Pneumonitis in patients with thymoma and Good's syndrome

Background: The association between thymoma (T) and immunological dysregulations is well acknowledged. Good's syndrome (GS), which occurs in approximately 6% to 11% of T patients, is characterized by hypogammaglobulinemia, few or absent B-cells (CD19+), CD4 T cells lymphopenia, abnormal CD4/CD8 T ratio and impaired T cell mitogenic response. Patients with GS have increased susceptibility to bacterial, opportunistic and viral infections related to both humoral and cell-mediated immunodeficiency. The recent Sars-Cov-2 pandemic drew attention to the clinical condition of fatal viral pneumonitis and cytokines storm. Here we reported our monocentric experience of pneumonitis in patients with T and GS before the Sars-Cov-2 pandemic. Methods: We conducted a retrospective analysis of T patients with associated GS referred to the Rare Tumours Reference Center of University Federico II of Naples over a 10-year period (from 2009 to 2019). All the patients with radiological and/or clinical pneumonitis diagnosis were evaluated for this report. Immunological features, histopathological diagnosis and clinical outcome were registered. Results: A total of 41 patients with T and GS were identified, including 17 patients with local disease (stage I-II according to Masaoka-Koga) and 24 with advanced disease (stage III-IV). The majority (56.3%) had B2 T diagnosis. Radiological and/or clinical pneumonitis diagnosis was assessed in 23 cases (56%). Viral pneumonitis was detected in 8 patients: 3 patients with H1N1 infection, 3 patients with CMV infection, 2 patients with EBV infection. Bacterial pneumonitis was diagnosed in 9 patients (3 patients with K. pneumoniae, 4 patients with S. aureus, 2 patients with H. influenza). Opportunistic pneumonitis was found in 2 patients with Aspergillosis infection. In 2 cases no pathogenic agent was identified. The immunophenotyping, assessed in 4 patients with viral pneumonitis, displayed very low/undetectable levels of B cells, with median % value of CD3+T cells and NKT of respectively 9.8% and 0.4% of the total leukocytes. The median % of Treg was 4.7%. CD4+/CD8+ ratio was variable, ranging from 1,2 to 0,6. Interestingly the number of B cells was extremely low, independent of CD4+/CD8+ ratio. Blood levels of cytokines, chemokines and growth factors revealed elevated IL-4, Eotaxin, CCL2 / MCP-1 and CCL5 / RANTES ad strong reduction of IL-10. PDGF-BB levels were also elevated. 15 patients required admission to intensive care Six patients died for fatal pneumonitis. Conclusions: The management of T patients with GS is extremely challenging. Clear diagnostic algorithms do not yet exist and immune-profiling and quantitative immunoglobulins should be considered a part of diagnostic search in these patients. The coexistence of cancer, infections and immunosuppression may trigger lifethreatening conditions, such as fatal pneumonitis, which often require intensive care and multidisciplinary approach.