case_images: PMC10477974_01
case_images: Changes in imaging throughout the treatment period. (A-D) CT scans of the chest at different times. (E-H) CT scans of the abdomen at different times. (I) Timeline of treatment process. Red arrow: the location of the tumor lesion.
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case_images: On November 5th, 2021, a chest computed tomography (CT) scan showed two nodules in the medial segment of the middle lobe of the right lung (the larger one was about 15x20mm), and there were enlarged lymph nodes in the right hilar and mediastinum (the larger one was 30x33mm), which was considered to be lung cancer around the middle lobe of the right lung and lymph node metastasis in the right hilar and mediastinum ( Figure 1A ). The abdominal enhanced CT in November 9th, 2021 showed multiple low-density space-occupying lesions of different sizes in the liver, with the largest lesion located in the S8 segment of the liver, about 105x112mm in size ( Figure 1E ). In addition, there were other low-density occupying sites in the liver, and the diameter of the larger lesion was about 20mm. ( Figure 1E ). The main clinical diagnosis and treatment process of the patient is shown in  Figure 1I . TTF1 (weak positive), CK19, Ki-67 (about 20%+), CD10, MUC-1, GATA-3, and negative for CK20, NapsinA, hepatocyte marker, Arginase-1, Glypican3, CD34, ER ( Supplementary Figure 1 ). The light microscopic morphology and immunohistochemical results tended to be ICC. In addition, IHC for PD-L1 was negative (TPS<1%, CPS<1) ( Supplementary Figure 1 ). CT scan conducted approximately 1 months after treatment onset on January 11, 2022 demonstrated obvious tumor regression, compared with the results on November 5th, 2021, with a decrease in nodule in the medial segment of the middle lobe of the right lung from 15x20 mm to 12x15 mm, and lymph node in the right hilar and mediastinum from 30x33mm to 20x15 mm ( Figure 1B ). Compared with November 9, 2021, the lesion at the S8 segment of the liver was reduced from 105x112mm to 69x96mm, and other low-density space occupying lesions in the liver were reduced from 20mm to 12mm ( Figure 1F ). Specifically, the nodule in the medial segment of the middle lobe of the right lung was reduced from 12 x 15 mm to 5 x 3 mm, lymph node in the right hilar and mediastinum was reduced from 20x15 mm to 13x12 mm ( Figure 1C ), and the lesion at the S8 segment of the liver was reduced from 69x96mm to 58x75mm ( Figure 1G ). Therefore, the patient continued to receive ensartinib, and follow-up CT examination was carried out on June 12, 2022, the results showed that the patient maintained PR status ( Figures 1D, H ). The main clinical diagnosis and treatment process of the patient is shown in  Figure 1I .
case_images: Pathological examination of the liver biopsy and immunohistochemical staining of ALK expression. (A) The pathological examination showed poorly differentiated adenocarcinoma. Hematoxylin and eosin (H&E) stain. Magnification: 40x. (B) The immunohistochemical result showed positive for ALK (D5F3). Magnification: 40x. ALK, anaplastic lymphoma kinase.
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case_images: Ultrasound-guided needle biopsy of liver mass was performed in November 17th, 2021, the pathological results were considered to be poorly differentiated adenocarcinoma ( Figure 2A ). The mucous membranes of cecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum were smooth, the blood vessels were clear, and no abnormal secretions, new organisms or erosions were found ( Supplementary Figure 2A ). Gastroscopy showed no obvious lesions ( Supplementary Figure 2B ). Another liver biopsy was performed on December 15th, 2021, and IHC results showed positive for ALK (D5F3) ( Figure 2B ).