PMC9403065_01
Schematics timeline showing the patient treatment history. The computed tomography (CT) and magnetic resonance imaging (MRI) scan at different clinical time points as shown. Red arrows: location of the primary lung lesion in different scans. Green arrow: location of the metastasis lumbar lesion in different scans.
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Follow-up MRI on March 2, 2020, showed that the soft tissue of metastasis lesions around the lumbar spine reduced significantly, while CT showed that the primary lung lesion was slightly enlarged ( Figure 1 ). Strikingly, a routine CT on 21 April 2020 showed a significant enlargement of the primary focus after the injection of PCV ( Figure 1 ).
Pathological assessment of the primary lung lesion and metastasis lesion after radiotherapy. (A) Representative biopsy scan of primary lung lesion by HE (hematoxylin and eosin) staining. (B) Representative biopsy scan of lumbar bone marrow with Ki67 and ALK antibody by IHC (immunohistochemistry) staining.
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Hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining showed that the primary lung lesion was mainly composed of map-like necrosis ( Figure 2A ), while there was a small amount of ALK-positive tumor cells that remained in the lumbar bone marrow of metastasis lesion ( Figure 2B ). Pathologically, multifocal granulomas were formed in the primary pulmonary lesion, with thin-walled capillaries and proliferative fibroblasts on the edge of the tumor bed and peripherally infiltrating immune cells around the central necrosis ( Figure 2A ). In addition, early tertiary lymphoid structures (TLSs) were formed in the primary lesion ( Figure 2A ).
Spatial cell cluster analysis of the primary lesion scanned by Hyperion imaging mass cytometry. (A) The area selected for Hyperion tissue imager scan on a 5 mm x 5 mm formalin-fixed, paraffin-embedded tissue slide. (B) Cell cluster analysis of the specimen. t-SNE descending dimension map of different cell types. (C) Imaging mass cytometry showing that the primary lesions in the lung were necrotic and infiltrated by multiple types of immune cells.
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T cells, CD68+ tissue macrophage cells, and CD16+ natural killer (NK) cells ( Figures 3A-C ). These results indicated that the primary lesion experienced a robust immune response.