Immunological presentations and clinical features associated with Thymic Malignancies: The potential role of histological classifications and tumour grading on the future recurrence of opportunistic infections and paraneoplastic autoimmune conditions

Abstract

Thymic malignancies are rare cancer tumours of the thymus arising from thymic epithelial cells and are characterized by a highly diversified clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent presentations of associated paraneoplastic autoimmune syndromes. Myasthenia Gravis (MG) is the most prevalent of such autoimmune conditions, presenting in roughly half of thymoma patients, and is associated with substantial hyperactivation of T lymphocytes, highly dysregulated negative and positive T lymphocyte selection, leading to a systemic imbalance of the immune system, and consequently aiding and abetting the manifestation of severe opportunistic infections and multiple autoimmune comorbidities such as Pure Red Cell Aplasia and Good's syndrome. Although the clinical, immunological and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumour staging and histological gradings on the occurrence and recurrence of infections and multiple autoimmune comorbidities. The current study aimed to interrogate the role of WHO thymoma classification criteria and Masaoka staging on the recurrence of severe opportunistic infections and the presentation of multiple paraneoplastic autoimmune syndromes post-thymectomy. The current study collected clinical and immunological data from 109 patients suffering from both MG and a pathologically proven thymoma. Statistical analysis of the collected data yielded significant associations between different stages of Masaoka grading and WHO classification on the number of autoimmune comorbidity and presence of severe recurrent infections, leading to the conclusion that early histological gradings and tumour infiltration patterns play a significant role in predicting future immunological behaviour, clinical outcomes, and susceptibility to recurrent infections. Future studies must further investigate the role of autoimmunity, its associated antibody expression profiles and thymic tissue pathology. Furthermore, novel therapeutics must further explore the role of emergent immunotherapeutics, such as adoptive cell therapies, as a viable patient-stratified treatment strategy for thymic malignancies.