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Pericardial involvement by thymomas. Entirely intrapericardial thymoma and a pericardial metastasis of thymoma with glomeruloid vascular proliferations.

Thymomas are usually found in the anterior mediastinum, the normal location of the thymus. Involvement of the pericardium by thymic tumors is seen in invasive or metastasized thymoma. Very rarely, thymomas arise primarily in the pericardium. These tumors are believed to derive from thymic tissue which was misplaced in the pericardium during embryologic development. In contrast to patients with orthotopic thymoma who commonly suffer from paraneoplastic diseases, especially myasthenia gravis, patients with intrapericardial thymoma manifestations mainly have symptoms of congestive heart failure which are caused by local complications of tumor growth. In this study, we present two cases of thymoma involving the pericardium. Both tumors were polygonal-oval cell thymomas. In one of the cases diagnosis of an entirely intrapericardial thymoma was established by autopsy. In the other case, explorative thoracotomy revealed massive pericardial and pleural tumor manifestations. The latter tumor showed a peculiar histological pattern with multiple glomeruloid bodies, a finding reported only once for thymomas.

Adult↗

[MR imaging of the thymoma--differentiation of invasive thymoma from noninvasive thymoma].

Magnetic resonance imaging (MRI) findings were reviewed in nine patients with histologically confirmed thymoma. The morphologic findings obtained by MRI were useful in distinguishing invasive from noninvasive thymoma. Invasive thymomas (2 cases) showed irregular contours and broad obliteration of the fatty plane between the mass and great vessels on T1-weighted coronary images. Perivascular infiltration shadow was considered to be characteristic of invasive thymoma. Noninvasive thymomas (7 cases) were round or oval in shape and showed slight obliteration of the fatty plane. In conclusion, MRI was helpful in differentiating invasive from noninvasive thymoma and defining the extent of thymoma.

Adult↗

Cytokeratin profiles of the thymus and thymomas: histogenetic correlations and proposal for a histological classification of thymomas.

AIMS: Since cytokeratins (CKs) are useful as differentiation markers for histogenetic and classification studies, we investigated the CK profiles of the thymus and thymomas in an attempt to understand the histogenetic correlation and to propose a histological classification. METHODS AND RESULTS: Nine thymuses and 34 thymomas were immunostained for various CKs of different molecular weights and involucrin. Based on cytomorphology and histoarchitecture, thymomas were classified into spindle cell (SC), small polygonal cell (SPC), mixed, organoid, large polygonal cell (LPC) and squamoid (SQ) thymomas for compiling CK profiles. The thymus was shown to comprise four epithelial compartments, each expressing a different CK profile. Different histological types of thymoma expressed different CK profiles. By correlating the CK profiles of the thymus and thymoma, SPC, SC and LPC thymomas appeared to be related to subcapsular, medullary and cortical cells, respectively. Organoid thymoma recapitulated the structure and CK profile of the normal thymus, while SQ thymoma acquired additional squamous type CK. The applicability and usefulness of the proposed histological classification were evaluated on 147 thymomas by correlating the results with their invasive behaviour. One hundred and thirty-nine cases (95%) could be classified and different histological types correlated strongly with their invasive behaviour. CONCLUSIONS: The thymus is a complex epithelial organ composed of heterogeneous cell types giving rise to various related histological types of thymoma. The results of the CK profile study supports the proposed histological classification, which is pathologically applicable and clinically useful in correlating with invasiveness. This cytomorphological classification, supported by the CK expression patterns, is comparable to Müller-Hermelink classification and the new WHO histological classification except that a separate group of SPC thymoma expressing only CK14 and CK19 was identified and separated from mixed thymoma.

Biomarkers, Tumor↗

Differential diagnosis between thymoma and non-thymoma by dynamic MR imaging.

PURPOSE: To evaluate the usefulness of dynamic MR imaging for differential diagnosis of anterior mediastinal tumors. MATERIAL AND METHODS: Fifty-nine patients with anterior mediastinal tumors were examined. According to histological diagnosis confirmed by surgery or biopsy, 31 had thymomas and 28 had non-thymoma lesions. The patients underwent dynamic MR imaging with gadopentetate dimeglumine administered as a bolus injection. Sequential images were obtained at 30-s intervals for 5 min. Significant differences in the mean peak times of time intensity curves (TICs) were found by histological type, using the Mann-Whitney test. RESULTS: The mean peak time of the TIC was 1.5 min in thymoma and 3.2 min in non-thymoma cases. The difference was statistically significant. Stages I and II of thymoma showed a mean value of 1.3 min, which was significantly shorter than that of 2.5 min in stage III. Differentiation of thymoma/non-thymoma based on the peak time of dynamic MR imaging showed optimal sensitivity (79%) and specificity (84%) when defining thymomas as lesions having peak time appearing earlier than 2 min and non-thymomas later than 2.5 min, with an accuracy of 81%. CONCLUSION: Dynamic MR imaging may improve the differential diagnosis between thymoma and non-thymoma and the staging of thymoma.

Adolescent↗

Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence?

BACKGROUND: Patients with MG often have other autoantibodies in addition to those against the acetylcholine receptor (AChR). It has been suggested that antibodies to the muscle protein titin may be diagnostic of a thymoma, but they have also been found in patients with late-onset MG. Antibodies to certain cytokines have also been detected in patients with MG and thymoma, and it is not clear whether these antibodies could be more useful clinically. The authors measured antibodies against titin and the cytokines interferon alpha (IFNalpha) and interleukin 12 (IL12) in patients with MG and thymoma or thymoma recurrence, and in patients with MG but without thymoma presenting before (early-onset MG) or after (late-onset MG) 40 years of age. METHOD: Levels of titin, IFNalpha, and IL12 antibodies were determined by radioimmunoassay in 191 patients with MG and 82 controls. RESULTS: As previously reported, titin antibodies were uncommon in patients with early-onset MG. However, in patients with late-onset MG, titin antibodies had similar prevalence and levels to those in patients with MG and thymoma, although the antibodies were uncommon in patients between 40 and 60 years of age presenting without a tumor. By contrast, cytokine antibodies were more common in patients with thymoma than in patients without thymoma, and cytokine antibodies typically increased substantially if the thymoma recurred. CONCLUSIONS: Measurement of titin antibodies has limited use in predicting the presence of a tumor, unless the patient is less than 60 years of age, but measurement of IFNalpha and IL12 antibodies may be helpful in identifying patients with a thymoma recurrence, particularly when mediastinal imaging is equivocal.

Adult↗

Histologic types of thymoma associated with pure red cell aplasia: a study of five cases including a composite tumor of organoid thymoma associated with an unusual lipofibroadenoma.

The histologic type of thymomas associated with pure red cell aplasia (PRCA) has generally been regarded to be predominantly the spindle cell type. The 5 thymomas associated with PRCA we studied showed various histologic types and none of them was a spindle cell thymoma. Some cases reported as spindle cell thymoma associated with PRCA in the literature might not be spindle cell type. The discrepancy could be due to the lack of consensus in the histologic classification of thymomas in the past. Our study showed that thymomas associated with PRCA lacked a strong correlation with a particular histologic type and the pathogenesis of PRCA associated with thymoma did not seem to be related to the histologic type. One of our cases was an unusual composite tumor of an organoid thymoma (WHO type B1) and a hitherto undescribed "lipofibroadenoma." The clinical outcome was influenced by the invasive character and the histologic type of the thymoma.

Adult↗

Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease.

Thymomas are the only tumors that are proven to generate mature T cells from immature precursors. It is unknown, however, whether intratumorous thymopoiesis has an impact on the peripheral T-cell pool and might thus be related to the high frequency of thymoma-associated myasthenia gravis. This study shows, using fluorescence-activated cell sorting-based analyses and T-cell proliferation assays, that thymopoiesis and T-cell function in thymomas correspond with immunologic alterations in the blood. Specifically, the proportion of circulating CD45RA(+)CD8(+) T cells is significantly increased in patients with thymoma compared with normal controls, in accordance with intratumorous T-cell development that is abnormally skewed toward the CD8(+) phenotype. Moreover, it is primarily the proportion of circulating CD45RA(+)CD8(+) T cells that decreases after thymectomy. The results also demonstrate that T cells reactive toward recombinant autoantigens are distributed equally between thymomas and blood, whereas T-cell responses to foreign antigen (ie, tetanus toxoid) are seen only among circulating T cells and not among thymoma-derived T cells. These functional studies support the hypothesis that thymopoiesis occurring within thymomas alters the peripheral T-cell repertoire. Because many thymomas are enriched with autoantigen-specific T cells, a disturbance of circulating T-cell subset composition by export of intratumorous T cells may contribute to paraneoplastic autoimmune disease arising in patients with thymoma. (Blood. 2000;96:3872-3879)

Adolescent↗

Hepatic metastatic thymoma and myasthenia gravis twenty-two years after the apparent cure of an invasive thymoma. A case report and review of the literature.

We report the case of a 62-year-old woman who presented in myasthenic crisis 22 years after radiation- and chemotherapy of an invasive thymoma which occurred during pregnancy. There was no evidence of recurrence of the thymoma at its original site, but an isolated hepatic metastasis was discovered. Biopsy of the mass revealed a spindle cell thymoma, whereas the original histology was that of a mixed round and spindle cell thymoma with moderate lymphocytic infiltration. The patient expired in spite of treatment with steroids, pyridostigmine bromide and plasma exchange on the one hand and cyclophosphamide with adriamycin on the other. To our knowledge, 22 years is the longest reported interval for the appearance of metastatic thymoma and myasthenia gravis after the diagnosis and apparent cure of a primary thymoma. This is also the only reported case of thymoma occurring during pregnancy but not associated with a rapidly fatal outcome.

Female↗

Thymoma with abundant L26-positive 'asteroid' cells. A case report with an analysis of normal thymus and thymoma specimens.

A case of thymoma is presented that was referred for consultation with the differential diagnosis of thymoma and non-Hodgkin's lymphoma. Immunoperoxidase studies performed on fixed, paraffin-embedded sections demonstrated the presence of numerous epithelial cells, supporting the diagnosis of thymoma. However, the pan-B-cell antibody L26 also demonstrated abundant staining, an unexpected finding that may be a potential source of diagnostic confusion. The L26 antibody stained cells with elongate cell processes that interdigitated between and surrounded thymocytes. We pursued this observation by performing immunoperoxidase studies on three thymoma and seven normal thymus specimens using fixed sections. Each thymoma had occasional cells or small clusters of L26-positive cells scattered throughout the neoplasm. In sections of normal thymus, L26-positive cells were also found, almost exclusively in the medullary regions. These cells tended to congregate around Hassall's corpuscles and had elongate cell processes that often surrounded medullary lymphocytes. Occasional small lymphocytes also appeared to be positive for L26. Our results demonstrate that cell populations that express B-cell antigens are consistently found in the thymic medulla and that these cells may be numerous in occasional thymomas. The presence of many L26-positive cells in a mediastinal mass should not dissuade one from making the diagnosis of thymoma if all other findings are consistent with that interpretation.

Aged↗

Immunohistological analysis of thymoma by molecules differentially expressed in the thymic cortex and medulla, and its application in the differential diagnosis of thymoma from esophageal and lung cancer.

The purpose of this study was to verify the WHO classification of thymic tumors using immunohistological methods, and to discover whether these methods can be applied to differentiate thymoma from squamous cell carcinoma (SCC) of the esophagus and the lung. Twenty-nine thymoma cases were classified according to WHO and were then immunohistologically examined for the positivity of these molecules. All thymoma cases investigated in this study were positive for IL-1R, and most of them were also positive for bek. In contrast, UH-1 was highly positive in B1 and B2 type thymomas, but negative or weakly positive in A, AB and B3 type thymomas. Twelve esophageal cancers and 21 lung cancers were also examined for the positivity of the same molecules. All esophageal cancers were negative for UH-1. Three of 12 cases were weakly positive for IL-1R, and four of these 12 cases were also weakly positive for bek. Twelve of 21 lung cancer cases were adenocarcinomas, all of them negative for IL-1R, bek and UH-1. Nine of 21 lung cancer cases were SCCs, all of them negative for UH-1. Eight of nine SCC cases were strongly positive for IL-1R, while seven of these were weakly positive for bek. We conclude that the WHO classification of thymic tumors is still valid as demonstrated by immunohistological analysis and that the positivity of UH-1, IL- 1R and bek might be helpful in differentiating thymoma from SCC of the esophagus and the lung.

Adenocarcinoma↗

Immunological findings in thymoma and thymoma-related syndromes.

Human thymoma is a neoplasm of thymic epithelial cells associated with several clinical syndromes ranging from autoimmune disease to immunodeficiency. The aim of our research was to investigate T cell-mediated immune response in patients with thymoma. Initially eight patients were enrolled in this study. Four patients underwent surgical removal of the thymus, while four were submitted to diagnostic procedures only. Inversion of the CD4:CD8 ratio was found in three patients. Only one subject displayed a normal CD19 count in peripheral blood. The mean value (+/-SD) of the CD19 percentage in the patient group was 2 +/- 2.2. Notably, the patients with thymoma had fewer mature B lymphocytes than the thymectomized patients. The T-cell receptor (TCR) repertoire was investigated in three individuals affected by thymoma: one underwent thymectomy, while the two others, one of which presented with lymphocytosis, were submitted to diagnostic biopsies only. The preliminary results showed a marked alteration in the CD8 repertoire of the thymectomized patient but not in that of the lymphocytotic patient. However, alterations in the TCR repertoire were also found in one patient with thymoma. Altogether, these preliminary findings reveal that loss of CD19+ lymphocytes in peripheral blood is a frequent phenomena in thymoma patients. In this article we discuss this aspect in the context of alterations of the TCR repertoire.

Adult↗

Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus.

Based on the light microscopical features of normal thymic epithelial cells, human thymoma was divided in different types, namely cortical, medullary, and mixed ones, according to the epithelial cell (EC) type. Lymphoid cell populations with morphological features of either cortical or medullary thymocytes were found according to different types of EC in thymoma. The histological variation of the different types of thymoma are demonstrated. In a retrospective study of 58 thymomas and 13 thymic carcinomas, malignant invasive character as well as the occurrence of myasthenia gravis were both found to be related to the neoplastic proliferation of the cortical epithelial cells, whereas in the usual mixed type of thymoma and the medullary type no gross invasion or metastases were noticed. These results are discussed in view of recent concepts and immunological findings of thymus microarchitecture.

Adolescent↗

Concurrent invasive thymoma and T-cell lymphoblastic leukemia and lymphoma. A case report with necropsy findings and literature review of thymoma and associated hematologic neoplasm.

Thymoma is associated with benign and neoplastic diseases. The authors report the concurrence of invasive thymoma and T-lymphoblastic leukemia/lymphoma in a 95-year-old man. The hematologic malignancy was suspected terminally, whereas the thymoma was discovered at necropsy. The lymphoblastic leukemia/lymphoma had a clonally rearranged T-cell receptor beta-chain gene and a mature thymocyte immunophenotype. No retroviral gene sequences (human immunodeficiency virus 1 and 2, and human T-cell leukemia virus 1 and 2) were identified by polymerase chain reaction and hybridization analysis. The association of thymoma with hematologic neoplasm is reviewed.

Abdominal Neoplasms↗

Pulmonary and pleural thymoma. Diagnostic application of lymphocyte markers to the thymoma of unusual site.

Two cases of the thymoma of the unusual sites were examined immunohistochemically. The one was intrapulmonary, and the other was diffuse pleural tumors. The infiltrating lymphocytes were T-cells showing OKT 6 positivity and nuclear immunoreactivity for terminal deoxynucleotidyl transferase (TdT) in the intrapulmonary tumor, like lymphocytes in the mediastinal thymoma of predominantly lymphocytic or mixed types. Although lymphocytes were dispersed in the pleural tumor, there were some TdT(+) OKT 6(-) lymphocytes and the similar finding was observed in the thymoma of predominantly epithelial type. In lung carcinomas and pleural mesotheliomas, there were no TdT(+) OKT 6(+/-) lymphocytes. Immunohistochemical studies using lymphocyte markers may be an useful tool for the diagnosis of the thymoma of ectopic site or unusual presentation.

Aged↗

A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma.

A clinicopathological study of surgically resected thymomas was performed using Masaoka's staging and modified Masaoka's staging systems, and the utility of these two staging systems was compared. The modification enabled adjustment for the disproportion in the number of cases between Stage I and Stage II. Analysis of survival rates, according to the tumor stage, indicated that the old classification should be reappraised, that is, division into non-invasive and invasive thymomas, although staging may contribute to the indication for postoperative radiotherapy, especially for Stage II disease. Analysis of the cases showed a wide spectrum of aggressiveness, varying from cases showing slow progression with a relatively favorable prognosis, such as the spindle cell type, to cases with rapid progression leading to tumor death in a relatively short time, such as the epithelial cell predominant and polygonal cell type. The pathological stage at the time of first surgical resection would reflect the degree of aggressiveness of thymoma in many instances. Therefore, not only staging the tumor extent but also grading of its aggressiveness are needed in order to predict the prognosis of patients with thymoma. For the latter, histology and cytopathology are helpful.

Adolescent↗

[Cyclosporin improved pure red cell aplasia associated with thymoma and tended to decrease thymoma size: a case report].

The case was a 56-year-old man who underwent extended thymothymectomy in 1993 because of an invasive thymoma classified as Masaoka IIa. The tumor was disseminated through the right thoracic cavity in 1994. Although the chemotherapy was repeated, the disseminated thymoma tended to increase in size. The patient was suffering from severe anemia, and pure red cell aplasia was diagnosed in September 2002. The administration of cyclosporin was initiated, and not only brought about improvement of pure red cell aplasia but also tended to shrink the thymoma. Cyclosporin may be an effective drug for the reduction of thymoma as well as for pure red cell aplasia.

Cyclosporins↗