis of thymomas and thymus hyperplasia; when combined with CT scan, it may achieve high sensitivity in the diagnosis of the thymoma.

Adult ; Antibodies, Neoplasm ; blood ; immunology ; Autoantibodies ; blood ; Biomarkers, Tumor ; blood ; Female ; Humans ; Male ; Myasthenia Gravis ; complications ; diagnostic imaging ; immunology ; Ryanodine Receptor Calcium Release Channel ; immunology ; Thymoma ; complications ; diagnostic imaging ; immunology ; Thymus Hyperplasia ; diagnostic imaging ; immunology ; Thymus Neoplasms ; complications ; diagnostic imaging ; immunology ; Tomography, X-Ray Computed

OBJECTIVETo study the genetic pathogenesis of myasthenia gravis (MG) caused by cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphisms and regulation function of transcription factor.

METHODSELISA assay was used to determine the expression level of serum sCTLA-4 in MG. Four single nucleotide polymorphisms (SNPs) of CTLA-4 at exon 1 +49, promoter -318, -1661, -1772 were analyzed by restriction fragment length polymorphism (RFLP). Transcription factor nuclear factor 1(NF-1) and c/EBPbeta binding site were confirmed by chromatin immunoprecipitation(CHIP) assay.

RESULTSIt was found that the frequencies of the GG+49 genotype and G+49 allele are higher in MG patients with thymoma than those in patients of thymic hyperplasia and normal thymus subgroups. T/C-318 is not correlated with MG. The frequency of CT-1772 genotype is significantly higher in MG patients, especially in MG patients with thymoma, when compared with that in healthy controls. Meanwhile, the frequency of the G-1661 allele and GG-1661 genotype is lower in MG patients. Linkage disequilibrium (LD) between each SNPs in promoter -1772, -1661, -318 and coding sequence 1 (CDS 1) +49 is apparent. sCTLA-4 levels in patients' sera are correlated with the haplotype and genotype. T/C-1772 and A/G-1661 SNPs change the sequence of transcription factor NF-1 and c/EBPbeta binding sites. DNA variants lose site-specific binding activity of transcription factor regulated by lectin ConA and PHA.

CONCLUSIONThere are strong positive linkages among four SNPs. C/T-1772 and A/G-1661 polymorphisms can result in inefficient transcription of CTLA-4 gene. T>C-1772 mutation also affects gene splicing. These SNPs may constitute a factor of susceptibility to disease.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; Antigens, Differentiation ; blood ; genetics ; CCAAT-Enhancer-Binding Protein-beta ; genetics ; CCAAT-Enhancer-Binding Proteins ; genetics ; CTLA-4 Antigen ; Exons ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; genetics ; immunology ; NFI Transcription Factors ; Point Mutation ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Thymoma ; genetics ; Thymus Hyperplasia ; genetics ; Thymus Neoplasms ; genetics ; Transcription Factors ; genetics

For a long time, thymic function could not be monitored, as a consequence of the absence of adequate technology to detect recent thymic emigrants from naive T cells. T cell differentiation in the thymus is characterized by T cell receptor (TCR) rearrangement. During the rearrangement of TCRalpha gene segments, the deltaRec and psiJalpha rearrange to each other to delete the TCRdelta gene and form an extrachromosomal DNA circles, referred to as signal joint T cell receptor excision DNA circles (sjTRECs) or TRECs. TRECs are assumed to have a high stability, they can not multiply and consequently are diluted during T cell proliferation. It was recently suggested that quantitative detection of TRECs would allow for direct measurement of thymic output. In this review TRECs quantification is a powerful method to evaluate the thymic output function in both health and disease, including hematopoietic stem cell transplantation, hematopoietic malignancies, HIV infection and autoimmune disease, and so on is described.
Animals ; Cell Differentiation ; Cell Movement ; Gene Rearrangement, T-Lymphocyte ; HIV Infections ; immunology ; Humans ; Immunity ; Neoplasms ; immunology ; T-Lymphocytes ; physiology ; Thymus Gland ; physiology

Primary thymic marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT)-type is a very rare disease with distinct clinicopathologic features. I herein report a rare case of primary thymic MZBL of MALT-type arising in the thymus in a patient with Sjogren's syndrome and rheumatoid arthritis. A mediastinal mass was detected by computerized tomography in a 43-yr-old Korean woman with a history of Sjogren's syndrome and rheumatoid arthritis and the thymus was resected through median sternotomy. The solid and nodular tumor (7x6x3cm) was confined in the thymus. Histologically, the lymphoid infiltrate comprised monotonous centrocyte-like cells with monocytoid cells, small lymphocytes, and plasma cells. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating the Hassall's corpuscles. Immunohistochemically, the tumor cells were positive for CD20, CD79a, and bcl-2 and negative for CD3, CD5, CD10, CD23, and bcl-6. IgA and kappa light chain restriction were also found in plasma cells in the tumor. Sjogren's syndrome and rheumatoid arthritis are known to be associated with MALT lymphoma and were considered to play an important role in the development of malignant lymphoma in this patient.
Adult ; Arthritis, Rheumatoid/*complications/immunology ; B-Lymphocytes/metabolism ; Female ; Human ; Lymphoma, Mucosa-Associated Lymphoid Tissue/diagnosis/*etiology/immunology ; Sjogren's Syndrome/*complications/immunology ; Thymus Neoplasms/immunology/*pathology ; Tumor Markers, Biological