Thymoma and paraneoplastic myasthenia gravis

Abstract

Paraneoplastic autoimmune diseases associate occasionally with small cell lung cancers and gynecologic tumors. However, myasthenia gravis (MG) occurs in at least 30% of all patients with thymomas (usually present at MG diagnosis). These epithelial neoplasms almost always have numerous admixed maturing polyclonal T cells (thymocytes). This thymopoiesis-and export of mature CD4(+)T cells-particularly associates with MG, though there are rare/puzzling exceptions in apparently pure epithelial WHO type A thymomas. Other features potentially leading to inefficient self-tolerance induction include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatibility complex class II molecules in thymomas, absence of myoid cells, failure to generate FOXP3(+) regulatory T cells, and genetic polymorphisms affecting T-cell signaling. However, the strong focus on MG/neuromuscular targets remains unexplained and suggests some biased autoantigen expression, T-cell selection, or autoimmunization within thymomas. There must be further clues in the intriguing serological and cellular parallels in some patients with late-onset MG but without thymomas-and in others with AIRE mutations-and in the contrasts with early-onset MG, as discussed here.

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

“…Approximately 70 % of patients with MG with anti-AChR antibodies have thymic follicular hyperplasia, approximately 10 % have thymomas, and the remainder have a histologically normal or atrophic thymus gland [4,13,14]. The alterations of the immune system that occur with thymic hyperplasia versus thymoma are quite distinct.…”

“…These tumors commonly express self-antigens such as the AChR and the large muscle protein, titin. Naïve effector T cells with AChR or titin reactivity may escape negative selection due to the abnormal thymic microenvironment created by the thymoma [14]. Alternatively, autoimmunization may actually occur in the thymus owing to expression of AChR by the tumor and the [20].…”

Thymome

“…3. Eine Myasthenia gravis kommt in 20-40 % der Fälle vor, auch andere Autoimmunerkrankungen sind häufig [12].…”

“…Eine Myasthenia gravis kommt in 50 % der Fälle vor, andere Autoimmunerkrankungen (z. B. eine Hypogammaglobulinämie) sind selten (5 % [12,22] …”

“…"Reine" B3-Thymome sind seltener als Thymome, die neben B3-Arealen auch Areale mit B2-und (seltener) B1-Morphologie zeigen [22]. Eine Myasthenia gravis (MG) kommt in 40 % der Fälle vor, andere Paraneoplasien sind selten [12]. Hassall-Körperchen kommen selten vor, medulläre Inseln fehlen (.…”