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*

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

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

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

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

Cutaneous nocardiosis, which usually manifests in the form of pustules, abscesses, or subcutaneous nodules, is occasionally found in immunocompromised patients. A 59-yr-old Korean man with myasthenia gravis and thymoma developed nodular skin lesions on his trunk. Histopathologically, abscess formation with a dense infiltrate of neutrophils and many cytophagic histiocytes were observed. Numerous filamentous organisms, which turned out to be Nocardia asteroides by culture, were also found. After sulfamethoxazole-trimethoprim therapy, all of the skin lesions rapidly decreased in size, with a marked diminution of the number of cytophagic histiocytes, and cleared up within four months. On reporting a case of cutaneous nocardiosis showing unusual histopathologic findings, we considered that reactive conditions should be included in the differential diagnosis of the cutaneous cytophagocytosis, and that nocardiosis could be one of the diseases showing reactive cytophagocytosis.
Anti-Bacterial Agents/therapeutic use ; Histiocytes/*immunology ; Humans ; Male ; Middle Aged ; Myasthenia Gravis/complications ; Neutrophils/*immunology ; Nocardia Infections/drug therapy/*immunology/microbiology/pathology ; Nocardia asteroides/drug effects/*immunology/isolation & purification ; Phagocytosis/*immunology ; Skin Diseases, Bacterial/drug therapy/*immunology/microbiology/pathology ; Thymoma/complications ; Thymus Neoplasms/complications ; Treatment Outcome ; Trimethoprim-Sulfamethoxazole Combination/therapeutic use

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