Ocular myasthenia gravis secondary to thymoma

Thymoma is a neoplasm that originates from the epithelial cells of the thymus gland. Approximately 15% of patients with thymoma will present with symptoms of myasthenia gravis (MG),an autoimmune disorder involving the neuromuscular junction. Approximately 50% of patients with symptoms of myasthenia gravis will have thymoma. This paper presents a case report of thymoma and discusses the ocular and systemic manifestations of this uncommon neoplasm. Special emphasis is placed on the association between thymoma and myasthenia gravis.     

Epithelial cytologic atypia in a fine needle aspirate of an invasive thymoma. A case report.

Fine needle aspiration of a superior-anterior mediastinal mass in a 35-year-old man revealed sheets and clusters of epithelial cells intermingled with a few lymphocytes, characteristic of a thymoma. The presence of atypical cytologic features, such as nuclear pleomorphism, large and vesicular nuclei, prominent nucleoli and frequent mitotic figures, in the epithelial cells caused diagnostic confusion with a thymic carcinoma. However, the subsequent clinical and histologic findings were consistent with an invasive epithelial thymoma. The cytologic features in the present case showed that thymoma with intermediate cytology between that of an ordinary thymoma and thymic carcinoma may be encountered in fine needle aspirates of mediastinal tumors. The cytologic differentiation from a carcinoma may be difficult when the degree of epithelial atypia is high. Histologic confirmation is necessary for a definitive diagnosis.     

Tobacco smoking and alcohol consumption as risk factors for thymoma – A European case-control study

PurposeHardly anything is known about the aetiology of thymoma. This paper presents data regarding tobacco smoking and alcohol consumption in relation to thymoma from the first case-control study performed on this rare tumour.MethodsA European multi-centre case-control study including incident cases aged 35–69 years with thymoma between 1995 and 1997, was conducted in seven countries. A set of controls, used in seven parallel case-control studies by the same research group was used, including population-based controls from five countries and hospital controls with colon cancer from two countries. Altogether 103 cases, accepted by a reference pathologist, 712 colon cancer controls, and 2071 population controls were interviewed.ResultsTobacco smoking was moderately related with thymoma (OR 1.4, 95% CI 0.9–2.2), and a tendency to dose-response was shown (p = 0.04), with an increased risk for heavy smokers defined as ≥41 pack-years (OR 2.1, 95% CI 1.1–3.9). A high consumption of spirits defined as ≥25 g of alcohol per day was associated with an increased risk of thymoma (OR 2.4, 95% CI 1.1–5.4), whereas no association was found with beer or wine.ConclusionsTobacco smoking and a high intake of spirits were indicated as risk factors for thymoma.     

Thymoma and thymoma-like tumors of the anterior mediastinum--therapeutic problems in observed patients

In the last years, 11 patients with tumors of anterior mediastinum were treated at the Oncologic Centre in Lód?. Lymphocytic-epithelial thymoma was diagnosed in 6 patients whereas thymoma was suspected in 5 patients. Therapy was a problem mainly in these 5 patients, especially if lymphoma was considered in the differential diagnosis. The authors suggest that therapy should start with cytostatic agents in all patients with mediastinal tumors and morphology which not justifies thymoma diagnosis. Radiotherapy may follow in these cases in which 1-2 chemotherapy cycles failed.     

Establishment of functional epithelial cell lines from a rat thymoma and rat thymus

Summary Seven clonal epithelial cell lines from a thymoma of an (ACI/NMs×BUF/Mna)F1 rat and seven clonal epithelial cell lines from an ACI/NMs rat thymus were established in a medium containing 1 μM dexamethasome (DM) and were characterized cytologically. Long-term treatment of DM stabilized the epithelial nature of these epithelial cells irreversibly. The established cell lines showed a polygonal shape, were positively stained with antikeratin antiserum and had tonofilaments and desmosomes. Species of their keratin paptides were the same as those of normal thymic epithelial cells in primary cultures. The cell lines were positively stained with Th-4 monoclonal antibody which preferentially stains the medullary epithelial cells of the thymus, but not with Th-3 which preferentially stains the subcapsular and cortical epithelial cells of the thymus. The cells from the rat thymoma were much large than those from the normal thymus, as reflected in their primary cultures. No transformed phenotypes, such as high growth rate, high saturation density anchorage independency, low serum dependency and so on, were found on the cell lines from the thymoma as in the cell lines from the normal thymus by in vitro assays. DNA synthesis of the thymic lymphocytes was stimulated by culturing with a line of rat thymoma with no lectins. Thymic lymphocytes strongly bound on the cell lines from the thymoma and changed the shape of the cells. These cell lines may be useful to investigate the mechanism of thymomegenesis and the interactions between epithelial cells and thymocytes in the rat thymoma.     

Possible relationship between poly(ADP-ribose)synthetase and formation of antibody against acetylcholine receptors in patients with myasthenia gravis

We examined the relationship of the serum levels of antibody against acetylcholine receptors to the serum levels of 13 enzymes, including various hydrolytic enzymes, poly(ADP-ribose)synthetase (Poly(ADP-ribose)Syn), and sialyltransferase (NANA-trans), in patients with myasthenia gravis. The patients were divided into two groups, depending on the presence or absence of thymoma. In spite of the absence of significant difference in the absolute levels of individual enzymatic activities between the two groups, the network relationships of such enzymes were quite different between the two groups. Of the 13 enzymes examined, only Poly(ADP-ribose)Syn showed a weak but significant correlation with the level of the antibody in the patients without thymoma. A multivariate study more clearly suggested the relationship between the antibody formation and Poly(ADP-ribose)Syn in the patients without thymoma. Such observations were not found in the patients with thymoma.     

Increased expression of c-myc is associated with thymoma in rats infected with murine leukemia virus A8

Infection of rats with Friend murine leukemia virus (Fr-MLV) clone A8 causes thymoma in all the animals within 7 weeks. The rapid induction of thymoma is associated with a unique enhancer structure in the U3 region of the A8-LTR. Our Southern blot analyses showed that the thymomas were oligo clonal. The A8-induced thymomas showed 3-to 11-fold overexpression of c-myc mRNA. These results suggest that provirus insertion into particular positions of the host genome is correlated with tumorigenesis after A8 infection and that up-regulation of c-myc plays an important role in the induction of thymoma.     

Multiomics data reveals the influences of myasthenia gravis on thymoma and its precision treatment

Thymoma is a rare characterized by a unique association with autoimmune diseases, especially myasthenia gravis (MG). However, little is known about the molecular characteristics of MG‐associated thymoma individuals. We aim to examine the influences of MG on thymoma by analyzing multiomics data. A total of 105 samples with thymoma was analyzed from TCGA and these samples were divided into subgroups with MG (MGT) or without MG (MGF) according to clinical information. We then characterized the differential gene expression, pathway activity, somatic mutation frequency, and likelihood of responding to chemotherapies and immunotherapies of the two identified subgroups. MGT subgroup was characterized by elevated inflammatory responses and metabolically related pathways, whereas the MGF subgroup was predicted to be more sensitive to chemotherapy and presented with mesenchymal characteristics. More copy number amplifications and deletions were observed in MGT, whereas GTF2I mutations occur at significantly higher frequencies in MGF. Two molecular subtypes were further identified within MGF samples by unsupervised clustering where one subtype was enriched in TGF‐β and WNT pathways with higher sensitivity to relevant targeted drugs but hardly respond to immunotherapy. For another subtype, a higher recurrence rate of thymoma and more likelihood of responding to immunotherapy were observed. Our findings presented a comprehensive molecular characterization of thymoma patients given the status of MG, and provided potential strategies to help individualized management and treatment.     

Redox regulation of cell proliferation by pyrrolidine dithiocarbamate in murine thymoma cells transplanted in vivo.

Pyrrolidine dithiocarbamate (PDTC) is a synthetic compound largely used in cell biological studies and known to exert either antioxidant or pro-oxidant effects. Recently, its antitumoral activity has been proposed on the basis of its antioxidant and proapoptotic effects. In the present study, we evaluated the effect of increasing i.p. doses of PDTC on the growth of a strain of highly malignant thymoma cells inoculated in the peritoneum of inbred Balb/c mice. PDTC treatment increased the number of thymoma cells in a dose-dependent manner, enhancing the percentage of proliferating tumor cells. PDTC exerted regulatory effects on cell cycle distribution, decreasing the expression of cell cycle inhibitors. Alterations in the production of intracellular reactive oxygen species, levels of oxidized glutathione, and intracellular levels of the redox-active metals iron and copper were also observed. The above results represent the first evidence that PDTC may induce in vivo cell proliferation in a murine thymoma cell model. In addition, we suggest that the ability of PDTC to bind and transport metals inside the cell and its pro-oxidant property may be factors underlying its effects on thymoma cell proliferation and cell cycle distribution.     

Diagnosis of cervical thymoma by fine needle aspiration biopsy with flow cytometry. A case report

BACKGROUND: Cervical thymoma is a rare entity. To our knowledge, this is the 20th reported case of cervical thymoma and the fourth case of fine needle aspiration biopsy (FNAB) of this entity. To our knowledge, this is the only case in which cervical thymoma was a diagnostic consideration at the time of the FNAB diagnosis. The diagnosis was rendered because, unlike in previous cases, flow cytometric immunophenotyping was performed. CASE: A 46-year-old, white female presented with what was clinically thought to be a left thyroid nodule. The patient underwent FNAB at an outside institution, and the diagnosis of "possible mixed lymphoma" was made by morphology alone. The patient was referred to our institution for repeat FNAB. Based upon the cytologic findings (cells with lymphoid morphology), flow cytometry was performed, and a diagnosis of cervical thymoma (versus ectopic thymic tissue) was based upon flow cytometry findings combined with morphology. CONCLUSION: When FNAB of a cervical mass, particularly one clinically thought to be a thyroid nodule, shows lymphoid cells without thyroid follicular cells, immunophenotyping may be extremely helpful in arriving at the correct diagnosis.     

直径大于3厘米的周围型肺癌血流动力学的多排螺旋CT动态增强扫描研究

目的:研究直径3厘米以上周围型肺癌血流动力学的螺旋CT(电子计算机断层扫描,Computed Tomography)动态增强扫描的特点。方法:选取我院收治的肿瘤直径3 cm的周围型肺癌患者55例,肺部腺瘤(良性)患者10例,肺部炎性结节患者26例。分别进行螺旋CT动态增强扫描,记录其CT值、强化峰值(Peak enhancement,PH),绘制动态增强时间-密度曲线,计算并比较曲线最大增强线性斜率(steepes slope,SS)以及血流灌注量(blood perfusion,BP)。结果:肺部炎性结节患者的密度曲线在120 s达到最大值;肺癌患者的密度曲线至65 s达到高峰;胸腺瘤患者的密度曲线变化不明显。肺癌组PH平均值大于胸腺瘤组,差异有统计学意义(P0.05);胸腺瘤组PH平均值小于肺部炎性结节组,差异有统计学意义(P0.05);肺癌组SS和BP大于胸腺瘤组,差异有统计学意义(P0.05);胸腺瘤组SS和BP小于肺部炎性结节组,差异有统计学意义(P0.05)。结论:螺旋CT动态增强扫描能够反映直径3厘米以上周围型肺癌的血流动力学特点从而有助于在肺癌的诊断和鉴别诊断。     

Cytopathology of thymoma

From 1967 to 1981, 37 cases were diagnosed as thymoma by transthoracic fine needle aspiration biopsy. All were verified histologically, with no false-positive results. The various cytomorphologic patterns of thymoma are presented. All aspirates from the thymomas were reviewed and found to be composed of epithelial elements, with an admixture of lymphocytes in various proportions. There were 13 cases of lymphocytic predominance, 11 of epithelial-cell predominance, 4 of spindle-cell predominance, and 9 of mixed cell types. In the cytologic preparations the epithelial elements from different tumors exhibited different cytologic appearances and were tentatively subclassified into five types: small, intermediate, large, large pleomorphic and spindle shaped. The cytologic features of thymoma observed in aspiration biopsies are sufficiently distinctive from those of other anterior mediastinal tumors to be diagnostic. It appears feasible to investigate an anterior mediastinal mass with percutaneous fine needle aspiration for the purpose of establishing the diagnosis of thymoma prior to median sternotomy or thoracotomy.     

The methylation status of FBXW7 beta-form correlates with histological subtype in human thymoma

FBXW7 is reported to be a tumor suppressor gene, and the functional inactivation of FBXW7 has been reported in various human tumors. In this study, we investigated the FBXW7 gene in human thymoma; although no mutations were evident, a significantly high frequency of methylation in the FBXW7 β-form promoter was observed in types B1 or higher (P = 0.014). We propose a novel mechanism for the pathogenesis of thymoma by FBXW7 β-form and hypothesize that expressional suppression plays an important role in the malignant potential of thymoma.     

Recent thymic emigrants as the bridge between thymoma and autoimmune diseases

Recent thymic emigrants (RTEs) are naïve T cells that egress the thymus following intrathymic development. This continuous process, including self-renewal, is crucial to establish and maintain human immune function. Several biomarkers can identify RTEs, but none of them is specific. Additional methods to detect and study RTEs phenotypically and functionally revealed alterations in RTEs in various adverse health conditions, including autoimmune diseases, systemic disorders and thymic abnormalities such as thymoma. Often associated with autoimmune disease, thymoma is the only tumor that can generate RTEs. However, a causal relationship between RTEs and autoimmune disease remains uncertain. Here, we review current knowledge about the connections between thymoma, RTEs and autoimmune diseases to provide new perspectives for therapeutic strategies.     

Expression ofras p21 Protein by Thymoma

Histopathological examination of thymomas often fails to predict their malignant potential because the morphology of invasive or metastatic thymomas does not differ significantly from that of benign, encapsulated thymomas. In order to find a marker of aggressiveness in thymomas, 21 cases (9 non-invasive, 8 invasive and 4 metastatic thymomas) were examined for expression of the ras oncogene product p21 by immunohistochemistry and immunoblot analysis. Immunohistochemical study, using a serially diluted monoclonal antibody, NCC-RAS-001, demonstrated that neoplastic thymoma cells generally contained more p21 than normal thymic epithelial cells. Immunoblot analysis using another monoclonal antibody (NCC-RAS-004) also confirmed the increased concentration of p21 in all but one of the thymomas by comparison with normal thymic tissue. One metastatic thymoma did not have a band of p21 recognized by NCC-RAS-004 and was believed to have a deletion of the epitope recognized by this antibody. In addition, another metastatic thymoma showed abnormal electrophoretic mobility of p21. The increased amount of p21 in thymomas suggests that this protein has a role in the oncogenesis or progression of thymoma. The high incidence of a p21 molecular abnormality in metastatic thymomas indicates that the abnormality of this protein could be used as a possible marker of aggressive behavior.     

Cardiac tamponade as a presentation of malignant thymoma

Morphologic, cytochemical and immunocytochemical studies of pericardial fluid from a 30-year-old man presenting with cardiac tamponade are described. Based on the results of the immunocytochemical studies and the histologic examination of excised pericardium, a diagnosis of malignant thymoma was made. This is the first documented case in which malignant cells were found in the pericardial effusion in a patient with invasive thymoma. The significance of using a multidisciplinary approach to the study of body fluids is discussed.     

Octreotide in the treatment of malignant thymoma – Case report

Thymomas are the most common mediastinal tumors. Systemic therapy for patients with unresectable or recurrent thymomas is a challenging field in the current oncology research. There is some evidence that somatostatin analogs combined with corticosteroids may have a role in the treatment of advanced malignant thymoma; however, the role of these agents have not been fully evaluated.Case reportA 39-year-old man with metastatic thymoma was administered long-acting depot injection form of octreotide. Octreotide scan before the treatment initiation revealed low uptake. CT control after three months of the treatment revealed marked regression of pleural metastases, while the primary tumor mass remained stable. The treatment response was lasting for 9 months.ConclusionWe describe an interesting case of marked clinical and radiological response of advanced malignant thymoma to the treatment with octreotide in a heavily pre-treated patient, even though octreotide scan revealed low uptake.     

Lymphocytes in thymomas are tolerant to self-MHC.

Neoplastic epithelial cells of thymoma apparently retain the function of the cortical epithelial cells of normal thymus because a large number of nonneoplastic T cells in thymomas are often CD4+8+. However, the lack of medullary structure suggests that thymomas may lack some of the function of the normal thymus, especially the function of the medullary interdigitating cells to induce tolerance to self-antigens on T cells. Thymoma is often associated with autoimmune diseases, most frequently, myasthenia gravis. This suggests that the microenvironment of a thymoma may not be able to induce T cell tolerance to self-antigens. We addressed this question by testing the lymphocytes in thymomas for proliferative responses to mitogens and allogeneic or autologous stimulator cells. The lymphocytes in thymomas proliferated consistently in response to PHA and to allogeneic cells even when the response to OKT3 was undetectable. However, neither the thymoma lymphocytes nor the peripheral blood lymphocytes in these patients proliferated in response to autologous cells.     

Ectopic hamartomatous thymoma. Report of a case with fine needle aspiration biopsy findings

BACKGROUND: Ectopic hamartomatous thymoma is a rare, benign tumor occurring exclusively in the supraclavicular and suprasternal regions. To the best of our knowledge, there are no English-language reports on its cytologic findings. CASE: A fine needle aspiration specimen from a mass in the suprasternal region in a 63-year-old male revealed epithelial cell nests, spindle cells, a cluster of mature adipocytes and a small number of lymphocytes. CONCLUSION: Although ectopic hamartomatous thymoma is very rare, fine needle aspiration cytology may contribute to the correct diagnosis in conjunction with the characteristic clinical findings.