PMC8155543_01
Comparison of findings from biopsy of the primary lung tumor and metastatic brain tumor. Hematoxylin and eosin staining (HE x40) of the primary lung adenocarcinoma was positive for ROS1 and PD-L1 (> 90%) by immunohistochemical (IHC x40). The metastatic brain tumor showed poorly differentiated carcinoma by HE, which was partly positive for ROS1 and PD-L1 (40%) by IHC. ROS1 rearrangement was confirmed by FISH (>15% of the cells demonstrate split or single 3' signals).
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ROS1 and PD-L1 (> 90%) but negative for anaplastic lymphoma kinase (ALK) ( Figure 1 ). ROS1 rearrangement was then confirmed by fluorescence in situ hybridization (FISH) ( Figure 1 ).
Schematic diagram of the course of the patient's disease. Imaging before treatment showed a lung mass in the right middle lobe and left frontal lobe metastasis. After administration of crizotinib, the primary tumor size shrank; however, left frontal lobe metastasis was larger.
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A repeated brain-MRI showed rapid brain tumor progression, severe brain edema, and cerebral midline deviation ( Figure 2 ).
MMNG HOS transforming gene (MET) amplification test by fluorescence in situ hybridization (FISH). MET is represented by a single red dot, and centromere probe of chromosome 7 (CEP7) is represented by a single green dot. Amplification test by FISH revealed no MET amplification (MET/CEP7 ratio <2.0 and MET per cell<5) in the primary lung tumor per-crizotinib but a cluster MET amplification (MET/CEP7 ratio >=2.0 and MET per cell>=5) in the metastatic brain tumor post-crizotinib.
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FISH demonstrated a cluster of MET signals congruent with the NGS result ( Figure 3 ). To investigate whether MET amplification was acquired after TKI treatment, the primary lung lesion was reanalyzed by FISH, and the result was negative for MET amplification ( Figure 3 ).