PMC6369846_01
Chest computed tomography and histopathological findings of the primary lung tumor.. Note: (A) Chest computed tomography revealed a nodule in the upper-left lung; (B) a diagnosis of pathological lung adenocarcinoma was considered (H&E stain).
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After pulmonary computed tomography (Figure 1A) and magnetic resonance imaging (MRI) of the head in hospital, the patient was assessed as being acceptable for surgery, without distant metastasis. Postoperative pathology showed a diagnosis of moderately differentiated lung adenocarcinoma in his upper-left lung (Figure 1B).
Pulmonary CT and MRI screening findings of the lung tumor and brain metastasis (A and B).. Note: (A) Pulmonary CT indicated multiple metastases in lung; (B) MRI screening showed multiple metastases in brain metastasis.. Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging.
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Pulmonary CT and MRI screening showed multiple metastases in both lungs and brain metastasis, respectively (Figure 2A and B).
Next-generation sequencing and ALK immunohistochemistry findings of the primary lung-tumor-tissue samples.. Notes: (A) A new fusion form of ALK rearrangement involving inversion of the NCOA1 gene (exons 1-12) and the ALK gene (exons 20-29) was identified. (B) Heterozygous genetic polymorphisms were discovered: CDAK27Q, ERCC1N118N, DPYDI543V, MTHFRA222V, and GSTP1I105V. A homozygous deletion polymorphism was discovered in the GSTT1 and TYMS genes (-6 bp/-6 bp). (C) Immunohistochemistry results indicated ALK rearrangement was positive. Magnification x200.
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To explore potential targeted therapies, next-generation sequencing was performed in tumor tissue and revealed a new type of ALK arrangement (NCOA1-ALK, Figure 3A). Mutation profiling of this patient is summarized in Figure 3B, and expression of the ALK protein was confirmed by immunohistochemistry (Figure 3C).
Evolution at follow-up of the patient's lung tumor (A-E) and brain metastasis (F-J) during crizotinib treatment.. Notes: (A) Baseline chest CT (October 2016) showed multiple metastatic nodules in the right lung before crizotinib treatment; (B-D) multiple metastatic nodules in the right lung decreased significantly and the brain-lesion metastases were stable in several follow-up visits on chest CT; (E) chest CT examination indicated multiple metastatic nodules having almost disappeared (April 2018); (F) intracranial metastasis before crizotinib treatment on MRI (September 2016); (G-I) lesions of intracranial metastasis had remained stable in several follow-up visits during crizotinib treatment; (J) MRI indicated lesions of intracranial metastasis had remained stable (May 2018).. Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging.
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After 2 months of crizotinib treatment, the multiple metastatic nodules in the right lung had decreased significantly (Figure 4A and B) and the brain-lesion metastases were stable (Figure 4F and G). Several follow-up visits were recorded, and the patient was still alive without disease progression in lung lesions (Figure 4C-E) or brain metastases (Figure 4H-J).