PMC8484748_01
Timeline and PET-CT examination. (A) Indicates initial diagnosis, medication treatment, surgery, and follow-up timeline of the patient. (B) Shows a large mass in the right lobe of the liver with increased radioactive uptake of the solid component. (C) Shows multiple enlarged lymph nodes adjacent to the abdominal aorta with increased radioactive uptake. (D) Shows increased nodular radioactive uptake in the inferior vena cava. (E, F) Show anterior costal diaphragm nodule and right diaphragmatic nodule with increased radioactive uptake.
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Positron emission tomography-computed tomography (PET-CT) scans showed a huge mass with uneven increased metabolism in the right lobe of the liver, increased metabolism of the inferior vena cava nodule, increased metabolism of the right diaphragmatic nodule, and hypermetabolic lymph nodes near the abdominal aorta and anterior costal diaphragm (Figures 1B-F).
Hematoxylin-eosin (HE) staining and immunohistochemical analysis of liver tumor tissue from the needle biopsy. Pathological images show (A) HE staining (200x), (B) positive CK19 staining, (C) negative AFP staining, and (D) negative hepatocyte staining. (E) Immunohistochemical staining for PD-L1 expression (200x). Multiple fluorescence immunohistochemical images show (F) the CD8+T cells, (G) the natural killer (NK) cells, (H) the macrophages, and (I) the merged images of the previous three images.
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The pathohistological analysis of the tumor revealed poorly differentiated adenocarcinoma with necrotic components (Figure 2A). AFP and hepatocyte (Figures 2C, D), predisposed to cholangiocarcinoma. All indications suggested a diagnosis of stage IV iCCA (T2N1M1) according to the American Joint Committee on Cancer (AJCC) Cancer Staging Handbook,8th edition. T cell, natural killer (NK) cells, and macrophages (Figures 2F-I). The density of these infiltrated lymphocytes at the tumor core were 1594 cells/mm2, 986 cells/mm2, and 3980 cells/mm2 respectively. The tumor proportion score (TPS) of the PD-L1 expression level was 70% according to Allred criteria using the 22C3 monoclonal mouse anti-human PD-L1 antibody (Figure 2E).
MRI evaluation during preoperative systemic treatment. (A-C) indicate the maximum diameter of the lesion located in the liver, the maximum diameter of the lesion in (A-C) were 10.16cm, 8.93cm, and 8.77cm. (D-F) indicate the lesion located in the tumorigenic thrombus of the inferior vena cava, the maximum diameter of the lesion in (D-F) were 3.92cm, 3.28cm, and 3.00cm. Arrows in the figures indicate the position of lesions.
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After treatment with sintilimab (200 mg q3W) and lenvatinib (8 mg qd) for 7 cycles (21 weeks), MRI showed that the lesions in the right hepatic lobe and inferior vena cava had significantly decreased in size (Figure 3).
Images of the operation and the MRI reexamination after surgery. (A) shows the inferior vena cava embolectomy, (B) shows the sutured inferior vena cava, and (C) shows the liver incisal margin. Arrows in (A, B) figures indicate the position described above. (D-F) show the MRI reexamination after surgery. Arrows in (D-F) figures indicate the liver resection margin.
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The patient underwent right hemihepatectomy, retroperitoneal lymphadenectomy, right cardio-phrenic angle lymphadenectomy, and inferior vena cava embolectomy on December 10, 2019 (Figures 4A-C). T cells were observed in tumor margin and stromal. The patient underwent periodical MRI reexamination after surgery, which showed no recurrence in the coelom until March 3, 2021 (Figures 4D-F).