Autoimmune disorders and paraneoplastic syndromes in thymoma

Abstract

Thymomas are counted among the rare tumour entities which are associated with autoimmune disorders (AIDs) and paraneoplastic syndromes (PNS) far more often than other malignancies. Through its complex immunological function in the context of the selection and maturation of T cells, the thymus is at the same time highly susceptible to disruptive factors caused by the development and growth of thymic tumours. These T cells, which are thought to develop to competent immune cells in the thymus, can instead adopt autoreactive behaviour due to the uncontrolled interplay of thymomas and become the trigger for AID or PNS affecting numerous organs and tissues within the human body. While myasthenia gravis is the most prevalent PNS in thymoma, numerous others have been described, be they related to neurological, cardiovascular, gastrointestinal, haematological, dermatological, endocrine or systemic disorders. This review article sheds light on the pathophysiology, epidemiology, specific clinical features and therapeutic options of the various forms as well as courses and outcomes of AID/PNS in association with thymomas.Whenever suitable and backed by the limited available evidence, the perspectives from both the thymoma and the affected organ/tissue will be highlighted. Specific issues addressed are the prognostic significance of thymectomy on myasthenia gravis and other thymoma-associated AID/PND and further the impact and safety of immunotherapies on AID and PND relating to thymomas.

An unusual presentation of thymoma: dysgeusia, ulcerative colitis, keratoconjunctivitis sicca, autoimmune retinopathy and myasthenia gravis

“…The prevalence of Sjogren’s disease in patients with thymoma is reported as low as 0.46%, with mixed outcomes following thymectomy 15 16. There have been additional reports of keratoconjunctivitis sicca related to thymoma; however, ocular outcomes were not reported following thymectomy 3. It is likely that such non-specific symptoms are underdiagnosed and thus not reported.…”

“…They are deemed to be autoimmune phenomena rather than manifestations of direct invasion by the primary tumour, and the pathophysiology, particularly in relation to thymomas, is complex and likely multifactorial 1 2. The thymus is an essential organ in the development of central immune tolerance, and dysregulation appears to trigger a high prevalence of associated PNS, far more so than other malignancies 1 3. Thymomas are deemed to present with PNS in approximately 50% of cases; up to 40% may present with myasthenia gravis (MG), and over 15% present with PNS other than MG 1 2.…”

Molecular pathology of thymomas: implications for diagnosis and therapy

“…Thymomas are unique tumors due to their almost consistent non-tolerogenic, intratumorous thymopoiesis that is almost never encountered in TCs and not in other carcinomas. This feature is likely the major pathomechanism that leads to the unprecedented frequency of autoimmune phenomena (about 80%) and autoimmune diseases (about 40%) in patients with thymoma but not in patients with other malignancies [7]. Among the autoimmune targets, striated muscle proteins prevail as reflected by the fact that myasthenia gravis (MG) due to autoantibodies to the Acetylcholine Receptor (AChR) and striational autoantigens (e.g., Titin, skeletal and cardiac Ryanodine Receptors (RYRs)) is the leading thymomaassociated autoimmune disease [8].…”

“…Among the autoimmune targets, striated muscle proteins prevail as reflected by the fact that myasthenia gravis (MG) due to autoantibodies to the Acetylcholine Receptor (AChR) and striational autoantigens (e.g., Titin, skeletal and cardiac Ryanodine Receptors (RYRs)) is the leading thymomaassociated autoimmune disease [8]. However, almost any other organ-specific (e.g., thyroid, hepatic, renal) and systemic autoimmune disease (e.g., SLE, RA) can occur either in isolation or combined with MG or other autoimmune diseases [7,9]. The pathogenesis of most thymoma-associated autoimmune diseases is unknown.…”

Thymic tumours: a single center surgical experience and literature review on the current diagnosis and management of thymic malignancies

“…While MG is the most common one, a wide range of other autoimmune paraneoplastic diseases has been reported. Among them common findings are pure red cell aplasia (PRCA) and hypogammaglobulinemia (20,21).…”