PMC9869796_01
Representative upper abdominal imaging throughout the treatment period. (A) Preoperative CTA showed a lumpy mixed-density lesion in the liver with an unclear boundary with the gallbladder. (B) CT showed tumor cells was partially necrotic after D-TACE. (C) Postoperative CT showed new nodules in the S6 segment of the residual liver. (D) CT showed two small nodules in the S6 segment of the liver. (E) CT showed some shadows were smaller than before after palbociclib treatment. (F) CT showed a tumor reduction (reaching the criteria for a PR according to RECIST 1.1). (G) The latest CT showed the sign of recurrence. (H) The main clinical diagnosis and treatment process.
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A computed tomography angiography (CTA) of the upper abdomen showed a lumpy mixed-density lesion in the left lobe of the liver with an unclear boundary with the gallbladder (Figure 1A). Compared with the examination result in May 2020, the abdominal computed tomography (CT) on July 10, 2020, revealed the mass of the left lobe of the liver showed annular enhancement as before, and there were several small cystic areas without enhancement between the right lobe of the liver (Figure 1B). On July 29, 2020, the postoperative CT examination revealed new nodules in the S6 segment of the residual liver, which suggested the possibility of intrahepatic metastasis (Figure 1C).  An enhanced CT scan of the upper abdomen on October 10, 2020, showed two small nodules in the S6 segment of the liver, with a diameter of about 7-12 mm (Figure 1D), suggesting that the patient might have undergone metastasis. Enhanced CT scan of the upper abdomen on March 8, 2021, showed that, compared with the CT result on October 10, 2020, there were several clusters of low-density shadows in the liver, with a maximum size of about 27 mmx17 mm, some of which were smaller than before and none of which had enhanced (Figure 1E). And a follow-up CT scan of the upper abdomen on July 12, 2021, showed that, compared with the CT result on March 8, 2021, there were several clusters of low-density shadows in the liver, with a maximum size of about 17 mmx10 mm, some of which were smaller than before, and no enhancement was observed (Figure 1F). At the latest follow-up on July 21, 2022, CT scan showed that there were multiple slightly low-density nodules in the liver, suggesting that the patient had a recurrence of the disease (Figure 1G). The main clinical diagnosis and treatment process of the patient is shown in Figure 1H.
Excised tissue and postoperative pathological examination of the patient. (A) Excised gallbladder and liver tissue: a gray mass of 6 cm x 4.5 cm x 3 cm in size on section view. (B) Pathological examination: hematoxylin and eosin (H&E) stain, original magnification x200. (C) Immunohistochemical results: CK7 (+); CK19 (+); CK20 (-); CDX-2 (-); Glypican-3 (-); Hepatocyte (-); TTF-1 (-).
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II (cT2N0M0) ICC (Figure 2), which was moderately differentiated, with no intratumoral tumor plug and nerve fiber invasion, no satellite nodules, and no involvement of liver capsule and liver resection margin. Immunohistochemical staining indicated the sample being positive for CK7 and CK19, and negative for CK20, CDX-2, TTF-1, glypican-3, and hepatocyte marker.
Copy number analysis of all genes showing the CDKN2A/B loss. The horizontal axis represents the location of the gene on the chromosome, and the vertical axis represents the copy number calculated by the NGS method.
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CDKN2A and CDKN2B genes (CDKN2A/B loss, Figure 3). CDKN2A and CDKN2B encode the p16INK4a and p15INK4b proteins, respectively, both of which are inhibitors of CDK4/6 kinases.