PMC7768075_01
The pathophysiologic process that produces the immune-related storm in thymoma has not yet been fully clarified. Some possible vicious cycles involve enhanced T-cell activity against antigens present in the thymus and in the "innocent" bystander organs, whereby growing amounts of preexisting autoreactive T-cells are unleashed from the medulla, breaking the immune-equilibrium existing in the normal thymus. In particular, the immature CD4+CD8+ double positive cells move to single positive CD4+ helper T-cells (binding MHC class II) and CD8+ cytotoxic T-cells (binding MHC cIass I) involved in the adaptive immunity while a negative selection leads to apoptosis of self-reacting T clones. In thymic neoplasia the immature thymic lymphocytes may escape quality control by DC prompting T-cell hyperactivation and autoimmune manifestations. DC, dentritic cell; APC, antigen presenting cell; MHC, major histocompatibility complex.
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TSH 0.013 mcUI/ml (normal range 0.3 to 4.2 mcUI/ml). Flow cytometric analysis was performed to study lymphocyte subpopulations. T-cells contained a predominant T-cytotoxic lymphocyte (CD3+, CD8+) population, along with low levels of natural killer T (NKT) cells and B-cells ( Supplementary Figure 1 ).
(A) Hematoxylin-eosin (HE) immunostaining (IHC): fibrous septa within the tumor separate the lymphoepithelial elements (4x); (B) HE IHC: aggregates of large epithelial cells with a clear cytoplasm interspersed between lymphoid cells (20x); (C) CK 19 IHC: dense epithelial cell network (10x); (D) PD-L1 IHC (Clone 22 C3): Membranous positivity of the epithelial cells (20x); (E) TdT IHC: lymphocytes consist predominantly of immature T-cells; (F) CD8 IHC: immune-positivity of CD8 on immature lymphocytes (10x).
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T-cell population expressing TdT (presumed CD4, CD8 double positive) and PD-1 at baseline ( Figure 2 ). Therefore, off-label medication with Pembrolizumab was required due to the failure of previous lines of chemotherapy and lack of other standard medications with proven effectiveness.
Biochemical and laboratory findings trend over time. The normal value (dotted line) refers to the unit, representative of the referral value to whom each fold change is referring to. MMF, mycophenolate mofetil.
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Remarkably, early increased lymphocyte counts paralleled the exponential liver enzymes increase ( Figure 3 ).
Longitudinal slices of computed tomography scans at baseline (A) and post treatment (B) showed a decrease of the mediastinum mass with intralesional hypondensity (red arrows) and pleural nodules (yellow arrows), defined as partial response according to iRECIST criteria.
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Computed tomography scan revealed a partial response according to RECIST criteria, with a decrease of the mediastinum mass and pleural nodules ( Figure 4 ).