PMC9110816_01
Panel (A) Brain MRI scan at admission showing T2-fluid attenuated inversion recovery (FLAIR)-weighted multifocal hyperintense white matter lesions with diffusion-weighted imaging (DWI, narrowed windowing for clarity purpose) ill-defined hyperintense edges and hypointense core in keeping with disease activity. Panel (B) Brain MRI scan 1 year after treatment initiation showing regression of the T2/FLAIR hyperintense lesions and disappearance of the DWI (narrowed windowing) hypersignal, in keeping with gliosis (ADC not shown). Note progressive brain atrophy in previously affected areas. Panel (C) Patient's clinical course and evolution of JC viral load in the cerebrospinal fluid (CSF) over time. JC virus PCR assay's quantification limit is 500 copies/ml; detection limit is 75 copies/ml.
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On diffusion-weighted imaging (DWI), these lesions exhibited typical ill-defined hyperintense edging and hypointense core suggestive of an active-stage disease (Figure 1A and Supplementary Figure S1). CSF JCV load was considerably reduced to 1870 copies/ml (Figure 1C) and brain MRI was stable, without any enhancement after gadolinium injection. CSF JCV load reduced accordingly and was even below the PCR's detection limit (75 copies/mL) 9 months after treatment initiation (Figure 1C). Brain MRI showed regression of the extent of the T2-FLAIR lesions and disappearance of DWI signs of disease activity (Figure 1B and Supplementary Figure S1).
Panel (A) Chest CT performed before treatment initiation showing a 14-mm right upper lobe irregular nodular lesion. Panel (B) This lesion was found to be hypermetabolic on [18F]-fluorodeoxyglucose positron emission tomography. Panel (C) Lung biopsy specimen showing a modified fibrous tissue infiltrated by irregular and ramified tubuloacinar structures formed by non-small neoplastic cells with hyperchromatic nucleus and weakly eosinophilic cytoplasm. The overall appearance is compatible with a lung adenocarcinoma (hematoxylin-eosin stain, 200x). Panel (D) PD-L1 is expressed by 50% of tumor cells (PD-L1 immunoperoxydase, 200x). Panels (E, F) Chest CT performed (E) 6 months and (F) 1 year after treatment initiation showing stability of the lesion.
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Whole-body [18F]-fluorodeoxyglucose positron emission tomography (18FDG-PET) and associated chest computed tomography (CT) revealed a 1.4 cm hypermetabolic nodular and irregular mass located at the lateral edge of the right upper lobe associated with ipsilateral hilar, paratracheal and subcarinal hypermetabolic lymphadenopathy (Figures 2A, B). Lung CT-guided biopsy was performed, and pathological analyses were consistent with the diagnosis of lung adenocarcinoma (Figure 2C). PD-L1 was expressed by 50% of tumor cells (Figure 2D). In parallel, detection of PD1 on the patient's peripheral CD8+ and CD4+ T cells, which was noticeably high while compared to the healthy control subject, as well as detection of T cell immunoreceptor with Ig and ITIM domain (TIGIT), another inhibitory immune checkpoint, decreased with atezolizumab treatment (Supplementary Figure S2). Regarding lung adenocarcinoma, repeated thoracic-abdominal-pelvic CTs demonstrated a stable disease (Figures 2E, F).