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  • Title: Pathological aspects of malignant and benign thymic disorders.
    Author: Müller-Hermelink HK, Marx A.
    Journal: Ann Med; 1999 Oct; 31 Suppl 2():5-14. PubMed ID: 10574149.
    Abstract:
    A WHO committee recently defined criteria for distinguishing between thymic epithelial tumours (TET) and classified them as type A, AB, B1-3 and C thymomas. As the terminology for each WHO type is still controversial, it is recommended to use also other names in addition to the WHO classification to allow comparability of future clinicopathological studies. We consider type A and AB thymomas (medullary and mixed thymomas) clinically benign, whereas type B1-3 thymomas (predominantly cortical and cortical thymomas and well-differentiated thymic carcinomas) are of low-grade malignant potential and most type C thymomas (category II malignant thymomas) are highly malignant. Not yet approved by the WHO are the recently described 'thymoma with pseudosarcomatous stroma' and the 'low-grade metaplastic carcinoma of the thymus', which are considered as benign or low-grade malignant tumours, respectively. Thymic pathology frequently occurs in myasthenia gravis (MG). Production of autoantibodies against the acetylcholine receptor results from an antigen-driven immune reaction that starts inside the thymus, is maintained there but spreads to extrathymic sites already during the early phase of MG. Paraneoplastic MG occurs only in type A, AB and B1-3 thymomas. Abnormal TET microenvironments trigger nontolerogenic T-cell selection by neoplastic epithelial cells. Only after export of substantial numbers of naive, potentially autoreactive T cells to extratumorous sites does T-cell activation outside the thymoma initiate the autoimmune process. Early surgery after onset of MG is essential in thymitis to prevent substantial export of autoreactive T cells from the inflamed thymus to extrathymic organs, and it usually alleviates MG symptoms. In thymoma, 'dissemination' of autoreactive T cells to extratumorous sites has already continued for many months or even years before emergence of symptoms of MG. Therefore, thymoma surgery is aimed against oncological and local cardiovascular complications and rarely succeeds in alleviating symptoms of MG.
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